Clinical Imaging
Volume 36, Issue 1 , Pages 14-18, January 2012

Pulmonary metastases from colorectal cancer: imaging findings and growth rates at follow-up CT

  • Eun Young Kim

      Affiliations

    • Department of Radiology, Gachon University Gil Hospital, Incheon 405-760, Korea
    • ,
  • Jae-Ik Lee

      Affiliations

    • Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Hospital, Incheon 405-760, Korea
    • Corresponding Author InformationCorresponding author. Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Hospital, Incheon 405-760, Korea. Tel.: +82 32 460 3060; fax: +82 32 460 3065.
    • ,
  • Yon Mi Sung

      Affiliations

    • Department of Radiology, Gachon University Gil Hospital, Incheon 405-760, Korea
    • ,
  • So Hyun Cho

      Affiliations

    • Department of Radiology, Gachon University Gil Hospital, Incheon 405-760, Korea
    • ,
  • Dong Bok Shin

      Affiliations

    • Department of Internal Medicine, Gachon University Gil Hospital, Incheon 405-760, Korea
    • ,
  • Young Saing Kim

      Affiliations

    • Department of Internal Medicine, Gachon University Gil Hospital, Incheon 405-760, Korea
    • ,
  • Jeong-Heum Baek

      Affiliations

    • Department of Surgery, Gachon University Gil Hospital, Incheon 405-760, Korea

Received 1 April 2011; accepted 19 April 2011. published online 20 June 2011.

Article Outline

Abstract 

The objective of the study was to evaluate the computed tomographic (CT) features and growth rates of pulmonary metastases from colorectal cancer (CRC) on serial CT scans. The study included 17 patients (28 pulmonary metastases) who underwent metastasectomy from CRC. The characteristic CT features include well-defined round or oval nodules in the peripheral or subpleural/fissural lung with frequent feeding vessel sign. The mean tumor volume doubling time was calculated as 160 days. With these growth rates, short-term follow-up (i.e., 5–6 months) would be helpful.

Keywords: Pulmonary metastases, Metastasectomy, CT scan, Growth rate, Colorectal cancer

 

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1. Introduction 

Pulmonary metastases develop in 5%–15% of all colorectal cancer (CRC) patients, and performing resection of the pulmonary metastases from CRC has yielded 5-year survival rates ranging from 20% up to 60% in several large series, while patients with untreated metastatic disease have 5-year survival rates of less than 5% [1], [2].

The imaging features of the pulmonary metastases have been characterized, but the growth rates of pulmonary metastases from CRC have not been well established [3], [4], [5]. The purpose of this study was to evaluate the characteristics of the pulmonary metastases from CRC and to determine the tumor volume doubling times using volumetric measurement as determined on serial follow-up computed tomographic (CT) scans.

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2. Patients and methods 

2.1. Patients 

Between February 2004 and September 2010, 17 patients underwent surgical removal for 28 pulmonary metastases at our institution. The patients consisted of 5 men and 12 women, with ages ranging from 40 to 74 years (mean age, 57 years). Nine patients had rectal cancer, and eight patients had colon cancer. The initial pathological subtypes of the CRC were 4 well-differentiated adenocarcinomas, 12 moderately differentiated adenocarcinomas, and 1 poorly differentiated adenocarcinoma. At the time of diagnosis of CRC, three patients had hepatic metastases. All patients underwent surgery for the removal of CRC and adjuvant chemotherapy. These adjuvant treatments were finished within 6 months after surgery. After the operation for the CRC, the postoperative follow-up period ranged from 0 to 52 months (mean period, 20 months; median period, 24 months) until the detection of the pulmonary metastases, as determined by CT imaging. The prethoracotomy mean carcinoembryonic antigen level was 2.4 ng/ml (median, 2.1 ng/ml; range, 0.6–10.3 ng/ml). We evaluated the characteristics of the pulmonary metastases from CRC based on the medical records and CT scans.

Eight tumors of seven patients were excluded from the evaluation of the tumor volume doubling time because the previous chest CT scans were not available after the detection of pulmonary metastases from a CT scan. The remaining 20 tumors (11 patients) that underwent subsequent chest CT for pulmonary metastases were included for the evaluation of the tumor growth rates, which were determined on the serial preoperative chest CT scans. Our institutional review board approved this retrospective study and waived the requirement for informed patient consent.

2.2. CT scans 

After surgery, patients were followed up annually, and if they had any pulmonary nodules, they had a shorter chest CT schedule for the surveillance of pulmonary metastases. All the CT scans were performed with one of three helical scanners on a 16-slice, 64-slice or dual-source 64-slice CT (SOMATOM Sensation 16, SOMATOM Sensation 64, SOMATOM Definition, Siemens Healthcare, Germany). The parameters of the CT examinations were 140 kVp, 170 mA, 5-mm collimation and a 10-mm/s table feed with a 1-s rotation time, 5.0-mm slice thicknesses and 2.5–5.0-mm intervals. The postenhancement images were obtained within 30–40 s after the start of an injection of 120 ml nonionic iodinated contrast material (Ultravist 300 mg/ml, Schering AG, Berlin, Germany) administered through the antecubital vein at a rate of 3–4 ml/s.

2.3. Image analysis 

Two subspecialty-trained chest radiologists retrospectively reviewed the preoperative chest CT images by consensus. First, the characteristics of the pulmonary metastases, including the number, location (central, peripheral, subpleural or subfissural), size (longest diameter on the axial image), shape (round, ovoid, trapezoid), margin (smooth, lobulated, speculated) of the masses and the presence of internal necrosis, cavity and the feeding vessel sign. Second, the tumor volume doubling time was calculated with the volume of the pulmonary metastases evaluated from the serial postoperative CT scans. The tumor volume doubling time (DT) was calculated using the Schwartz equation [6]: DT=(T−To)×log 2/(log V−log Vο). T−Tο indicates the time interval between the two measurements, and Vο and V represent the tumor volumes at two points of measurement. For volumetric analysis, we reviewed all the CT images on a picture archiving and communication system (PACS; PathSpeed workstation, GE Medical Systems) workstation, and we measured the area of the metastatic tumors as determined at the follow-up CT examinations by manually tracing the contour of the tumor boundaries using a computer mouse (Fig. 1). The volume of a tumor was determined by adding the individual areas of each scan and multiplying this summation by the image thickness.

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  • Fig. 1. 

    A 65-year-old female with a pulmonary metastasis 30 months after an operation for descending colon cancer (well-differentiated adenocarcinoma, T2N0M0). (A) An initial CT scan shows a nodule just at the lateral aspect of the heart in the right middle lobe. The estimated tumor volume was 705 mm3. Metastasectomy was delayed due to the patient's refusal. (B) The nodule had increased in size on the follow-up chest CT after 434 days from the initial CT. The estimated tumor volume was 1540 mm3. With these volumetric data and time interval, the tumor volume doubling time was calculated as 385 days.

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3. Results 

3.1. CT findings of the pulmonary metastases from CRC 

Five pulmonary metastases were synchronous, which were seen at the time of diagnosing CRC, and 23 pulmonary metastases were metachronous, which were detected from the follow-up CT scans after surgical resection of CRC. Among the 23 metachronous pulmonary metastases, no patient showed recurrence within 6 months, 4 pulmonary metastases showed recurrence between 6 months to 1 year, 10 pulmonary metastases showed recurrence between 1 and 2 years and 7 pulmonary metastases showed recurrence between 2 and 3 years. The remaining two pulmonary metastases recurred 50 and 52 months after the CRC surgery.

Pulmonary metastases appeared as a solitary nodule (number of patients=10) or multiple nodules (number of patients=7, two metastases for four patients, three metastases for two patients and four metastases for one patient). The tumors ranged from 4 mm to 55 mm at the greatest diameter (mean diameter, 1.4 cm), and they were located in the right upper lobe (n=7), right middle lobe (n=3), right lower lobe (n=8), left upper lobe (n=3) and left lower lobe (n=7). They were distributed in the central (n=8), peripheral (n=16), subpleural or subfissural regions (n=4). They showed well-defined round (n=16), oval (n=10) or trapezoid (n=2) shape, and they showed smooth (n=19), lobulated (n=8) or lobulated and spiculated margin (n=1). The feeding vessel sign, cavity and internal necrosis were seen in 17, 4, and 3 tumors, respectively.

3.2. Calculated tumor doubling times 

For 20 tumors (11 patients) that underwent subsequent chest CT for pulmonary metastases, the mean interval between the occurrence of pulmonary metastases and the last follow-up before the metastasectomy was 231 days (range, 37–511 days; median time, 198 days). The mean volumes of the baseline tumors and the pulmonary metastases detected at the last follow-up were 433 mm3 (range, 40–2575 mm3; median, 268 mm3) and 1120 mm3 (range, 190–4395 mm3; median, 778 mm3), respectively. With these volumetric data, the mean tumor volume doubling time was calculated as 160 days (range, 30–385 days; median time, 153 days). In the prospective interpretation, 11 tumors were correctly diagnosed as pulmonary metastases, yet metastasectomy was delayed for 10 tumors for chemotherapy (nine tumors for palliative chemotherapy for CRC and one tumor for neoadjuvant chemotherapy for pulmonary metastasis). For tumors (10/20, 50%) that underwent chemotherapy, the mean tumor volume doubling time was 160 days (median tumor volume doubling time. 153 days; range. 30–385 days), and the remaining 10 tumors had 160 days as the mean tumor volume doubling time (median tumor volume doubling time, 150 days; range, 55–285 days), which was not significantly different (P=.85). One patient who had pulmonary metastases refused tumor removal. For the remaining nine tumors, we were unable to prospectively make an adequate diagnosis using the CT scans at the time of the first metastases; three tumors were missed, and six tumors were detected, but these patients were recommended for follow-up due to the small size of the lesions (Fig. 2, Fig. 3).

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  • Fig. 2. 

    A 61-year-old female with a pulmonary metastasis 23 months after an operation for sigmoid colon cancer (moderately differentiated adenocarcinoma, T3N1bM0). (A) An initial CT scan shows a small ovoid nodule (arrow) that is located along the bronchovascular bundle in the right lower lobe. The estimated tumor volume was 640 mm3. On the prospective interpretation, this nodule was missed. (B) The mass (arrow) increased in size on the follow-up chest CT (210 days from the initial CT). The estimated tumor volume was 1795 mm3. With these volumetric data and time interval, the tumor volume doubling time was calculated as 141 days.

  • View full-size image.
  • Fig. 3. 

    A 53-year-old female with a pulmonary metastasis 19 months after an operation for rectal cancer (well-differentiated adenocarcinoma, T3N2bM0). (A) An initial CT scan shows a small nodule (the longest diameter is 7 mm) in the right lower lobe. The estimated tumor volume was 215 mm3. The nodule was detected at that time, yet follow-up was recommended because of the small size of the nodule. (B) The nodule increased in size on the follow-up chest CT (182 days from the initial CT). The estimated tumor volume was 435 mm3. With these volumetric data and time interval, the tumor volume doubling time was calculated as 179 days.

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4. Discussion 

Colorectal cancer is the third most common cancer and the third leading cause of the cancer-related mortality estimated for 2010 in the United States [7]. More than half of the patients undergoing resection for CRC can be expected to have recurrence of the disease, and the most frequent sites of recurrence are the liver and the lung [8], [9]. While the role of chemotherapy together with surgery for pulmonary metastases has not yet been defined, surgery remains the mainstay for the treatment for patients with isolated pulmonary metastases according to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology [10].

Computed tomographic examinations are useful for making the diagnosis and for follow-up surveillance in patients with pulmonary metastases. Currently, the best method to assess pulmonary metastases is utilizing CT due to the detection of a larger number of lesions with a smaller diameter and the higher precision on measuring when compared to that of conventional radiography [11], [12]. Chest CT scans also provide an extremely accurate volume measurement. Especially for the small metastases, the volumetric evaluation is more exact than measurement of one- or two-longitudinal dimensions for the early diagnosis of metastases [13], [14], [15], [16]. Clinically, the growth rates have been calculated by taking tumor diameters during the observations separated by a time period and by determining the tumor doubling time [17]. Previous studies have obtained the tumor doubling time from the pulmonary metastases measured on chest radiographs [3], [6], [18], [19] or bidimensional measurement on chest CT [20], and the studies demonstrated a large variation.

We found widely variable tumor doubling times (range, 30–385 days), which might be due to diverse clinical situations (different initial staging, histopathology, and treatment for each patient, ±chemotherapy between the periods of two sequential chest CT scans). However, there was no significant difference in the tumor volume growth rates between the group that underwent chemotherapy and the group that did not. According to Chojniak and Younes [20], the pulmonary metastases from a variety of primary tumors (including six patients with CRC) showed variable doubling times, even for the patients who did not undergo chemotherapy or radiation therapy. Approximately half of the metastases showed an unaltered size (30%) or a reduction (11%) in the size, and the tumor doubling time for pulmonary metastases that showed progression also revealed widely variable doubling times that ranged from 22 to 930 days (mean tumor volume doubling time, 118 days).

We revealed short tumor volume doubling times (mean tumor volume doubling time, 160 days), and this suggests that a short follow-up interval of about 5–6 months for early detection after CRC operation could improve the likelihood of making an early diagnosis of pulmonary metastases [21], [22], [23], [24], [25]. In fact, in half of the cases, we were unable to prospectively make an adequate diagnosis at the first time of metastases. The reasons for the prospectively missed three cases were as follows: a relatively small size tumor that was not easy to detect (the volume of tumors were 0.1 cm3, 0.4 cm3 and 0.6 cm3, respectively) with the location of the tumors being very close to the bronchovascular bundle (n=2), which made detection difficult (Fig. 2). Thus, radiologists should pay special attention to detect small nodules that are located along the bronchovascular bundles, and the lesions should be followed up with a shorter period (i.e., 5–6 months).

Our study has several limitations. First, this study was performed in a retrospective manner, so not all the patients were followed up at regular intervals using the same CT machines. Second, the perioperative management of the patients was not uniform in terms of (neo) adjuvant chemotherapy. However, this limitation is unavoidable in a routine clinical setting, and it more accurately reflects the practical situation. Third, we evaluated only the cases of surgically confirmed pulmonary metastases, and we could not be ‘blind’ to this fact. Finally, the number of included patients was small because this study was performed at a single institution. Particularly, the mean tumor volume doubling time calculated for the small number of tumors could be limited.

In conclusion, pulmonary metastases were seen as well-defined round or oval nodules that were located in the periphery or the subpleural or subfissural portions of both lower lobes. The feeding vessel sign was also frequently seen. The mean tumor volume doubling time was calculated as 160 days with a variable range (30–385 days) in a practical clinical setting of diverse stages and treatments, so short-term (i.e., 5–6 months) follow-up would be helpful for the surveillance of pulmonary metastases from CRC.

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References 

  1. Seymour MT, Stenning SP, Cassidy J. Attitudes and practice in the management of metastatic colorectal cancer in Britain. Colorectal Cancer Working Party of the UK Medical Research Council. Clin Oncol (R Coll Radiol). 1997;9(4):248–251
  2. Simmonds PC. Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group. BMJ. 2000;321(7260):531–535
  3. Blomqvist C, Wiklund T, Tarkkanen M, Elomaa I, Virolainen M. Measurement of growth rate of lung metastases in 21 patients with bone or soft-tissue sarcoma. Br J Cancer. 1993;68(2):414–417
  4. Hirakata K, Nakata H, Nakagawa T. CT of pulmonary metastases with pathological correlation. Semin Ultrasound CT MR. 1995;16(5):379–394
  5. Murata K, Takahashi M, Mori M, et al. Pulmonary metastatic nodules: CT-pathologic correlation. Radiology. 1992;182(2):331–335
  6. Schwartz M. A biomathematical approach to clinical tumor growth. Cancer. 1961;14:1272–1294
  7. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300
  8. August DA, Ottow RT, Sugarbaker PH. Clinical perspective of human colorectal cancer metastasis. Cancer Metastasis Rev. 1984;3(4):303–324
  9. McCormack PM, Burt ME, Bains MS, Martini N, Rusch VW, Ginsberg RJ. Lung resection for colorectal metastases. 10-year results. Arch Surg. 1992;127(12):1403–1406
  10. Pfannschmidt J, Dienemann H, Hoffmann H. Surgical resection of pulmonary metastases from colorectal cancer: a systematic review of published series. Ann Thorac Surg. 2007;84(1):324–338
  11. Davis SD. CT evaluation for pulmonary metastases in patients with extrathoracic malignancy. Radiology. 1991;180(1):1–12
  12. Peuchot M, Libshitz HI. Pulmonary metastatic disease: radiologic–surgical correlation. Radiology. 1987;164(3):719–722
  13. deSantos LA, Ginaldi S, Wallace S. Computed tomography in liposarcoma. Cancer. 1981;47(1):46–54
  14. Gupta AK, Cohan RH, Francis IR, Sondak VK, Korobkin M. CT of recurrent retroperitoneal sarcomas. AJR Am J Roentgenol. 2000;174(4):1025–1030
  15. Nawaratne S, Fabiny R, Brien JE, et al. Accuracy of volume measurement using helical CT. J Comput Assist Tomogr. 1997;21(3):481–486
  16. Neifeld JP, Walsh JW, Lawrence W. Computed tomography in the management of soft tissue tumors. Surg Gynecol Obstet. 1982;155(4):535–540
  17. Collins VP, Loeffler RK, Tivey H. Observations on growth rates of human tumors. Am J Roentgenol Radium Ther Nucl Med. 1956;76(5):988–1000
  18. Lokich J, D'Orsi C, Smith E, Gero M. Tumor growth and regression rates relative to tumor size: a clinical study of metastatic pulmonary nodules. Cancer. 1981;47(6):1415–1420
  19. Spratt JS, Meyer JS, Spratt JA. Rates of growth of human neoplasms: part II. J Surg Oncol. 1996;61(1):68–83
  20. Chojniak R, Younes RN. Pulmonary metastases tumor doubling time: assessment by computed tomography. Am J Clin Oncol. 2003;26(4):374–377
  21. Kubota K, Ina H, Okada Y, Irie T. Growth rate of primary single hepatocellular carcinoma: determining optimal screening interval with contrast enhanced computed tomography. Dig Dis Sci. 2003;48(3):581–586
  22. Taouli B, Goh JS, Lu Y, et al. Growth rate of hepatocellular carcinoma: evaluation with serial computed tomography or magnetic resonance imaging. J Comput Assist Tomogr. 2005;29(4):425–429
  23. Bautista N, Su W, O'Connell TX. Retroperitoneal soft-tissue sarcomas: prognosis and treatment of primary and recurrent disease. Am Surg. 2000;66(9):832–836
  24. Jaques DP, Coit DG, Hajdu SI, Brennan MF. Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum. Ann Surg. 1990;212(1):51–59
  25. Sato T, Yamaguchi T, Azekura K, et al. Repeated resection for intra-abdominal and retroperitoneal liposarcomas: long-term experience in a single cancer center in Japan. Int Surg. 2006;91(5):267–271

PII: S0899-7071(11)00097-0

doi:10.1016/j.clinimag.2011.04.018

Clinical Imaging
Volume 36, Issue 1 , Pages 14-18, January 2012

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