Interact CardioVasc Thorac Surg 2009;9:70-73. doi:10.1510/icvts.2009.202580
© 2009 European Association of Cardio-Thoracic Surgery
Institutional report - Thoracic oncologic |
The maximum standardized uptake values on positron emission tomography to predict the Noguchi classification and invasiveness in clinical stage IA adenocarcinoma measuring 2 cm or less in size
Ryo Maedaa,*,
Noritaka Isowaa,
Hideyuki Onumab,
Hiroshi Miurab,
Tomoya Haradac,
Hirokazu Tougec,
Hirokazu Tokuyasuc and
Yuji Kawasakic
a Division of Thoracic Surgery, Matsue Red Cross Hospital, 200 Horomachi, Matsue, Shimane 690-8506, Japan
b Division of Pathology, Matsue Red Cross Hospital, Shimane, Japan
c Division of Respiratory Medicine, Matsue Red Cross Hospital, Shimane, Japan
Received 12 January 2009;
received in revised form 3 March 2009;
accepted 23 March 2009
*Corresponding author. Tel.: +81-852-24-2111; fax: +81-852-31-9783.
E-mail address: ryomaedamatsue{at}yahoo.co.jp (R. Maeda).
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Abstract
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This study investigated whether the standardized uptake value (SUV) of the tumor correlated with the Noguchi classification and tumor invasiveness in patients with clinical stage IA adenocarcinoma  2 cm in size. Fifty-four patients that underwent a curative surgical resection for clinical stage IA adenocarcinoma 2 cm from April 2005 to December 2008 had integrated positron emission tomography (PET) – computed tomography (CT) with 18F-fluorodeoxyglucose (FDG) as part of the preoperative workup. The relationships between the maximum SUV (SUVmax) and Noguchi classification, pathological results of intratumoral lymphatic or vascular invasion of tumor cells, and pleural invasion were examined. In comparison to tumors with an SUVmax>1.0, tumors with an SUVmax1.0 were more frequently classified as Noguchi type A or B (P<0.0001). Tumors with an SUVmax>1.0 had more intratumoral lymphatic or vascular invasion of tumor cells and pleural invasion (P=0.0005 and P=0.0002). These results suggest that an SUVmax is an important predictor for the Noguchi classification and tumor invasiveness in patients with clinical stage IA adenocarcinoma 2 cm in size.
Key Words: Adenocarcinoma; FDG-PET; SUV; Thoracic surgery; Noguchi classification
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1. Introduction
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With the advance of diagnostic techniques, small lung tumors are detected and resected on more often [1, 2]. A lobectomy with systematic hilar and mediastinal lymph node dissection is the standard treatment for clinical stage IA non-small cell lung cancer (NSCLC), because a wedge resection or segmentectomy results in more frequent local or regional recurrence than a lobectomy [3]. However, some report successful results with limited surgery for clinical stage IA tumors 2 cm in size [4]. Noguchi et al. [5] classified small adenocarcinomas measuring 2 cm into six categories (type A–F). The Noguchi classification is useful with regard to evaluating the aggressive nature in individual patients. Types A and B are good candidates for a limited surgical resection such as a wedge resection. However, these criteria are based on postoperative pathological findings and could not have a strong impact on the choice of treatment.
Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is an increasingly available non-invasive test that has been shown to be useful for the evaluation of an indeterminate pulmonary nodule, the staging of mediastinal lymph nodes and the evaluation of local nodal and distant metastases [6–9]. FDG-PET measures the standardized uptake value (SUV) of a pulmonary mass, which quantifies the glucose avidity of the tumor. The FDG uptake correlates with the proliferative activity of tumors and is an independent prognostic factor in patients with lung cancer [7, 9].
The objective of this study was to assess whether the maximum SUV for body weight (SUVmax), which is less variable than the mean SUV [10], correlates with the Noguchi classification, intratumoral lymphatic or vascular invasion of tumor cells, and pleural invasion, which may affect tumor invasiveness in patients with peripheral small adenocarcinoma 2 cm in size.
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2. Materials and methods
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2.1. Patients
The database of the thoracic surgery department was searched for patients who underwent a lung resection for clinical stage IA adenocarcinoma 2.0 cm in size between April 2005 and December 2008, who had an FDG-PET/CT performed as part of the preoperative workup within one month of the resection. The clinical TNM stage was determined based on the findings of FDG-PET/CT and brain magnetic resonance imaging (MRI).
The medical records of each patient was examined with regard to age, sex, SUVmax, preoperative serum level of carcinoembryonic antigen (CEA), pathological stage, Noguchi classification, intratumoral vascular or lymphatic invasion of tumor cells, pleural invasion and lymph node metastasis.
2.2. PET FDG scanning
FDG-PET/CT scans were carried out on an integrated PET/CT scanner (Siemens, Biograph, LSO2). The patients were requested to fast for 4 h and then intravenously received 185 MBq (5 mCi) of FDG, followed by PET scanning after 60 min. Interactive reconstruction with CT attenuation correction was performed. In addition, chest CT scans were available for visual correlation. The SUVmax was established by drawing regions of interest on attenuation-corrected FDG-PET images around the tumor and calculated by the software within the PET/CT scanner using the following formula: maximum SUV=[C(µCi/ml)/ID(µCi)]/w, where C is defined as activity at a pixel within the tissue identified by regions of interest and ID is defined as the injected dose per kilogram of the patient's body weight (w). We adopted SUVmax in the present analysis because it is less variable than mean SUV in measuring.
2.3. Pathological examination
After localization and size measurement, the specimens were planed with a cryostat, serially sectioned (3–4 mm) and then were stained by standard hematoxylin and eosin. Elastica-van Gieson staining was routinely performed to identify tumor involvement in the intratumoral vessels or pleura. Experienced pathologists diagnosed the subtypes of the primary tumors according to the Noguchi classification. Pleural invasion was subdivided into p0 (no invasion), p1 (invasion into the visceral pleura), or p2 (invasion beyond the visceral pleura). The tumor stages were based on the TNM classification of the International Union Against Cancer [11]: p0–1 tumors were classified as T1, while p2 tumors were classified as T2.
2.4. Statistical analysis
Continuous variables were analyzed by Student's t-test, categorical variables by the  2-test using Stat View 5.0 (SAS Institute Inc, Cary, NC). The differences were considered to be statistically significant when the P-value was <0.05.
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3. Results
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3.1. Patient characteristics (Table 1)
The patient cohort consisted of 26 men and 28 women. Their age ranged from 43 to 85 years with a median of 70 years. The tumor size ranged from 0.7 cm to 2.0 cm (median 1.4 cm). The primary lesions were detected by a chest roentgenogram in 26 patients. The detection was determined by either a mass survey or private general check-up in 18 patients, a follow-up for other diseases in seven patients, and respiratory symptoms in one patient. The lesions in the other 28 patients were detected by chest CT performed in either a mass survey program or during a private general check-up. The surgical procedures were: 14 wedge resections; 13 segmentectomies with mediastinal lymph node dissection; 27 lobectomies. Systematic lymph node dissection was not performed in patients who underwent a wedge resection. A limited resection was performed in 27 patients considering the tumor size, the patients' high age or poor cardiopulmonary function. Informed consent regarding possible elevated risk of locoregional recurrence and inferior survival rate after limited resection was obtained from all patients whose cardiopulmonary function was adequate to a lobectomy. The Noguchi classification was A, B, C, D, E and F in 2, 16, 22, 3, 5 and 6 patients, respectively. Intratumoral lymphatic or vascular invasion of tumor cells and pleural invasion were seen in 15 and 12 patients, respectively. The stage of 14 patients who underwent a wedge resection was uncertain because the lymph nodes were not extirpated. Of the remaining 40 patients who underwent a lobectomy or segmentectomy with systematic hilar and mediastinal lymph node dissection, lymph node metastasis was seen in three patients. A summary of the patient characteristics and pathological characteristics is outlined in Table 1.
3.2. Correlation between the SUVmax and Noguchi classification (Tables 2 and 3)
Table 2 shows the value of SUVmax with relation to Noguchi type A–B and others. The value of SUVmax correlated statistically with the Noguchi classification (P=0.0004). Table 3 shows various SUVmax with relation to the Noguchi classification, intratumoral vascular or lymphatic invasion of tumor cells and pleural invasion. Medical records were compared between 20 adenocarcinomas with an SUVmax1.0 and 34 adenocarcinomas with an SUVmax>1.0.
3.3. Relationship between the SUVmax and patient characteristics, tumor size, serum level of CEA, tumor invasion into intratumoral vessels or pleura and the Noguchi classification (Table 4)
There was no significant difference between the two groups in the mean age, sex ratio, tumor size or serum levels of CEA. Noguchi type A–B was seen in 17 patients with an SUVmax 1.0, which was significantly more frequent (P<0.0001). No lymphatic or vascular invasion of the tumor cells was seen in the patients with an SUVmax 1.0, which was significantly less frequent (P=0.0005). No pleural invasion was seen in the patients with an SUVmax 1.0, which was also significantly less frequent (P=0.0002). Three patients with an SUVmax1.0 were diagnosed as Noguchi type C. These three patients underwent a segmentectomy with a mediastinal lymph node dissection, but no lymph node metastasis was found in any of the three patients.
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Table 4 Relationship between the SUVmax and the patient characteristics, tumor size, preoperative serum level of CEA, lymphatic vessel pleural invasion by tumor cells and the Noguchi classification
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4. Discussion
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In recent years, many small-sized NSCLCs have been detected as a result of the introduction of CT screening for lung cancer [1, 2]. Still, many surgeons advocate that systematic hilar and mediastinal lymph node dissection should be routinely used to secure complete local control of NSCLC, with a subsequent improvement in both survival and nodal staging, even if a patient's disease is classified as clinical stage IA, because even small NSCLC lesions have considerable potential for lymph node metastasis [3]. The accurate preoperative determination of the lack of necessity of systematic lymph node dissection in patients with clinical stage IA disease could have an effect on reducing surgical time, the degree of invasiveness, and perhaps the rapidity of patient recovery. Although clinically reliable predictors of pN0 disease would eliminate unnecessary lymph node dissection, no criteria permitting such a determination have yet been established. Several reports have evaluated the importance of ground-glass opacity (GGO) within tumors from CT findings because adenocarcinomas with GGO appearance are more frequently N0 stage [12, 13]. However, the criteria for defining GGO appearance on CT scans are subjective, and could potentially lead to an erroneous selection.
A major lung resection, either a lobectomy, or pneumonectomy has been the standard treatment for clinical stage IA NSCLC, based on the results of the LCSG trial [3]. A higher local or regional recurrence rate after a limited resection was observed even though a negative surgical margin was confirmed pathologically. This finding is probably due to tumor involvement of the intratumoral vessels, even for pathologic N0 disease, with the spread of tumor cells into the lymphatic vessels outside of the primary tumor, thus leading to a local recurrence [14]. However, some successful results regarding limited surgery for clinical stage IA tumors were published [4, 15]. Tsubota et al. [4] performed extended segmentectomies for 55 patients with peripheral cancers measuring <2 cm in size and only one patient locally recurred in whom N2 disease was not indicated during the operation. A limited surgical resection might have some advantages over a standard operation for selected patients. However, the preoperative patient selection for limited surgery is difficult.
Noguchi et al. [5] classified small adenocarcinomas into six categories (type A–F) and this classification indicated a favorable correlation with the biologically aggressive nature of the tumor. Type A and B are localized BAC with or without foci indicating a collapse of alveolar structures that are recognized to be non-invasive. Types D, E, and F are poorly differentiated, tubular, and papillary type, respectively. Pathological analyses reveal that all type A and B patients were N0, however, 25–56% of type D, E, and F patients indicated lymph node metastasis. If intraoperative frozen section differential diagnosis is reliably made with regard to their subtypes, a limited lung resection such as a wedge resection without mediastinal lymph node dissection can be indicated for patients with type A or B tumors. However, this differentiation is not as easy to diagnose as other conventional pathological factors, and an experienced pathologist, who is not available at every institute, is essential. Therefore, the preoperative criteria to define early minimally invasive cancers need to be established.
This study examined whether the SUVmax correlates with the Noguchi classification, intratumoral lymphatic or vascular invasion of tumor cells, and pleural invasion, which might affect tumor invasiveness in patients with small peripheral adenocarcinomas 2 cm in size. In the current study, 17 of 20 patients with an SUVmax1.0 were diagnosed as Noguchi type A or B and the remaining three patients were diagnosed as Noguchi type C. Neither lymphatic invasion, vascular invasion of the tumor cells nor pleural invasion was seen in any of the patients. In addition, three patients diagnosed as Noguchi type C underwent a segmentectomy with mediastinal lymph node dissection, but no lymph node metastasis was found in any of the three patients. In adenocarcinomas with an SUVmax1.0, a limited surgical resection may be indicated.
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5. Conclusion
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In patients with clinical stage IA small adenocarcinoma 2 cm, the SUVmax is considered to be an important predictor of predicting the Noguchi classification and tumor invasiveness.
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Abstract
1. Introduction