Small Peripheral Lung Cancer Research Articles

CALGB 140503: A Randomized Phase III Trial of Lobectomy versus Sublobar Resection for Small (< 2cm) Peripheral Non-Small Cell Lung Cancer

"CALGB 140503: A Randomized Phase III Trial of Lobectomy versus Sublobar Resection for Small (< 2cm) Peripheral Non-Small Cell Lung Cancer." Oncology Issues, 23(6), pp. 20–21 Additional informationNotes on contributorsNicole FoxNicole Fox, MD, is surgical resident, Christiana Care in Newark, Del. Thomas Bauer, MD is chief of Thoracic Surgery, Helen F. Graham Cancer Center at Christiana Care; clinical assistant professor of surgery, Jefferson Medical College; adjunct professor of biologic sciences, University of Delaware; and co-principal investigator of CALGB 140503.Thomas BauerNicole Fox, MD, is surgical resident, Christiana Care in Newark, Del. Thomas Bauer, MD is chief of Thoracic Surgery, Helen F. Graham Cancer Center at Christiana Care; clinical assistant professor of surgery, Jefferson Medical College; adjunct professor of biologic sciences, University of Delaware; and co-principal investigator of CALGB 140503.

Diagnosis and treatment of small peripheral lung cancer

周围型小肺癌的构成比约占同期肺癌的10%左右.经手术切除5年生存率超过80%.Noguchi组织学分型的A型和B型在胸部CT上常常表现为磨玻璃影(GGO),5年生存率可达97.3%.即使是≤2 cm的病灶,仍可伴有10%～30%的淋巴结转移.标准的治疗方法应为肺叶切除加系统纵隔淋巴结清除.除非病灶≤1 cm且在胸部薄层高分辨CT上显示明显的GGO,则可考虑行病灶局部切除。

Neural network-based computer-aided diagnosis in distinguishing malignant from benign solitary pulmonary nodules by computed tomography

Computer-aided diagnosis (CAD) of lung cancer is the subject of many current researches. Statistical methods and artificial neural networks have been applied to more quantitatively characterize solitary pulmonary nodules (SPNs). In this study, we developed a CAD scheme based on an artificial neural network to distinguish malignant from benign SPNs on thin-section computed tomography (CT) images, and investigated how the CAD scheme can help radiologists with different levels of experience make diagnostic decisions. Two hundred thin-section CT images of SPNs with proven diagnoses (135 small peripheral lung cancers and 65 benign nodules) were analyzed. Three clinical features and nine CT signs of each case were studied by radiologists, and the indices of qualitative diagnosis were quantified. One hundred and forty nodules were selected randomly to form training samples, on which the neural network model was built. The remaining 60 nodules, forming test samples, were presented to 9 radiologists with 3 - 20 years of clinical experience, accompanied by standard reference images. The radiologists were asked to determine whether a nodule was malignant or benign first without and then with CAD output. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. CAD outputs on test samples had higher agreement with pathological diagnoses (Kappa = 0.841, P < 0.001). Compared with diagnostic results without CAD output, the average area under the ROC curve with CAD output was 0.96 (P < 0.001) for junior radiologists, 0.94 (P = 0.014) for secondary radiologists and 0.96 (P = 0.221) for senior radiologists, respectively. The differences in diagnostic performance with CAD output among the three levels of radiologists were not statistically significant (P = 0.584, 0.920 and 0.707, respectively). This CAD scheme based on an artificial neural network could improve diagnostic performance and assist radiologists in distinguishing malignant from benign SPNs on thin-section CT images.

The CT investigation of lobulation sign in solitary pulmonary nodules

目的 探讨CT的分叶征表现在肺内孤立结节影像诊断的价值以及CT多平面重组(MPR)对此征检出的意义.方法 观察病理证实的周围型小肺癌137例及良性肺内结节45例,将结节的边缘分为4型.对28例肺癌、22例良性结节行MPR,考察其显示分叶征的作用.引入可能性比值(likelihood ratios,LR)以量化良恶性病变在形态学上存在重叠的表现.结果 Ⅰ型边缘结节对良性病变的特异性为83.3%(20/24),敏感性为44.4%(20/45).Ⅳ型边缘结节对周围型小肺癌的特异性为97.6%(83/85),敏感性为60.7%(83/137).表明Ⅰ型边缘是良性病变的特点;而Ⅳ型边缘是恶性病变的特征.Ⅳ型边缘的结节恶性病变在MPR重组图像上的检出率为64.3%(18/28),与横断面扫描差异有统计学意义(P＜0.01).结论 分叶征对肺内孤立结节的诊断有价值,MPR配合横断面薄层图像有助于提高该征的检出率。

High-Dose-Rate Brachytherapy for Small-Sized Peripherally Located Lung Cancer

The demand for minimally invasive therapies is increasing in the treatment of small peripheral non-small cell lung cancer (NSCLC). Twelve patients with T1-2 N0 M0 peripheral NSCLC were treated by high-dose-rate brachytherapy with (192)Ir radioactive source. A (192)Ir source was introduced into the tumors percutaneously in five patients (percutaneous brachytherapy) or transbronchially in seven patients (transbronchial brachytherapy). Whereas irradiation was performed with a single fraction of 20 Gy in percutaneous brachytherapy, it was hypofractionated from 5 x 5 Gy to 2 x 12.5 Gy in transbronchial brachytherapy. Complications were generally mild in all patients, although focal radiation pneumonitis was observed in most patients. Primary recurrence occurred in three patients, including one with a T2 tumor and one treated by brachytherapy as a salvage treatment for recurrence after conformal radiotherapy. When brachytherapy is evaluated as a primary treatment for T1 N0 M0 NSCLC, local control rate is 88.9% and estimated 5-year survival rate is between 60% and 70%. Brachytherapy has a potential to be a method to treat peripheral T1 N0 M0 NSCLC.

Percutaneous CT-guided fine needle aspiration for lung cancer smaller than 2 cm and revealed by ground-glass opacity at CT

The purpose of this retrospective study was to evaluate the value of preoperative percutaneous CT-guided fine needle aspiration biopsy (CTNB) for peripheral lung cancers less than 2 cm in size, especially in cases showing of ground-glass opacities (GGO). From 1999 to 2002, 151 small lung cancers were resected in Tokyo Medical University Hospital. Among them, 96 patients (63.6%) in whom the lesions were located in the outer half of the lung field underwent CTNB in order to obtain a preoperative diagnosis. The factors influencing the diagnostic yield were analyzed. The overall diagnostic yield of CTNB was 64.6%: 48.5% for lesions smaller than 10 mm, 62.5% for those 11-15 mm, and 83.9% for those 16-20 mm, respectively. The diagnostic yield in GGO-dominant lesions (GGO ratio < 50%) and solid-dominant lesions (GGO ratio < 50%) were 51.2% and 75.6% (p = 0.018). In the GGO-dominant group, the diagnostic yields were 35.2% for lesions smaller than 10 mm, 50.0% for those 11-15 mm, and 80.0% for those 16-20 mm. In the solid-dominant group, diagnostic yield was 62.5% for cases smaller than 10 mm, 75% for 11-15 mm and 85.7% for 16-20 mm, respectively. Satisfactory diagnostic yield (>80%) was obtained by CTNB in cases larger than 15 mm. CTNB is a useful diagnostic modality for peripheral small lung cancers; however, for GGO-dominant lesions, the preoperative diagnostic yield is not significantly better than for solid-dominant lesions.

PD-141 Feasibility of limited resection for peripheral small lung cancer with regard to CT image and tumor differentiation

PD-141 Feasibility of limited resection for peripheral small lung cancer with regard to CT image and tumor differentiation

O-175 Limited resection for small peripheral lung cancer

O-175 Limited resection for small peripheral lung cancer

Objective radiologic analysis of ground-glass opacity aimed at curative limited resection for small peripheral non-small cell lung cancer

The aim of this study was to evaluate the efficacy of the objective radiologic analysis of high-resolution computed tomographic images of small peripheral non-small cell lung cancer and to select the candidates for curative limited resection. High-resolution computed tomographic images of 146 surgically resected T1 N0 M0 peripheral non-small cell lung cancers were analyzed by using National Institutes of Health image software and classified on the basis of the percentage of ground-glass opacity within the tumor. Eighty-seven percent of tumors with ground-glass opacity ratios of 90% to 100% (type I) were diagnosed as noninvasive bronchioloalveolar carcinoma, whereas 55.6% of tumors with ground-glass opacity ratios of 50% to 89% (type II) consisted of adenocarcinoma. Tumors with ground-glass opacity ratios of 50% or more (type I/II) had no nodal involvement, whereas nodal metastases were identified in 20.0% of tumors with ground-glass opacity ratios of 10% to 49% (type III) and 24.4% of tumors with ground-glass opacity ratios of less than 10% (type IV). No tumors with ground-glass opacity ratios of 50% or more showed vessel infiltration, except for one lesion with a ground-glass opacity ratio of 50%. The 3-year disease-free survival was 97.7% for type I/II, 86.1% for type III, and 78.5% for type IV tumors. The objective quantitative radiologic analysis with National Institutes of Health image software exhibited a good correlation with the histologic classification, pathologic invasiveness, and postoperative outcome of small peripheral lung cancer. Patients with tumors that have ground-glass opacity ratios of greater than 50% are considered to be possible candidates for limited pulmonary resection.

New Method of Visualizing Lymphatics in Lung Cancer Patients by Multidetector Computed Tomography

The aim of the present study was to investigate the safety and acceptability of a new method of visualizing lymphatics, including sentinel lymph nodes (SNs), in lung cancer patients using multidetector computed tomography (MDCT). Images were obtained using an MDCT scanner (Asteion Multi 4 Detector-Row; Toshiba) at 1, 2, and 3 minutes after percutaneous injection of 1 mL contrast medium (iohexol) near the tumor in 15 patients with small peripheral lung cancers (cT1N0M0). A lymph node was confirmed to be an SN if the attenuation was more than 30 Hounsfield units greater on postcontrast images than on precontrast images. All patients underwent surgery, and definitive lymph node staging was assessed. The procedure was performed safely in all patients without significant complications. Lymphatic ducts or lymph nodes were visualized in all 15 patients. The SN was identified in 14 of 15 patients (93.3%) at lymph node 14 in 4 patients, lymph node 13 in 7, lymph node 12 in 6, and lymph node 6 in 1. In 1 remaining patient, the lymphatic duct running from the tumor toward the pleura was visualized. Lymphatics were visualized by this method in all patients without significant complications. This method should be useful not only to detect the SNs but to visualize pathways other than through the hilar lymph nodes.

Intentional limited resection for small peripheral lung cancer based on intraoperative pathologic exploration

The aim of this study was to assess the adequacy of our intentional limited resection for small peripheral lung cancer based on intraoperative pathologic exploration. Patients who had stage IA non-small cell lung cancer (NSCLC) with a maximum tumor diameter of 2 cm or less were candidates for limited resection. If bronchioloalveolar carcinoma (BAC) was suspected on computed tomography and intraoperative pathologic exploration revealed the lesion as BAC without foci of active fibroblastic proliferation (Noguchi type A and B), wedge resection was performed. If the tumor was not suspected of being Noguchi type A or B, extended segmentectomy with intraoperative lymph node exploration was performed. Limited resection was performed in 34 patients, wedge resection in 14, and extended segmentectomy in 20. The median follow-up period after wedge resection was 36 months, and all patients are alive with no signs of recurrence. The median follow-up period after extended segmentectomy was 54 months. No local recurrences were found, but distant metastasis was diagnosed in one patient. The 5-year survival rate after extended segmentectomy was 93%. In the same period, lobectomy was performed in 57 patients with stage IA NSCLC with a maximum tumor diameter of 2 cm or less, and the 5-year survival rate was 84%. There were no significant differences in 5-year survival between extended segmentectomy and lobectomy. Careful selection of patients based on high-resolution computed tomography findings and intraoperative pathologic exploration makes intentional limited resection an acceptable option for the treatment of small peripheral NSCLC.

High-resolution CT Findings of Primary Site in Small Peripheral Lung Cancer with Mediastinal Metastases to Normal-sized Lymph Nodes

PURPOSE: To preserve pulmonary function in lung cancer patients, the video assistant thoracic surgery and conformal radiotherapy are developing. The accurate nodal staging is essential in these treatments. Although FDG-PET is the most accurate diagnostic procedure, there are some false-positive and false–negative diagnoses. We hypothesized that some pathological features of lymphatics are revealed on HRCT in patients with mediastinal metastases to normal-size lymph nodes. The purpose of this study is to evaluate whether it is useful to assess CT appearances of the primary site of lung cancer in the nodal staging.

Video-assisted thoracoscopic surgery (VATS) segmentectomy for small peripheral lung cancer tumors: intermediate results

We investigated the feasibility and suitability of video-assisted thoracoscopic surgery (VATS) segmentectomy for curing selected non-small cell lung cancer (NSCLC) with this less invasive technique. We performed VATS segmentectomy for small (< 20 mm) peripherally located tumors and pathologically confirmed lobar lymph node-negative disease by frozen-section examination during surgery. Of the 34 patients who underwent this limited resection, 22 were treated with complete hilar and mediastinal lymph node dissection (intentional group), whereas 12 patients who were deemed to be high risk in their toleration for lobectomy underwent VATS segmentectomy with incomplete hilar and mediastinal lymph node dissection (compromised group). The surgical and clinical parameters were evaluated and compared with those of segmentectomy under standard thoracotomy to evaluate the technical feasibility of VATS segmentectomy. We found that VATS segmentectomy could be performed safely with a nil mortality rate and acceptably low morbidity. The mean period of observation was relatively short at 656.7 +/- 572.1 and 783.4 +/- 535.8 days in the intentional and compromised groups, respectively. At the time of writing, all intentional patients remain alive and free of recurrence. There were two cases of non-cancer-related death in the compromised group. Clinical data indicated that VATS segmentectomy caused the same number or fewer surgical insults compared with segmentectomy under standard thoracotomy. The present results are intermediate only; the rate of long-term survival and the advantages of the less invasive procedure still need further investigation. Nevertheless, we believe that VATS segmentectomy with complete lymph node dissection is a reasonable treatment option for selected patients with small peripheral NSCLC.

Detection and diagnosis of small peripheral lung cancers less than 15mm in diameter

OBJECTIVE To assess the value of chest X-ray film, conventional CT (CCT), Spiral CT (SCT) and high resolution CT (HRCT) for detection and diagnosis of small peripheral lung cancers less than 15 mm in diameter. METHODS Chest X-ray film, CCT, SCT and HRCT were taken in 59 cases of peripheral lung cancers less than 15 mm in diameter confirmed by pathological examination following an operation. The value of these procedures for diagnosis was analyzed retrospectively. RESULTS In 47% of chest X-ray films and 17% of CCT, small lung cancers were not detected. However no tumor escaped detection by SCT. HRCT was superior for showing density and detailed image signs compared to chest films and CCT. The HRCT features of small peripheral lung cancers were quite different from those of larger peripheral lung cancers. CONCLUSION The SCT is the best method for detection, and HRCT for diagnosis of small peripheral lung cancers less than 15 mm in diameter. CT guided percutaneous transthoracic needle biopsy should be advocated.

The demonstration of nodule notch due to pleural indentation in mulitplanar reconstruction

目的 认识胸膜凹陷相关结节切迹(NNPI)的征象.探讨CT多平面重建(MPR)配合多层螺旋CT对恶性胸膜凹陷的诊断价值.方法 (1)观察病理证实的周围型小肺癌(SPLC)91例,良性小结节59例.9例SPLC、2例良性结节术后用改良Heitzman法充气固定肺叶制成病理大切片.比较分析良、恶性胸膜凹陷对照组及充气标本扫描和病理切片.(2)对恶性胸膜凹陷20例、良性12例行CT MPR,观察MPR显示NNPI的作用.结果 (1)NNPI是指胸膜线影进入结节内部,于结节表面形成切迹改变.此征对恶性胸膜凹陷特异度为96.5%.(2)恶性胸膜凹陷切迹在MPR的检出率为80%,与横断面扫描之间差异有显著意义(χ2=13.205,P<0.05).结论 NNPI对于恶性胸膜凹陷有高特异性诊断价值.MPR配合多层螺旋CT能提高此征检出率。

Bronchoscopically undiagnosed small peripheral lung tumors

Small peripheral lung cancers (2 cm or less maximum diameter) are often surgically resected, and the survival rate of those patients has been reported to be significantly higher than that of patients with tumors 2.1 cm or more in diameter. We evaluated the status of these small tumors diagnosed during surgery, following unsuccessful transbronchial biopsy procedures. In a retrospective study, 84 consecutive patients, with a maximum diameter of 2 cm or less on chest computed tomography, were enrolled. All underwent surgery for diagnosis. Video-assisted thoracoscopic surgery was performed in 49 cases (58%), Video-assisted thoracoscopic surgery+mini-thoracotomy in ten cases (12%), and an open lung biopsy in 25 cases (30%). Primary lung cancer was found in 40 cases (48%), metastatic lung tumors in three cases (3%), and benign lung tumors in 41 cases (49%). Among the 40 primary lung cancer cases, adenocarcinoma was in 38, squamous cell carcinoma was in one, and small cell carcinoma was in one. The rate of stage IA was 90%. Surgical excision of undiagnosed small peripheral nodules without waiting is necessary if transbronchial biopsy diagnosis is unsuccessful, because of the high rate of stage IA non-small cell lung cancer.

Effect of radioisotope sentinel node mapping in patients with cT1 N0 M0 lung cancer

Background Application of the sentinel node concept to lung cancer is still controversial. Patients with peripheral small lung cancers would gain the most benefit from this concept, if it were valid. We sought to determine whether it is possible to choose between limited lymph node sampling and systematic lymphadenectomy from the distribution of sentinel lymph nodes in patients with node-negative disease on the basis of imaging. Methods Sixty-five consecutive patients with cT1 N0 M0 non–small cell lung cancer were enrolled. A radioisotope tracer (4 mCi of technetium-99m tin colloid, 2.0 mL) was injected in the vicinity of the tumor before surgical intervention with computed tomographic guidance. The radioactivity of each resected lymph node was measured separately with a hand-held gamma probe after complete tumor resection. Sentinel nodes were identified, and the accuracy of sentinel node mapping was examined. Whether the location of the sentinel node depended on the site of the primary tumor was also examined. Results Of the 65 patients, 3 were excluded because of the final pathologic results. Successful radionuclide migration occurred in 39 (62.9%) of the 62 patients. There was 1 (2.6%) false-negative result among 39 patients with a sentinel node, and therefore the sensitivity was 90%, and the specificity was 100%. The most common sentinel lymph nodes were at level 12 (46.7%), followed by level 11 (18.3%), the mediastinum (16.7%), and level 10 (11.7%). Conclusion The sentinel node concept is valid in patients with cT1 N0 M0 lung cancer. The lobar lymph nodes were identified as sentinel nodes more frequently than other lymph nodes. We need to make further efforts to increase the sentinel node identification rate. However, we believe that if sentinel nodes are identified, sentinel node mapping can allow the accurate intraoperative diagnosis of pathologic N0 status in patients with cT1 N0 M0 lung cancer.

Improvement of three-dimensional treatment planning models of small lung targets using high-speed multi-slice computed tomographic imaging

Purpose : To improve the reliability of the patient model and reduce treatment volume by acquiring multi-slice computed tomographic (CT) data with the patients’ single holding of breath at normal inhalation and exhalation. Methods and Materials : Seven patients with nine small peripheral lung cancer tumors underwent CT scanning under three respiration conditions using multi-slice CT: free breathing (FB), shallow inspiration (SI), and shallow expiration (SE). To compare the treatment plan created using the two-respiratory-phase images (SI + SE) with the plans created using only SE images or using only FB images, we attempted to calculate the true dosimetric characteristics for three-dimensional treatment planning taking respiratory movement into consideration. Minimum dose to the gross tumor volume (GTV) and ipsilateral lung dose-volume histogram (DVH) were calculated for the inhalation and exhalation positions of shallow breathing. Results : There was no significant difference between minimum doses of the GTV in the three treatment plans when using anteroposterior/posteroanterior parallel-opposed fields. However, there was a significant difference between the minimum doses of the GTV in the two-phase treatment plan and the minimum dose in the other treatment plans when using the four-field technique, consisting of shaped anterior, posterior, right and left lateral fields ( p = 0.03, 0.04). Comparison of the percent volume of ipsilateral lung receiving a dose exceeding 20 Gy (V 20) based on inhalation and exhalation CT data revealed that the V 20 of the two-phase plan was the smallest of the three treatment planning fields ( p < 0.001). Conclusion : Two-phase planning using multi-slice CT provides an immediate reduction in the amount of normal tissue treated and improved reliability of patient data for DVH modeling.

Induced sputum in the diagnosis of peripheral lung cancer not visible endoscopically

The diagnosis of small peripheral lung cancer is difficult to achieve by non-invasive methods. We hypothesized that in these patients induced sputum might increase the diagnostic yield over spontaneous sputum, representing a good diagnostic alternative in selected patients. We prospectively evaluated 60 patients with peripheral lung lesions and normal bronchoscopic evaluation. Six samples of sputum (three spontaneous and three induced with nebulization of hypertonic saline) before bronchoscopy and six samples of sputum after bronchoscopy (three spontaneous and three induced) were obtained in each subject. Forty-two out of the 60 patients included were finally diagnosed with lung cancer. Eighteen patients were diagnosed with different benign conditions of the lung. Overall, malignant cells in sputum were observed in 21 patients and in all but one, the final diagnosis of lung cancer was achieved. Only one patient with a pseudoinflammatory tumour of the lung had a false-positive result in one spontaneous sputum sample. The diagnosis of lung cancer was obtained in 18 patients with the induced sputum (43%) and in 14 patients with spontaneous sputum (31%) (P=NS). Samples of induced sputum were more adequate for cytological analysis than samples of spontaneous sputum (P<0·0001). Of 13 patients with peripheral lung neoplasms of 2 cm or less in diameter, five were diagnosed using induced sputum (38%) and only one using spontaneous sputum (8%) (P<0·05). In conclusion, induced sputum is a valuable technique for the diagnosis of peripheral lung cancer. Induced sputum gives better quality specimens and better diagnostic yield in small lesions than the spontaneous sputum and may be indicated in selected patients with disseminated disease, inoperability or severe co-morbilities.

Visibility of small peripheral lung cancers on chest radiographs: influence of densitometric parameters, CT values and tumour type.

The purpose of this study was to determine the effects of tumour density and tumour type on the visibility of small peripheral lung cancers on chest radiographs. We retrospectively evaluated the visibility of 63 small (< or = 20 mm) peripheral lung cancers on chest radiographs. 48 (76%) were detected in our low dose CT screening for lung cancer and 15 (24%) in routine clinical examination. Analysis was based on tumour optical contrast, gradient at the tumour margin, CT values and tumour type. There were 31 (49%) visible cancers and 32 (51%) invisible cancers on chest radiographs. Visible tumours had an optical density of 0.1-0.3 OD and a gradient of 0.03-0.11 OD mm-1. The mean size of visible tumour (14.3 mm) was larger than that of invisible tumour (11.1 mm; p < 0.001). The mean CT value (-140 HU) of visible tumour was higher than that of invisible tumour (-490 HU; p < 0.001). The detection rates of adenocarcinomas with lepidic growth (0% for type A, 29% for type B and 68% for type C) were less than those with hilic growth (100% for types D-F). All squamous and small cell carcinomas with hilic growth were visible on chest radiographs, but the numbers of each were small. In summary, tumour type influenced the contrast, gradient, CT values and margin of the tumour. Small adenocarcinomas with a lepidic tumour growth were less well seen on chest radiographs compared with small lung cancers with hilic tumour growth.