Fluorescence bronchoscopy for early detection of lung cancer: a clinical perspective.

The conventional method of bronchoscopy has only a 30% sensitivity to detect early stage cancer in the central airways. For patients with positive sputum cytology who clearly harbor early cancers, repeat and lengthy sessions of bronchoscopies are required for accurate localization of these lesions. This leads to a significant delay in obtaining the diagnosis, postponing an appropriate treatment and reduces the chance for cure. There are valid reasons for improving the detection rate of early stage lung cancers. The number of individuals at risk forms a large population, the outcome of patients treated with early stage cancer has been shown to be better and bronchoscopic treatments, e.g. photodynamic therapy and electrocautery, are currently alternatives for surgical resection. Finding more early stage cancers by screening the population at risk and accurate staging to enable treatment at the earliest stage feasible, may improve the dismal prognosis of many patients. This article deals with the clinical background and current problems in early detection of lung cancer and discusses our expectations regarding new developments in bronchoscopy for early detection, accurate staging and treatment of lung cancer.     

Bronchoscopic treatment of patients with intraluminal microinvasive radiographically occult lung cancer not eligible for surgical resection: a follow-up study

Bronchoscopic treatment (BT) has a curative potential for patients with intraluminal microinvasive radiographically occult lung cancer (ROLC). We report the long-term follow-up in a group of 32 patients, ineligible for surgery, in whom ROLC was diagnosed and treated with BT. Tumors were strictly 相似文献   

Management of central airway obstruction

The efficacy of interventional pulmonology for palliation of patients with central airway obstruction has been established, and its curative potential for early cancer has raised great interest in current screening programs. The success of endoscopic strategies for palliation and treatment with curative intent strongly depends on the diligent identification of the various factors in lung cancer management, including full comprehension of the limits and potential of each particular technique. In the palliative setting of alleviating central airway obstruction, laser resection, electrocautery, argon plasma coagulation, and stenting are techniques that can provide immediate relief, in contrast with cryotherapy, brachytherapy, and photodynamic therapy, which have delayed effects. With curative intent, intraluminal techniques that easily coagulate early-stage cancer lesions will increase the implementation of interventional pulmonology for benign and relatively benign diseases, as well as early cancer lesions and its precursors at their earliest stage of disease.     

Laser and photodynamic therapy of esophageal cancer.

With proper selection of patients with non-operative esophageal cancer, palliative therapy with Nd:YAG laser enhances the quality of life by improving the patient's ability to swallow soft or solid food. Also, the use of non-thermal laser light to initiate the process of photodynamic therapy (PDT) is an additional laser technique that appears effective, not just in palliative treatment, but also in the cure of early esophageal cancer. For PDT, considerable work will be necessary to provide standard techniques in tumor staging, light and drug delivery and in light dosimetry. Ultimately, palliative and curative therapy of esophageal cancer will most likely incorporate multiple modalities, including surgery, radiation, chemotherapy, stents, laser and other thermal modalities, photodynamic therapy, and combinations of these methods.     

Surgical strategies in the therapy of non-small cell lung cancer

Lung cancer represents the leading cause of cancer mortality worldwide. Despite improvements in preoperative staging, surgical techniques, neoadjuvant/adjuvant options and postoperative care, there are still major difficulties in significantly improving survival, especially in locally advanced non-small cell lung cancer (NSCLC). To date, surgical resection is the primary mode of treatment for stage I and II NSCLC and has become an important component of the multimodality therapy of even more advanced disease with a curative intention. In fact, in NSCLC patients with solitary distant metastases, surgical interventions have been discussed in the last years. Accordingly, this review displays the recent surgical strategies implemented in the therapy of NSCLC patients.     

Radical treatment of non-small cell lung cancer during the last 5 years

The management of non-small cell lung cancer (NSCLC) has continued to improve over the last 5 years due to advances in surgery, radiological staging, combined modality therapies and advances in radiation technology.We have an updated staging classification (7th Edition American Joint Committee on Cancer staging) and now in 2011, a new histology classification introducing the concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma. This classification has profound surgical implications as the role of limited resection is reconsidered for early stage lesions. Surgery is curative in early stage disease. The role of surgery in locally advanced NSCLC remains controversial. The principal aim is a complete resection as this will determine long-term prognosis. Intraoperative staging of lung cancer is extremely important to determine the extent of resection according to the tumour and nodal status. Systematic nodal dissection is generally advocated to obtain accurate intraoperative staging and to help decide on adjuvant therapy.Radiotherapy currently plays a major role in the management of lung cancer as most patients are not surgical candidates due to disease stage, fitness and co-morbidities. In the last 5 years we have seen continuing optimisation of chemo-radiotherapy combinations and technological advances including the development of image guided radiotherapy (IGRT), stereotactic ablative body radiotherapy (SABR) and intensity modulated radiotherapy (IMRT).Quality of life evaluation is becoming increasingly important and should be considered when deciding on a specific treatment, especially in a multimodality setting.     

Current standards and ongoing controversies in the management of locally advanced non-small cell lung cancer

Despite the fact that nearly half of all patients with non-small cell lung cancer (NSCLC) present with stage III disease, this is the treatment setting with the least well-established standards. Generally treated with curative intent, patients with stage III disease usually receive more than one of the three main therapeutic approaches to lung cancer-surgery, radiation, and chemotherapy. In addition, the staging system encompasses a remarkably heterogeneous range of tumor burden and location within the rubric of stage III. Consequently, an individualized approach is often invoked to address particular concerns for resectability, toxicity, and patient and physician preferences. For patients with locally advanced NSCLC, therapeutic outcomes have improved overall for this population over the past few decades. While there exists a range of acceptable standard approaches to the treatment of stage III NSCLC, this review will describe several conclusions that have emerged and how they evolved.     

Photodynamic therapy, Nd-YAG laser and electrocautery for treating early-stage intraluminal cancer: which to choose?

The degree of healing and damage of the bronchial wall after photodynamic therapy, Nd-YAG laser and electrocautery for intraluminal early-stage cancer have been analysed. Review of the bronchoscopy reports and follow-up histology specimens of twenty-nine patients treated bronchoscopically with curative intent for their intraluminal tumor have been performed. Seventeen patients had been treated with bronchoscopic electrocautery (BE) only, six with photodynamic therapy (PDT) and six with Nd-YAG laser. Bronchial wall scarring seen during follow-up bronchoscopy was scored and subepithelial fibrosis were histologically evaluated using Alcian blue staining, Azan staining and polarised light. After BE, prominent airway scarring was seen in five patients (29%), with significant stenosis (>50% lumen) in one of these cases. Prominent scarring and significant stenosis were found in four (67%), after PDT. In five (83%) after Nd-YAG laser prominent scarring was found, one patient had significant stenosis. In three cases, two after BE and one after PDT, subepithelial tissue in the follow-up biopsies was insufficient for proper histologic examination. In the remaining biopsy specimen only one (7%) showed a moderate or excessive amount of fibroblasts after BE, whereas for PDT and Nd-YAG this was found in three (60%) and four patients (67%), respectively. Excessive matrix was found in none of the biopsies after BE, in two (40%) after PDT and in three (50%) after Nd-YAG laser. Compact collagen formations were seen in two (12%) biopsies after BE, in two (40 and 33%) after PDT and Nd-YAG, respectively. Compared to electrocautery, more airway scarring and more subepithelial fibrosis were seen after treatment with PDT and Nd-YAG laser. These findings, especially regarding PDT, is in contrast to the assumption that PDT is selective and may be important in the choice of treatment for patients with early stage cancer.     

Seeking improved outcome in the curative treatment of non-small-cell lung cancer

Progress is being made in the treatment of patients with early (stage I-III) and unresectable locally advanced (stage III) non-small-cell lung cancer (NSCLC). The primary modality of treatment is complete surgical resection of the malignant growths. However, not all patients are appropriate candidates for surgery, and the majority who undergo surgical resection have a poor survival. Recurrence and death are most commonly due to systemic failure, indicating micrometastatic disease. Treatments targeted at eradicating micrometastatic disease, such as adjuvant therapy, induction chemotherapy, concurrent chemoradiotherapy, and intensified radiotherapy, are currently being explored as a means to improve outcome in the curative treatment of NSCLC.     

What is early lung cancer? A review of the literature

The dismal cure rate of patients with lung cancer and the stage shift hypothesis have propelled the interest to perform screening at large, despite that previous randomized clinical trials failed to show any mortality benefit and the controversial issue of overdiagnosis. Due to early detection programs, a larger number of individuals at risk will be found to harbor small and potentially malignant early stage lesions. The application of non- and minimal invasive techniques for early detection, staging and treatment will become increasingly important. This review deals with the available clinical, surgical and pathological data focusing on early lung cancer lesions < or =1 cm. Literature data from both centrally located and parenchymal lesions < or =3 cm. have been analyzed. For all sub-centimeter lesions, minimal invasive staging and treatment approaches must still be considered inappropriate. Less invasive and less extensive treatment methods may be considered in high risk individuals with < or =1 cm. peripheral lesion showing > or =50 ground glass opacity on high resolution CT scan and those with superficial lesion in their central airways without deeper tumor invasion in the bronchial wall. Caution is necessary, however, as clinical staging remains inferior to pathological staging which is based on tissue samples collected after complete tumor removal and mediastinal lymph nodes dissection have been performed.     

Current surgical treatment of non-small-cell lung cancer

When considering surgical treatment for non-small-cell lung cancer (NSCLC), a distinction is made between early-stage disease (stages IA/B and IIA/B), locoregionally advanced disease (stages IIIA/B) and metastatic disease (stage IV). Complete surgical resection of NSCLC can provide good long-term outcome. Surgery is considered the treatment of choice in patients with early-stage NSCLC or patients with T3N1 disease. Surgery for locoregionally advanced disease remains controversial. In specific cases of T4 disease, surgery can provide long-term survival. In patients with stage IIIA-N2 disease, surgery is only offered to patients who have achieved mediastinal downstaging following induction therapy. Careful preoperative evaluation is clearly important in the staging and selection of patients with NSCLC for surgery.     

Considerations for the Surgical Management of Early Stage Lung Cancer During the COVID-19 Pandemic

The highly transmissible novel coronavirus (COVID-19) has infected over 8.8 million people globally and has upended the delivery of health care in the United States, creating unprecedented challenges to providing care to patients with early stage non–small cell lung cancer (NSCLC). The initial surge of patients with COVID-19 that have flooded hospitals has put a strain on physical space, workforce, and supplies. In addition, social distancing and the risk of COVID-19 transmission has created significant barriers for thoracic surgeons to diagnose and treat patients. Many hospitals across the country have temporarily suspended elective operations to preserve hospital beds, ventilators, and personal protective equipment. Currently, the pandemic has greatly disrupted the current standard of resection after adequate staging with imaging and/or surgical staging for early stage NSCLC well beyond the initial acute phase; therefore, a new paradigm for effective management will need to be devised until the COVID-19 pandemic is eradicated with systematic vaccination and herd immunity. Thoracic surgeons will need to recalibrate their approach to ensure that patients receive timely and effective treatment for early stage NSCLC. The management of early stage NSCLC during the COVID-19 pandemic should be balanced with available hospital resources, risk of progression of disease, risk of transmission of COVID-19 to patient and surgeon, and the availability of alternative therapies. This article will address the current challenges with treating early stage NSCLC during the COVID-19 pandemic and provide a clinical framework for providing effective surgical therapy while mitigating the risk of transmission of the SARS-CoV-2 virus to patients and surgeons.     

PET/CT纵隔淋巴结SUVmax与N0~N 1期非小细胞肺癌手术患者预后相关性的研究

  目的  评价NSCLC患者行根治性切除术后, 纵隔淋巴结组织学检查阴性(N0~N1期)的患者术前纵隔淋巴结FDG摄取水平对患者预后的意义。  方法  回顾性总结了2005年4月至2009年5月在天津医科大学附属肿瘤医院行PET/CT检查后接受手术治疗的N0~N1期NSCLC患者的PET/CT数据、术后随访资料及临床资料。运用Kaplan-Meier法及Log-rank检验对纵隔淋巴结SUV_max以及性别、年龄、组织学类型、TNM分期、术后辅助治疗、原发病灶SUV_max等分别与患者生存时间进行单因素生存分析, 采用Cox回归风险比例模型对影响预后的各因素进行多因素生存分析。  结果  单因素分析表明, 术前PET/CT纵隔淋巴结SUV_max(P=0.001)以及TNM分期(P < 0.001)、原发病灶SUV_max(P=0.001)、是否有术后辅助治疗(P=0.012)对N0~N1期NSCLC患者术后预后存在预测作用; 多因素分析表明, 只有TNM分期(P=0.017)、原发病灶SUV_max(P=0.027)及纵隔淋巴结SUV_max(P=0.046)是影响本组NSCLC患者术后生存的独立预后因素, 三者的相对危险度分别为2.230, 2.179及1.962。  结论  对于N0~N1期的NSCLC术后患者, 术前PET/CT纵隔淋巴结SUV_max、TNM分期、原发病灶SUV_max均是影响患者术后生存的因素。将三者结合起来, 对于指导临床尽早制定术后个体化治疗方案、延长患者生存期具有重要意义。      

Adjuvant treatment of non-small-cell lung cancer: how do we improve the cure rates further?

Surgery remains the initial treatment for patients with early-stage non-small-cell lung cancer (NSCLC). Additional therapy is necessary because of high rates of distant and local disease recurrence after surgical resection. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. Since then, a new generation of randomized phase III trials have been conducted, some of which have reported a benefit for chemotherapy in the adjuvant setting. The role of postoperative radiation therapy remains to be defined. It may not be beneficial in early-stage NSCLC but still may have utility in stage IIIA disease. Improvement in survival outcomes from adjuvant treatment are likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Preliminary results with gene-expression profiles and lung cancer proteomics have been promising. These techniques may be used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. All of these innovations will hopefully increase cure rates for lung cancer patients by maximizing the efficacy of adjuvant therapy.     

Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography.

Tumor proliferation has prognostic value in resected early-stage non-small cell lung cancer (NSCLC). We evaluated whether [F-18]fluorodeoxyglucose (FDG) uptake of NSCLC correlates with tumor proliferation and, thus, could noninvasively grade NSCLCs (refining patient prognosis and therapy). Thirty-nine patients with potentially resectable NSCLC underwent whole-body FDG positron emission tomography (PET) 45 min after i.v. injection of 10 mCi of FDG. Tumor FDG uptake was quantitated with the maximum pixel standardized uptake value (maxSUV). The lesion diameter from computed tomography was used to correct the maxSUV for partial volume effects using recovery coefficients determined for the General Electric Advance PET scanner. Thirty-eight patients underwent complete surgical staging (bronchoscopy and mediastinoscopy, with or without thoracotomy). One stage IV patient by PET underwent bronchoscopic biopsy only. Immunohistochemistry for Ki-67 (proliferation index marker) was performed on all of the 39 NSCLC specimens (35 resections, 1 percutaneous, and 3 surgical biopsies). The specimens were reviewed for cellular differentiation (poor, moderate, well) and tumor type. Lesions ranged from 0.7 to 6.1 cm. The correlation found between uncorrected maxSUV and lesion size (Rho, 0.56; P = 0.0006) disappeared when applying the recovery coefficients (Rho, -0.035; P = 0.83). Ki-67 expression (percentage of positive cells) correlated strongly with FDG uptake (corrected maxSUV: Rho, 0.73; P < 0.0001). The correlation was stronger for stage I lesions (11 stage IA, 15 stage IB): Rho, 0.79; P < 0.0001) and strongest in stage IB (Rho, 0.83; P = 0.0019). A significant association (P < 0.0001) between tumor differentiation and corrected SUV was noted. FDG PET may be used to noninvasively assess NSCLC proliferation in vivo, identifying rapidly growing NSCLCs with poor prognosis that could benefit from preoperative chemotherapy.     

Basic treatment considerations: chemotherapy

Lung cancer represents a major global health problem, with more than a million deaths reported each year. Because there are no effective screening tools to date, diagnosis of the disease at an advanced stage is a common feature. Over the past 20 years, elegant strides have been made in the treatment of patients with advanced NSCLC. Several novel chemotherapy agents that are efficacious and possess favorable toxicity profiles have been developed recently. In addition to evaluating novel combinations, alternative schedules to improve toxicity profiles are subjects of clinical trials. Much work needs to be done, however, to improve the outcome for patients with lung cancer. Chemotherapy extends life and improves quality of life for patients with stage IIIB/IV NSCLC. Combined modality therapy with radiation and chemotherapy improves the outcome for patients with locally advanced NSCLC and is associated with a curative potential. Molecularly targeted therapies are under rigorous evaluation, although the initial results have been disappointing. In the upcoming years, we will learn effective means to incorporate molecularly targeted therapies to existing treatment paradigms in lung cancer.     

Platinum-Based Chemotherapy in Lung Cancer Affects the Expression of Certain Biomarkers Including ERCC1

Chemotherapies are widely used in the treatment of lung cancer. However, little is known about their effect in the expression of different tissue markers. Seventeen lung cancer tissue blocks obtained by bronchoscopic biopsies together with their corresponding surgical biopsies after neoadjuvant chemotherapy were studied. They included 9 adenocarcinomas (ADC) and 8 squamous cell carcinomas (SCC). Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues to study the expression of Ki-67, p53, Bcl-2, Bax, Fas-ligand and ERCC1 (excision repair cross-complementation group 1). Out of 17 NSCLC 6 expressed proapoptotic markers and 4 expressed antiapoptotic markers, while in 7 cases the apoptotic markers did not show detectable changes after neoadjuvant chemotherapy. Six of 17 bronchoscopic NSCLC cases expressed increased level of Ki-67 after neoadjuvant treatment. Eight bronchoscopic NSCLC tissues (6 SCC, 2 ADC) expressed ERCC1. All but one ADC became ERCC1 negative after neoadjuvant therapy. There was no newly expressed ERCC1 positive case in the surgical biopsy group. Platinum-based neoadjuvant chemotherapy had no effect on the apoptotic activity of 17 patients’ tumor specimen, however, 6 of 17 bronchoscopic NSCLC cases expressed increased level of Ki-67 after neoadjuvant treatment, in 3 cases the level of Ki-67 became decreased, while 8 cases had no detectable change of proliferation activity. The results of the present study suggest that platinum-based chemotherapy probably induces a selection of tumor cells with more aggressive phenotype, and also affects the expression of tissue marker (ERCC1) that could have predictive value.     

免疫微环境与非小细胞肺癌预后关系的研究进展

肺癌是发病率和死亡率增长最快的恶性肿瘤,其中非小细胞肺癌(NSCLC)约占85％.肺癌的治疗已从最初的手术切除、外科辅助治疗、放化疗、靶向治疗,发展到目前比较热门的免疫治疗,但仍只有少数患者能够从中受益.大量研究发现肿瘤微环境不仅影响肿瘤的发生发展,而且与肿瘤的复发及临床结果密切相关.现主要围绕免疫细胞、免疫结构,探讨免疫微环境作为NSCLC预后标志物的研究进展.     

Concurrent docetaxel and thoracic radiation in non-small-cell lung cancer

Locally advanced (stages IIIA and IIIB) non-small-cell lung cancer (NSCLC) represents approximately 25% of new cases of NSCLC diagnosed annually. The treatment strategy for these patients involves combined-modality therapy with chemotherapy and thoracic radiation. Furthermore, a subset of patients with stage IIIA disease undergo surgical resection. Docetaxel is a chemotherapy agent with activity in both first- and second-line treatment of patients with advanced NSCLC. Several recent studies have also incorporated docetaxel in the treatment of patients with stage III NSCLC as neoadjuvant therapy, alone or in combination with cisplatin or carboplatin and thoracic radiation. Docetaxel has also been used as consolidation therapy. This review will summarize the data to date on the use of docetaxel and thoracic radiation in the treatment of patients with stage III NSCLC.     

Clinical impact of (18)F fluorodeoxyglucose positron emission tomography in patients with non-small-cell lung cancer: a prospective study.

PURPOSE: To prospectively study the impact of (18)F fluorodeoxyglucose (FDG) positron emission tomography (PET) on clinical management of patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred five consecutive patients with NSCLC undergoing (18)F FDG PET were analyzed. Before PET, referring physicians recorded scan indication, conventional clinical stage, and proposed treatment plan. PET scan results were reported in conjunction with available clinical and imaging data, including results of computed tomography (CT). Subsequent management and appropriateness of PET-induced changes were assessed by follow-up for at least 6 months or until the patient's death. RESULTS: Indications for PET were primary staging (n = 59), restaging (n = 34), and suspected malignancy subsequently proven to be NSCLC (n = 12). In 27 (26%) of 105 of cases, PET results led to a change from curative to palliative therapy by upstaging disease extent. Validity of the PET result was established in all but one case. PET appropriately downstaged 10 of 16 patients initially planned for palliative therapy, allowing either potentially curative treatment (four patients) or no treatment (six patients). PET influenced the radiation delivery in 22 (65%) of 34 patients who subsequently received radical radiotherapy. Twelve patients considered probably inoperable on conventional imaging studies were downstaged by PET and underwent potentially curative surgery. PET missed only one primary tumor (5-mm scar carcinoma). CT and PET understaged three of 20 surgical patients (two with N1 lesions < 5 mm and one with unrecognized atrial involvement), and PET missed one small intrapulmonary metastasis apparent on CT. No pathological N2 disease was missed on PET. CONCLUSION: FDG PET scanning changed or influenced management decisions in 70 patients (67%) with NSCLC. Patients were frequently spared unnecessary treatment, and management was more appropriately targeted.