Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combination of carboplatin and paclitaxel is an active regimen in non-small cell lung cancer (NSCLC). Historically, patients with stage III disease have manifested higher response rates than patients with metastatic disease, and patients achieving a pathologic complete response to induction chemoradiation therapy prior to surgery have shown better long-term outcome. Based upon our pilot data using high-dose carboplatin and paclitaxel, we designed a phase II trial in patients with marginally resectable stage IIIA NSCLC. Ten patients, with bulky nodal stage IIIA disease, initially received etoposide (2 g/m2) and granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC). Two cycles, 28 days apart, of carboplatin (AUC 12 in seven patients; AUC 16 in three patients) and paclitaxel (250 mg/m2) were administered with filgrastim (5 microg/kg) and PBSC support. After re-evaluation, patients underwent a thoracotomy followed by radiotherapy (44-60 Gy) if deemed resectable, or radiotherapy alone (60 Gy) if not resectable. The median age was 58.5 years (48-66) with a median ECOG performance status of 0 (0-1). Histology was adenocarcinoma in seven patients; the remainder had either squamous cell, large cell or bronchoalveolar carcinoma. Based on CT radiography, the overall response rate was 40%. Eight of ten patients underwent resection with four right pneumonectomies, three right upper lobectomies and one wedge resection of the right upper lobe. Six patients had a complete resection. Of eight patients resected, four were downstaged by induction therapy, three remained unchanged and one was found to have more extensive disease. The remaining two patients developed metastatic disease while receiving chemotherapy. The median dose of postoperative radiotherapy was 54 Gy (35-66 Gy). Actual median follow-up for all patients was 89 weeks (25 to 136+). The actuarial median overall survival was 124 weeks (25 to 136+) and time to progression was 57 weeks (17 to 136+). The median dose of carboplatin delivered expressed as mg/m2 was 779 (615-1540). Neutropenic fever occurred in two patients during the initial mobilization cycle only. The median number of units of RBC and/or platelets transfused was 0 (0-2 and 0-6, respectively). There were no significant non-hematologic toxicities. High-dose induction chemotherapy with stem cell rescue is feasible and safe with an acceptable response rate. Thoracotomy, including pneumonectomy and postoperative radiotherapy, were well tolerated by patients after undergoing high-dose induction chemotherapy with no apparent increase in peri-operative morbidity. The pathologic complete response rate was low--one out of ten patients. These results indicate that dose escalation of induction chemotherapy does not improve response rates even in this highly selected patient population. Accordingly, the complexity and potential toxicity of high-dose chemotherapy, as delivered in this trial as neoadjuvant treatment of non-small cell lung cancer, is not warranted.
Lung Cancer 2000 Jan
PMID:Phase II trial of induction high-dose chemotherapy followed by surgical resection and radiation therapy for patients with marginally resectable non-small cell carcinoma of the lung. 1067 82

There are few reports of a surgical approach to T4 lung carcinoma that has invaded the heart. Although most cases will be considered inoperable, cases in which there is potential for complete resection and no distant or nodal metastatic disease (T4 N0 M0, Stage IIIB) may be considered for surgical therapy. We report a case of squamous cell carcinoma of the lung with cardiac involvement, in which we performed a completion pneumonectomy using total cardiopulmonary bypass. We describe indications and techniques for use of cardiopulmonary bypass in such cases.
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PMID:Atrial resection in advanced lung carcinoma under total cardiopulmonary bypass. 1092 96

DNA mismatch repair genes have been implicated in the pathogenesis and predisposition of certain malignancies through a mutator phenotype. In this study, we investigated, in 150 non-small cell lung carcinomas, the expression levels of hMLH1 and hMSH2 proteins in relation to loss of heterozygosity on chromosomes 3p and 2p, the mutational status of these genes' promoters and the hot spot exons. We have demonstrated that 88 of 150 (58.6%) tumor specimens had reduced expression levels of the hMLH1 protein, whereas 85 of 147 (57.8%) specimens had reduced expression levels of the hMSH2 protein. Reduced expression levels of both proteins were observed in 51 of 150 (34%) specimens. In adenocarcinomas, the reduction of hMSH2 expression was more frequently observed than that of hMLH1 (P<0.003), whereas in squamous cell carcinoma of the lung hMLH1 expression was more frequently reduced than hMSH2 (P<0.006). Reduced expression of hMLH1correlated with allelic imbalance on loci D3S1289 (P<0.0002) and D2S391 (P<0.05). It is of note that an inverse correlation was found between hMSH2 reduced expression and loss of heterozygosity at locus D3S1300 (P = 0.016). In addition, hMLH1 reduced expression was more frequently associated with heavy smokers, assessed by daily tobacco uptake (P = 0.018) and total smoking exposure (pack-years; P<0.05). In addition, a correlation between hMLH1 reduced expression and nodal metastasis in squamous cell carcinoma of the lung was observed (P = 0.015). No mutations were identified in the promoters or exons examined in these two genes. These findings indicate that hMLH1 and hMSH2 gene inactivation is a common event in the development of non-small cell lung carcinoma and allelic loss seems to be a major genetic event involved in hMLH1 silencing. In addition, we propose that a putative negative regulator of hMSH2 gene may be located at the locus 3p14.
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PMID:hMLH1 and hMSH2 expression correlates with allelic imbalance on chromosome 3p in non-small cell lung carcinomas. 1094 33

The clinical improvement obtained with combination treatment has modified the therapeutic approach of lung cancer in HIV-positive patients. Aggressive surgical treatment has become a viable option for those patients in whom the CD4(+) cell count was greater than 200 lymphocytes/mm(3). We recently extended our surgical indications to include two HIV-positive patients with lung cancer (stage IIIA and IIB) and low (<200 lymphocytes/mm(3)) CD4(+) count. Both patients underwent a lobectomy and mediastinal nodal dissection. The postoperative course was uneventful. No evidence of recurrent cancer was seen at 12 and 20 months after the operation. Based on this limited experience, we conclude that a low CD4(+) count should not represent, per se, an exclusion criterion for the surgical treatment of pleuropulmonary conditions in HIV-positive patients.
Lung Cancer 2000 Aug
PMID:Pulmonary resection for lung cancer in HIV-positive patients with low (<200 lymphocytes/mm(3)) CD4(+) count. 1096 45

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine dermal neoplasm. Because of the limited number of cases described in the literature (approximately 600 to date), statistically significant data regarding treatment are difficult to obtain. The majority of MCC cases affect the head and neck and are thought to be caused by the actinic damage associated with sun exposure. This study evaluates cases of head and neck MCC at Naval Medical Center San Diego (NMCSD) and compares the treatment regimens and outcomes from multiple institutions. This study is a retrospective outcomes analysis of all cases of head and neck MCC seen at NMCSD, between January 1, 1988 and June 30, 1998. The records of the NMCSD Tumor Registry were searched for patients with that diagnosis, and supplemental information was retrieved from the Radiation Oncology and Head & Neck Surgery Clinic charts. Eight of nine patients in this study were treated with either wide-local excision or Mohs microsurgery. The surgical margins were free of disease in all eight patients. One patient presented with distant metastatic disease, and two others were subsequently found to have nodal involvement. Subsequent therapy varied among the patients. Survey of the available literature revealed inconsistency in terms of which treatment regimens are optimal. Tumor resections are recommended by most groups to include a 2-cm to 3-cm tumor-free margin around the primary lesion when possible, but this is often difficult to achieve in the head and neck. Data, which do not reach statistical significance, suggest improved outcomes with tumor-free margins. Treatment of the regional draining lymph nodes is also recommended in most series. Prophylactic lymph node dissection or radiation therapy to the nodal chain may decrease local recurrence but does not consistently affect overall survival. Adjuvant chemotherapy is advocated by most groups in the treatment of metastatic disease because MCC is pathologically similar to small-cell lung carcinoma. However, no chemotherapy protocol has been shown to improve survival. Head and neck MCC is a rare and aggressive dermal tumor of neuroendocrine origin that requires multimodality therapy, including surgery, radiation therapy, and possibly adjuvant chemotherapy. Multiinstitutional studies are crucial to obtain sufficiently large populations to investigate and optimize therapy in this disease.
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PMID:Merkel cell carcinoma arising in the head and neck: optimizing therapy. 1123 47

A sixty-one-year-old man was admitted to our hospital because of a right lung tumor shadow. He had been diagnosed as having sarcoidosis at the age of fifty-seven. He was newly diagnosed as having squamous cell carcinoma by trans bronchial biopsy. He was treated with an induction chemotherapy (cisplatin 80 mg/m2 + vinorelbine 20 mg/m2) followed by right middle and lower lobectomy with a mediastinal nodal dissection, because the stage of his carcinoma was cT2N2M0. Resected lung tissue showed the disappearance of cancer cells. Dissected mediastinal and hilar lymph nodes showed many sarcoid granulomas. Cisplatin combined with vinorelbine might be an effective chemotherapy for non-small cell lung carcinoma.
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PMID:[Induction chemotherapy (cisplatin + vinorelbine) is found to be markedly effective for squamous cell lung carcinoma with sarcoidosis--a case report]. 1124 53

No therapy is currently available for patients with recurrent vascular obstruction of the superior vena cava (SVC) caused by tumor regrowth after chemotherapy or radiation therapy. Intravascular stenting is a new option for the treatment of vena cava syndrome. Forty cancer patients with SVC syndrome (SVCS) were evaluated by computed tomography (CT) and venography. The SVC or its tributaries were stenosed or thrombosed in all patients. The etiology was malignant in all but 2 cases: non-small-cell lung carcinoma (n = 28), mediastinal nodal metastasis (n = 5), lymphoma (n = 2), pleural mesothelioma (n = 2), small-cell lung carcinoma (n = 1), and postradiation fibrous mediastinitis (n = 2). Stenting was achieved in 39 of the 40 patients, and clinical symptoms subsided in 92%. Stents remained patent in 36 of these 39 patients throughout a mean follow-up of 24 weeks (range 3 days to 24 months). SVC stenting is safe, effective and allows rapid cure of SVCS and port catheter implantation in patients in poor health.
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PMID:Superior vena cava obstruction: is stenting necessary? 1130 67

New trends in lung cancer surgery focus on new approaches to the management of the primary tumour, combined modality approaches to both local and distant control of the tumour, new approaches to ensure resectability by staging and techniques to expand the limits of operability. With new screening methods for NSCLC there is a trend toward sublobar, segmental resections of smaller tumours including an expanding use of video assisted thoracoscopy. Improvements in surgical and anaesthetic procedures have stimulated a renewed interest in the resection of locally advanced tumours. The understanding that local control alone may not give the best chance of long term survival has stimulated new trends in the use of neoadjuvant and adjuvant chemotherapy. There is a trend towards more detailed preoperative and intraoperative nodal staging in NSCLC, including video assisted techniques, and the identification of sentinel lymph node involvement to direct lymph node dissection. Increased understanding of the physiological benefits of surgery in emphysema have resulted in a re-evaluation of the selection of patients for lung cancer surgery. This together with a greater application of bronchoplastic and angioplastic techniques is leading to greater resection rates.
Lung Cancer 2001 Dec
PMID:Surgery for non-small cell lung cancer--new trends. 1172 Jul 54

There is a resurgence of interest in lung cancer screening, motivated by the fact that many lung cancer patients cannot be cured due to advanced disease at presentation. Lung cancer screening may detect more early stage disease. Very early stage squamous cell type lung cancer in the central tracheobronchial tree can be detected and local bronchoscopic treatments such as photodynamic therapy can be applied if the tumor is strictly intraluminal and nodal disease is absent. So, accurate staging regarding tumor size and nodal disease is much more important than treatment per se. Bronchoscopic treatments are less morbid treatment alternatives than surgery and surgical bronchoplasty, especially for patients suffering from COPD and who have poor cardiovascular status due to their smoking history.
Lung Cancer 2001 Dec
PMID:The role of photodynamic therapy in the management of stage I/II NSCLC. 1174 Sep 91

This study was performed to investigate the utility of FDG-PET for: (1) initial staging, and (2) restaging of the primary and mediastinal nodal lesions 2 weeks after the completion of preoperative chemoradiotherapy in patients with stage III non-small cell lung cancer (NSCLC). Twenty-six patients with histologically confirmed stage III NSCLC were accrued to this study from April 1993 to July 1998. They included 21 with stage IIIA (N2) NSCLC who were enrolled into an institutional phase II study, and 5 patients with a highly selected subset of stage IIIB disease characterized by the presence of microscopic metastatic disease in contralateral mediastinal lymph nodes who were also treated with preoperative chemoradiotherapy; N3 lesions (n=3) and minimal T4 lesions. Demographic characteristics included median age 62 years (a range from 47 to 73) and gender ratio of male 15 to female 11. Histologic types of tumor consisted of squamous cell carcinoma 6, adenocarcinoma 11, large cell carcinoma 5, and non-small cell carcinoma 4. All patients had FDG-PET imaging of the chest before the initiation and 2 weeks after completion of preoperative therapy. The FDG-PET images were evaluated qualitatively for uptake at the primary tumor sites and mediastinal lymph nodes. Standard uptake values (SUVs) were also calculated for the primary tumors and all PET findings were correlated with surgical histopathologic data. Preoperative chemoradiotherapy resulted in complete pathologic response in 8 of 26 primary lesions. By qualitative analysis, 96% of these tumors showed level 3 or 4 uptake before preoperative chemoradiotherapy. After chemoradiotherapy, 57% (15/26) of patients showed at least a one level decrease in uptake, and the sensitivity and specificity of FDG-PET for differentiating residual tumor from pathologic complete response were 67% (12/18) and 63% (5/8). Mean SUV was 14.87+/-7.11 at baseline and decreased to 5.72+/-3.35 after chemoradiotherapy (n=21, P<0.00001). When a value of 3.0 was used as the SUV cut-off, sensitivity and specificity were 88 and 67%, respectively. The mean values of visual intensity were 3.87+/-0.35 and 3.8+/-0.51 for patients who achieved pathologic complete response (n=8) and for those who showed residual cancer after the preoperative therapy (n=18), respectively. The mean SUVs were 16.97+/-8.52 and 14.03+/-6.61 for patients who achieved pathologic complete response (n=6) and for those who showed residual cancer (n=15) after the preoperative therapy, respectively. Therefore, the degree of FDG uptake before preoperative chemoradiotherapy did not provide predictive value for subsequent tumor response. For mediastinal initial staging, the sensitivity and specificity of FDG-PET were 75 and 90.5%. The sensitivity and specificity of FDG-PET for mediastinal restaging were 58.0 and 93.0%. These results indicate that FDG-PET is useful for monitoring the therapeutic effect of neoadjuvant chemoradiotherapy in patients with stage III NSCLC. For the primary lesions, SUV based analysis has high sensitivity but limited specificity for detecting residual tumor. In contrast, for restaging of mediastinal lymph nodes, FDG-PET is highly specific, but has limited sensitivity.
Lung Cancer 2002 Feb
PMID:FDG-PET in staging and restaging non-small cell lung cancer after neoadjuvant chemoradiotherapy: correlation with histopathology. 1180 91


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