Adrenalectomy for solitary adrenal metastasis from colorectal carcinoma

A 60-year-old man underwent anterior resection for advanced rectal carcinoma. Seven years and 2 months later, right lower pneumonectomy was performed for a metastatic lung tumor. Two years and 2 months thereafter, left adrenalectomy was performed for solitary adrenal metastasis. The patient remained disease-free for 10 months postoperatively, until multiple lung metastases appeared. The patient is alive and well, under mild chemotherapy with oral doxifluridine, 3 years and 5 months after left adrenalectomy. We conclude that patients with solitary adrenal metastasis may benefit from surgical resection and that resection could be considered as a therapy for solitary adrenal metastasis from colorectal carcinoma.     

Adjuvant therapy for resected non-small cell lung cancer

Surgery remains the initial treatment for patients with early-stage non-small cell lung cancer (NSCLC). The frequent occurrence of distant metastases and local regional failure after surgical resection would indicate that additional treatment is necessary. 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. This was followed by a new generation of randomized phase III trials some of which have reported a benefit for chemotherapy in the adjuvant setting. Based on the results of these trials, platin-based chemotherapy has become the standard of care for resected stages II and IIIA NSCLC. The role of postoperative radiation therapy remains to be defined. In the future, improvement in survival outcomes from adjuvant treatment is 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. Gene expression profiles and proteomics are techniques being used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. Increasing the understanding of the molecular makeup of lung cancer will hopefully increase cure rates for patients by maximizing the efficacy of the adjuvant therapy.     

Treatment options for brain metastases in patients with non-small cell lung cancer

Opinion statement Brain metastases are a common complication for patients with non-small cell lung cancer and a significant cause of morbidity and mortality. In the past, treatment of brain metastases and lung cancer focused on symptom palliation with whole brain radiotherapy (WBRT) and steroids because of the grim outlook for patients. However, recent advances in technology and surgical techniques have created more options for the management of brain metastases, which include surgery, irradiation, stereotactic radiosurgery, and chemotherapy. These aggressive approaches have resulted in an improvement of neurologic outcomes and survival rates of patients with non-small cell lung cancer. Central nervous system (CNS) metastases can be divided into three groups: solitary CNS metastases with controlled or controllable primary disease, oligometastatic disease (fewer than three metastases), and multiple metastases. For patients with solitary CNS metastases, long-term survival is possible. A radical treatment approach involving surgical resection or radiosurgery, followed by WBRT, is recommended. For patients with oligometastatic disease, surgical resection or radiosurgery is considered in selected cases and WBRT is indicated. For patients with multiple metastases, WBRT is recommended. For patients with oligometastatic disease and patients with multiple metastases, recent evidence indicates that systemically effective chemotherapy may produce responses and can be instituted safely before radiotherapy. The treatment timing of chemotherapy and radiotherapy should be individualized.     

Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis

BACKGROUND: Solitary brain metastases occur in about 50% of patients with brain metastases from nonsmall cell lung cancer (NSCLC). The standard of care is surgical resection of solitary brain metastases, or stereotactic radiosurgery (SRS) plus whole brain radiation therapy (WBRT). However, the optimal treatment for the primary site of newly diagnosed NSCLC with a solitary brain metastasis is not well defined. The goal was to distinguish which patients might benefit from aggressive treatment of their lung primary in patients whose solitary brain metastasis was treated with surgery or SRS. METHODS: The cases of 84 newly diagnosed NSCLC patients presenting with a solitary brain metastasis and treated from December 1993 through June 2004 were retrospectively reviewed at The University of Texas M. D. Anderson Cancer Center. All patients had undergone either craniotomy (n = 53) or SRS (n = 31) for management of the solitary brain metastasis. Forty-four patients received treatment of their primary lung cancer using thoracic radiation therapy (median dose 45 Gy; n = 8), chemotherapy (n = 23), or both (n = 13). RESULTS: The median Karnofsky performance status score was 80 (range, 60-100). Excluding the presence of the brain metastasis, 12 patients had AJCC Stage I primary cancer, 27 had Stage II disease, and 45 had Stage III disease. The median follow-up was 9.7 months (range, 1-86 months). The 1-, 2-, 3-, and 5-year overall survival rates from time of lung cancer diagnosis were 49.8%, 16.3%, 12.7%, and 7.6%, respectively. The median survival times for patients by thoracic stage (I, II, and III) were 25.6, 9.5, and 9.9 months, respectively (P = .006). CONCLUSIONS: By applying American Joint Committee on Cancer staging to only the primary site, the thoracic Stage I patients in our study with solitary brain metastases had a more favorable outcome than would be expected and was comparable to Stage I NSCLC without brain metastases. Aggressive treatment to the lung may be justified for newly diagnosed thoracic Stage I NSCLC patients with a solitary brain metastasis, but not for locally advanced NSCLC patients with a solitary brain metastasis.     

Adjuvant therapy of colon cancer: a review

Colon cancer is a common cause of cancer-related mortality. Complete surgical resection of the primary tumor and/or select metastatic lesions can be curative in many patients. The risk of recurrence after resection can be predicted by pathologic staging. Large prospective randomized trials over the past 2 decades have clearly shown an increased overall survival for patients with resected stage III colon cancer who are treated with adjuvant 5-fluorouracil-based chemotherapy. The benefit of adjuvant chemotherapy for patients with stage II disease remains controversial. There is indirect evidence to support adjuvant chemotherapy after resection of metastatic disease. Locoregional approaches such as radiation, hepatic arterial infusion, or portal vein chemotherapy remain investigational. Adjuvant immunotherapy with monoclonal antibodies is emerging as a therapeutic option that might complement chemotherapy. Future challenges include improving adjuvant chemotherapy with the addition and/or substitution of new agents, resolving which subset of patients with stage II and resected stage IV colon cancer might benefit from therapy, validating the benefit of immunotherapy, and investigating locoregional therapies compared with systemic therapy.     

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.     

Postsurgical adjuvant therapy in stages I, II, and IIIA non-small cell lung cancer

The prognostic importance of accurate staging of non-small cell lung cancer was established in 1974 and reaffirmed and refined in 1986. The concept of adjuvant therapy after pulmonary resection for lung cancer is justified by the behavior of the disease. The best available data pertinent to adjuvant therapy of lung cancer have been collected by The Lung Cancer Study Group over the past 13 years. These data are based on a commitment to prospective and standardized surgical staging as a basis for large-scale prospective randomized control trials. A treatment effect of combination chemotherapy has been detected for stage II and IIIA nonsquamous cancer and is suggested for squamous cancer as well. This treatment effect is of marginal clinical significance. Adjuvant therapy for stage I disease has not shown a detectable benefit. Adjuvant radiation therapy for stage II and IIIA squamous cell carcinoma likewise has not resulted in survival benefit. Systemic metastasis continues to be the major clinical problem in lung cancer treatment, and better systemic therapy is necessary to improve the outcome in this disease. However, some patients do benefit from adjuvant chemotherapy, and efforts to identify such patients prospectively are also the subject of current clinical research.     

Long-term survival after successful surgical treatment of a solitary brain metastasis

Background We investigated the factors associated with survival duration in 9 patients with brain metastases who survived for more than 6 years, and focused on the factors associated with long survival. Methods Of 9 primary lesions, 5 were lung cancer, 1 was colon cancer, 1 was uterine cancer, 1 was choriocarcinoma, and 1 was renal cancer. All patients underwent total removal of a solitary brain metastasis. Of the 9 patients, 6 received chemotherapy and adjuvant radiation therapy, 1 patient received only radiation therapy, and 2 patients had no adjuvant therapy. Results The factors we isolated in the 9 long-term survivors were that they were relatively young, their systemic diseases were well controlled, there was a relatively long interval between diagnosis of the primary tumor and the brain metastasis, the metastatic lesion was located in the nondominant hemisphere, and the patients were generally in good condition or had only a mild neurologic deficit. Conclusion In some patients with controlled or absent extracranial tumor activity in whom a single brain metastatic tumor is identified after a prolonged period, surgery and local radiotherapy may provide hope for a long survival period.     

Chemotherapy is the cornerstone of the combined surgical treatment of lung cancer with synchronous brain metastases

BACKGROUND: Lung cancer accounts for about 50% of brain metastases, of which nearly 25% are eligible for neurosurgery, providing a neurological control rate of up to 70% when followed by whole brain radiation therapy. How to manage the primary lung carcinoma remains elusive. METHODS: We undertook a retrospective study of consecutive patients who underwent surgical resection for synchronous brain metastases from non-small cell lung cancer in a single institution, to determine overall survival and prognostic factors, with particular attention to the treatment of the primary lung tumor. RESULTS: Fifty-one patients underwent surgical resection of synchronous brain metastases from non-small cell lung cancer. Median survival was 13.2 months. Prognosis mainly depended of the treatment of the lung tumor, with a marked survival advantage in the 29 patients receiving a focal treatment (thoracic surgery or radiotherapy), compared to the 22 other patients: median, 1-year, and 2-year survival were 22.5 months, 69%, and 42%, versus 7.1 months, 33%, and 5%, respectively (p<0.001); response to pre-operative chemotherapy before focal treatment was the main favorable prognostic factor (p=0.023), and further identified patients who had benefit from resection of the lung tumor, with a significantly better outcome. CONCLUSIONS: Chemotherapy, by its therapeutic and prognostic value, may be considered as the cornerstone of the combined medical and surgical therapeutic sequence whereby brain metastasectomy is followed by chemotherapy and further focal treatment of the primary lung tumor in responders to chemotherapy.     

宫颈癌肺转移患者手术治疗效果及预后因素分析

目的:通过对宫颈癌治疗后肺转移患者临床资料进行分析,评价外科手术治疗宫颈癌肺转移的疗效,研究影响患者生存的预后因素.方法:回顾性分析44例宫颈癌治疗后肺转移患者临床资料(手术组23例,对照组21例),采用Kaplan-Meier法进行生存分析,Log-rank检验进行单因素分析,COX风险回归模型进行多因素分析.结果:手术组1、2年生存率分别为78.2%、34.7%.手术组患者的生存曲线高于非手术组患者的生存曲线,差异有统计学意义(P<0.05),单因素分析显示,肿瘤分化程度、肺转移瘤数目、肺转移性肿瘤最大直径与患者生存率有关(P<0.05);COX比例风险回归模型分析显示,肺转移瘤数目及肺转移肿瘤最大直径是宫颈癌肺转移患者预后的独立影响因素(P<0.05).结论:对于肺转移灶数目较少,直径较小的患者,可从肺转移灶切除中获益,积极行肺转移瘤外科治疗有助于改善宫颈癌肺转移患者的长期预后.     

Annual Review of Advances in Lung Cancer Clinical Research: A Report for the Year 2009

The use of positron emission tomography compared with conventional staging increases the detection of extrathoracic metastases and reduces the number futile thoracotomies in patients being evaluated for surgical resection. Long-term follow-up of one of the two adjuvant chemotherapy trials revealed a continued overall survival (OS) benefit to adjuvant chemotherapy. In locally advanced non-small cell lung cancer, a phase III trial of chemoradiotherapy alone and with surgical resection revealed no statistically significant difference in OS between the treatment arms. In advanced stage non-small cell lung cancer, a phase III trial compared gefitinib with carboplatin and paclitaxel in a clinically enriched patient population for epidermal growth factor receptor (EGFR) tyrosine kinase (TK) mutations; among patients with an EGFR TK mutation, patients in gefitinib arm compared with carboplatin and paclitaxel arm experienced a statistically significant superior response rate and progression-free survival, and among patients without EGFR TK mutation patients in the gefitinib arm compared with carboplatin and paclitaxel experienced a statistically significant inferior response rate and progression-free survival. A phase III trial of platinum-based therapy with and without cetuximab in the first-line setting revealed improved OS in the cetuximab arm. A phase III trial of maintenance pemetrexed compared with placebo in patients who had not progressed after initial platinum-based therapy revealed an improvement in OS of patients in the pemetrexed arm with nonsquamous histology. In limited-stage small cell lung cancer, a phase III trial compared standard and high-dose prophylactic cranial irradiation and revealed no significant difference in the rate of brain metastases between the two treatment arms.     

ACR Appropriateness Criteria® postoperative adjuvant therapy in non-small cell lung cancer

Therapeutic options for postoperative adjuvant treatment for patients with non-small cell lung cancer (NSCLC) continue to evolve, and may include postoperative radiotherapy (PORT) and chemotherapy, alone or in combination. The use of platinum-based adjuvant chemotherapy has been demonstrated to confer an improvement in overall survival in patients with completely resected, stage N1 or N2 NSCLC, in several randomized trials and 2 meta-analyses. Consideration may also be given to adjuvant chemotherapy in patients with node-negative NSCLC, when the primary tumor is >4 cm, based on subset analyses of recent prospective studies. The precise role of PORT is less well defined. Older randomized studies indicated that the toxicity of PORT outweighed the potential improvement in local control, but studies using more modern radiation techniques show significantly reduced toxicity, inferring that select patients may benefit. Relative indications for PORT include the presence of mediastinal lymph nodes, positive surgical margins, and considerations with regard to the extent and type of resection. This study by the lung cancer expert panel of the American College of Radiology summarizes the recent evidence-based literature that addresses the use of postoperative adjuvant radiotherapy and chemotherapy in patients with NSCLC, illustrated with clinical scenarios. The sequencing of radiotherapy and chemotherapy is discussed, along with issues regarding radiotherapy dose and fractionation, and the appropriate use of intensity modulated radiation therapy and particle therapy.     

Neoadjuvant or adjuvant therapy for patients with resectable liver metastases

Curative resection of liver metastases from colorectal cancer is associated with high 5-year overall survival rates, making complete resection the goal of therapy for many patients. Improved outcomes in recent years have resulted in the application of increasingly aggressive multidisciplinary approaches for patients with metastatic disease. The addition of newer, more active chemotherapeutic regimens has prolonged patient survival in those with advanced disease and increased the number of patients eligible for surgical therapy. Furthermore, integration of chemotherapy with hepatectomy in patients with initially resectable disease offers the potential for improving survival beyond that seen with resection alone. Recent randomized studies have demonstrated a benefit of both adjuvant and neoadjuvant chemotherapy. However, questions regarding the optimal indications, regimen, and sequence of therapy remain. The use of neoadjuvant chemotherapy has potential advantages over postoperative adjuvant therapy, including improved patient selection, determining response to therapy, and achieving earlier delivery of systemic therapy. The disadvantages sometimes seen with neoadjuvant therapy include chemotherapy-associated hepatotoxicity and inability to identify resectable lesions. Ultimately, a therapeutic strategy that includes all aspects of multidisciplinary and multimodality care is required to select and treat this complex group of patients.     

Diagnosis and treatment of metastatic disease to the liver

A number of cancers present with synchronous or metachronous hepatic metastases. Historically, many of these patients were considered unresectable and were treated with either systemic chemotherapy or supportive care. Today, a variety of options exist for the management of hepatic metastases. Newer agents for systemic therapy continue to be introduced and are providing improved progression-free and overall survival and increased resectability of liver metastases. However, complete surgical resection of isolated hepatic metastases remains the optimal management for these patients. Surgical interventions can be offered to patients with hepatic-only metastases. Hepatic artery chemotherapy represents an adjunct for those patients undergoing resection and can improve survival. This benefit may be even more pronounced when combined with systemic chemotherapy. Newer generation biologic agents can improve results. New therapeutic modalities to treat lesions that are unresectable include ablative techniques such as radiofrequency ablation (RFA) and cryoablation. This article will examine modalities of diagnosis of hepatic metastases and highlight the data regarding hepatic resection for metastases of several types of primary cancers, the rationale for, and efficacy of, hepatic arterial chemotherapy, in both the postoperative adjuvant setting and in unresectable liver disease, and review the current literature for ablative techniques in the treatment of liver metastases.     

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.     

Surgical Resection of a Solitary Pancreatic Metastasis from Colorectal Cancer: A New Step to a Cure?

Isolated metastases to the pancreas from colorectal cancer (CRC) are very rare. We report a case of a 37-year-old man with a hereditary nonpolyposis CRC with a solitary metastasis to the pancreas who was treated with right hemicolectomy, neoadjuvant chemotherapy, complete surgical resection of the pancreatic metastasis, and adjuvant chemotherapy. After 12 months of follow-up, the patient remains free of disease. Differential diagnosis of isolated metastasis to the pancreas should be performed with pancreatic primary adenocarcinomas and neuroendocrine tumors. Symptoms and signs might be similar in these diseases: pain, weight loss, obstructive jaundice, and duodenal obstruction. Nevertheless, both primary and secondary tumors might be totally asymptomatic. Imaging techniques such as computed tomography, ultrasonography, magnetic resonance imaging, positron emission tomography, or endoscopic retrograde colangiopancreatography can provide relevant information about pancreatic lesions. However, it remains difficult to distinguish primary from metastatic pancreatic tumors. Although there is currently very limited experience with the surgical resection of isolated pancreatic metastases from CRC, it should be considered in selected patients with low surgical risk in order to prolong progression-free survival and overall survival. Additional chemotherapy is recommended.     

Selected benefits of thoracotomy and chemotherapy for sarcoma metastatic to the lung

To determine the benefit of aggressive surgical therapy, we studied 77 consecutive patients presenting to our sarcoma registry with pulmonary metastases. Detailed follow-up was available on all patients; the median follow-up of the 13 long-term survivors was 72 months from the date of diagnosis of the primary tumor. Survival of these 77 patients with metastatic disease was independent of the size, location, and histology of the primary tumor. Once metastases developed, survival of patients with pulmonary metastases was not influenced by the extent of surgical resection of the primary tumor or by the use of radiation therapy. Pulmonary metastases were initially treated with thoracotomy and metastasectomy in 34 patients. The median survival after thoracotomy was 26 months. Seven patients were alive more than 4 years after their diagnosis. Pulmonary metastases were treated with chemotherapy alone in 43 patients. Although the survival was shorter (median survival 14 months) in patients treated with chemotherapy, an objective response to chemotherapy was obtained in 13 (30%) patients. Four of these patients were alive 4 years after their diagnosis. These data demonstrate that both thoracotomy and chemotherapy are associated with long-term survival of patients with sarcoma metastatic to the lung. © 1993 Wiley-Liss, Inc.     

Patients with stage I non-small cell lung carcinoma at postoperative risk for local recurrence, distant metastasis, and death: implications related to the design of clinical trials.

PURPOSE: Patients with pathologically staged American Joint Committee on Cancer stage I (T1 N0 or T2 N0) non-small cell lung cancer have a favorable prognosis after complete surgical resection compared with patients with more advanced stages. Benefits of adjuvant therapy in this setting are unproved. However, there may be subgroups of patients with stage I disease at high enough risk for local recurrence to prompt consideration of adjuvant or neoadjuvant radiation therapy. Likewise, there may be subgroups of patients at high enough risk for distant metastasis to justify the evaluation of chemotherapy. METHODS AND MATERIALS: From 1987 through 1990, 370 patients undergoing gross total resection of non-small cell lung cancer had stage I disease and received no chemotherapy or radiation therapy as part of their primary treatment. These patients were the subject of a retrospective review to separate patients into high-, intermediate-, and low-risk groups with respect to freedom from local recurrence (FFLR), freedom from distant metastasis (FFDM), and overall survival by using a regression tree analysis. RESULTS: The 5-year rates of FFLR, FFDM, and survival were 85%, 83%, and 66%, respectively. Regression analyses revealed that the factors independently predicting for a poorer FFLR rate included fewer than 15 lymph nodes dissected and pathologically evaluated (p = 0.002) and the presence of a T2 tumor (p = 0.04). Factors independently predicting for a poorer FFDM rate included a maximal dimension greater than 5 cm (p = 0.02) and nonsquamous histology (p = 0.03). Factors independently predicting for a poorer survival rate included fewer than 15 lymph nodes dissected and pathologically evaluated p = 0.001) and a maximal dimension greater than 3 cm (p = 0.003). Regression tree analyses were used to separate patients into risk groups. CONCLUSION: Incorporating the aforementioned factors into regression tree analyses, three risk groups were identified with respect to FFLR. Two each were identified for FFDM and for survival. For each of these three end-points, the differences in outcomes for each risk group were found to be both statistically and clinically significant. These risk groups may be useful in the future design of phase III trials evaluating the use of adjuvant chemotherapy and radiation therapy in the stage I setting.     

Adjuvant Therapy in Combination with Resection of Colorectal Cancer Metastasis to the Liver or Lungs

Surgical resection is associated with prolonged survival for patients with limited lung or liver metastatic colorectal cancer. The benefit of resection of colorectal liver metastases is widely accepted. However, after complete resection of colorectal liver metastases, up to 70 % of patients develop recurrence. Oncosurgical strategies, including complete resection and chemotherapy, have been developed to improve oncological outcome and to reduce recurrence after resection of colorectal liver metastases. Chemotherapy in combination with liver resection can be administered before, after, or before and after the surgical procedure. Perioperative chemotherapy has been revealed to reduce the risk of recurrence and has been accepted as a standard of care for patients with resectable liver metastases. Research, including intensification of chemotherapy administered in combination with surgery, is ongoing to further improve outcomes for patients with resectable liver metastases. There are currently few data regarding the benefit of chemotherapy administered in association with resection of lung metastases from colorectal cancer. A large prospective trial is currently evaluating the benefit of resection of lung metastases from colorectal cancer.     

Surgical management of cerebral metastases from non-small cell lung cancer

AIMS AND BACKGROUND: The objective of the study was to assess the efficacy of surgical resection of solitary brain metastasis in patients with non-small-cell lung cancer. METHODS AND STUDY DESIGN: We report a retrospective analysis of 32 patients with single brain metastasis surgically excised at our hospital. All but one patient underwent postoperative whole brain radiation therapy. RESULTS: The median survival of patients was 12.5 months postoperatively (mean, 17 months), and the overall 1-year survival was 53%. Thirteen patients had recurrence of brain metastasis: 6 of 13 underwent reoperation for the recurrent lesion, and 1 of the 6 patients had a third craniotomy. Baseline characteristics, which significantly influenced survival, included age less than 60 years, tumor histology (ie, adenocarcinoma), and treatment of the primary lung cancer. The analysis did not yield any significant differences between treatment modalities. CONCLUSIONS: Our findings correspond well with those reported in the literature and suggest that surgical resection of single brain metastasis in patients with non-small cell lung cancer can improve survival over conservative management. Furthermore, surgical treatment of the primary tumor and the single brain metastasis, combined or not with radiotherapy and chemotherapy, represents an approach that merits further investigation with more patients and a prospective longitudinal design.