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.     

Nonsurgical therapy for stages I and II non-small cell lung cancer

For patients who have stages I and II non-small cell lung cancer (NSCLC) and who are unable or unwilling to undergo surgical resection, nonsurgical treatment modalities have been used with curative intent. Conventionally fractionated radiotherapy has been the mainstay of nonsurgical therapy; however, advances in technology and the clinical application of radiobiologic principles have allowed more accurately targeted treatment that delivers higher effective doses to the tumor, while respecting the tolerance of surrounding normal tissues. This article discusses nonsurgical approaches to the treatment of early-stage NSCLC, including several promising techniques, such as radiation dose escalation, altered radiation fractionation, stereotactic radiotherapy, and radiofrequency ablation.     

Risk assessment and adjuvant systemic therapy in resected stage II colon cancer

Adjuvant chemotherapy following surgical resection of stage III colon cancer has become the standard of care based on numerous large randomized trials that have demonstrated benefit in overall survival. For patients with stage II colon cancer, the picture is more uncertain. Although clinical trials have not reported a significant survival benefit for adjuvant chemotherapy in stage II disease, patients with certain high-risk clinical and pathologic features may warrant postoperative treatment. Molecular markers, such as 18q loss of heterozygosity and mi crosatellite instability, may also help to prognosticate patients with stage II colon cancer, although data supporting their role have been largely retrospective. The role of these markers in stage II disease is being prospectively investigated. Continued enrollment in clinical trials and further risk stratification will help clarify the optimal management of patients with stage II colon cancer.     

结肠癌术后辅助治疗的研究进展

结肠癌是消化道最常见恶性肿瘤之一。在过去的10年里,结肠癌的辅助治疗取得了巨大进步。虽然外科手术是治疗结肠癌的中流砥柱,但是辅助治疗也是增加结肠癌患者无病生存期和总生存期的一个重要方面。在接受根治性手术后的结肠癌患者中,约1／3的患者伴有区域淋巴结转移,1／4的患者虽不伴有区域淋巴结转移但存在高危复发因素。辅助治疗的作用就是消除微转移肿瘤沉积物,这种微转移沉积物可以增加癌症复发的机会。本文将对辅助化疗疗程、不同临床分期患者如何辅助化疗、老年患者的辅助化疗及国际上普遍存在的争议等方面的进展作一综述。     

Targeted agents for adjuvant therapy of colon cancer

Among patients with colorectal cancer (CRC) diagnosed in the United States, 37.2% are diagnosed with stage III and 27.9% with stage II disease. In locoregionally advanced CRC, surgery is the primary treatment modality and has a curative intent. The survival depends on the pathologic stage and varies from 30%-60% for stage III to 60%-80% for stage II. However, as much as 40%-50% of patients will relapse and require additional treatment of the disease. Clinical failure after resection of CRC is predominantly secondary to the clinical progression of previously undetected distant metastatic disease. Until very recently, the absolute benefit for survival obtained with adjuvant therapy compared with control was about 6%. Introduction of oxaliplatin in the adjuvant setting has shown a reduction of 23% in the risk of relapse when compared with 5-fluorouracil alone (MOSAIC). Recent phase III studies have shown that targeted agents improved survival in patients with advanced-stage CRC. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, is the first antiangiogenic drug to show improved efficacy when used in combination with irinotecan and oxaliplatin for first- and second-line treatment of CRC. Cetuximab, another monoclonal antibody targeting epidermal growth factor receptor, has shown efficacy in third-line therapy and promising results in first-line phase II studies. There is great interest in whether the biologic agents bevacizumab and cetuximab can improve survival in the adjuvant-therapy setting. This article reviews the adjuvant therapy for colon cancer and discusses the potential role and current trials involving the targeted agents.     

Optimizing adjuvant therapy for colon cancer: Ongoing investigations

In 2004, oxaliplatin plus 5-fluorouracil (5FU) and leucovorin (LV) supplanted 5FU/LV as the standard of care for adjuvant therapy of node-positive colon cancer. Data from recently presented phase III clinical trials fail to show a similar benefit for adjuvant irinotecan-5FU/LV over 5FU/LV alone. Current investigations focus on further refining the optimal combination chemotherapy regimen, and incorporating biologic agents into adjuvant therapy of stage II and III colon cancer. In the future, stage-independent prognosticators and markers predictive of chemotherapy response and toxicity may allow for patient-specific selection of more effective and less toxic adjuvant therapy.     

Noninterferon-based adjuvant therapy for high-risk melanoma

High-dose interferon is the only treatment approved by the FDA for adjuvant therapy of melanoma. However, its efficacy in this setting is questionable and its administration is associated with considerable toxicity. Many new agents are being tested clinically that hold the promise of greater efficacy and less toxicity but none of these have yet shown efficacy in controlled trials. These include biologics such as vaccines, cytokines, monoclonal antibodies, gene transfer, cellular therapies and angiogenesis inhibitors as well as chemotherapy combinations.     

Noninterferon-based adjuvant therapy for high-risk melanoma

High-dose interferon is the only treatment approved by the FDA for adjuvant therapy of melanoma. However, its efficacy in this setting is questionable and its administration is associated with considerable toxicity. Many new agents are being tested clinically that hold the promise of greater efficacy and less toxicity but none of these have yet shown efficacy in controlled trials. These include biologics such as vaccines, cytokines, monoclonal antibodies, gene transfer, cellular therapies and angiogenesis inhibitors as well as chemotherapy combinations.     

The impact of adjuvant therapy for patients with high-risk diffuse WHO grade II glioma

Despite recent randomized, prospective evidence supporting use of RT and chemotherapy (CRT) for high-risk low-grade gliomas (LGG), many patients have historically received RT alone, chemotherapy alone or observation postoperatively. The purpose of this study is to evaluate outcomes for historical treatments in comparison to CRT for high-risk diffuse WHO grade II glioma patients. Records from 309 adults with WHO grade II glioma (1997–2008) eligible for RTOG 9802 (incomplete resection/biopsy or age ≥40 years) were retrospectively reviewed. Kaplan–Meier estimates were used for progression-free survival (PFS) and overall survival (OS). The Cox proportional hazards model was used for estimates of risk ratios for univariate and multivariate analyses. Median follow-up was 10.6 years. Adjuvant treatments included radiotherapy (RT) alone (45%), observation (31%), CRT (21%) and chemotherapy alone (3%). Non-astrocytic histology, TERT promoter mutation, 1p/19q codeletion and extensive resections were associated with improved PFS and OS on univariate analysis (all p?<?0.05). IDH mutations and adjuvant CRT was associated with improved PFS (all p?<?0.05). On multivariate analysis, histology, molecular grouping and extent of resection were significantly associated with PFS and OS. In addition, multivariate analysis revealed that CRT was associated with improved PFS and OS compared with RT alone, and improved PFS compared with observation. This study confirms the benefit of adding chemotherapy to RT compared with RT alone or observation. These findings emphasize the need for aggressive treatment in patients with high-risk LGG.     

Breast-conserving surgery and selective adjuvant radiation therapy for stage I and II breast cancer.

In this report we update our experience with selective adjuvant radiotherapy (XRT) following breast-conserving surgery (BCS) for early breast cancer. Of 150 evaluable private breast cancer patients treated by BCS since 1975, 83 were offered the option of foregoing adjuvant XRT because their primary disease met four pathological criteria: primary tumor less than or equal to 2.5 cm; adequate resection margins; no intramammary vascular, lymphatic, or perineural invasion by tumor; and minimal or no associated in situ cancer. Of the 67 patients who chose not to have XRT, four have developed local (breast) tumour recurrence at 80 months' median follow-up (5-year local recurrence rate 6.4% by Kaplan-Meier analysis). These findings are discussed in light of other series in which patients were carefully selected for BCS without XRT, and the observations of large randomized trials and unselected series of patients. We conclude that adjuvant XRT is not always necessary following BCS. The most valuable contribution of XRT to breast-conserving therapy is that a much larger proportion of breast cancer patients can be considered for conservative locoregional surgery than would otherwise be reasonable.     

Epirubicin versus CMF as adjuvant therapy for stage I and II breast cancer: a prospective randomised study

We compared a relatively short regimen of monochemotherapy with epirubicin versus polychemotherapy with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) as adjuvant treatment for stage I and II breast cancer patients. 348 patients with oestrogen receptor negative (ER-) node negative and ER- or ER+ node-positive with <10 nodes were accrued. CMF was given intravenously (i.v.) on days 1 and 8, every 4 weeks, for six courses; epirubicin was given weekly for 4 months. Postmenopausal patients received tamoxifen for 3 years. The primary endpoints were overall survival (OS), relapse-free survival (RFS) and event-free survival (EFS). Outcome evaluation was performed both in eligible patients and in all randomised patients according to the intention-to-treat principle. 8 randomised patients were considered ineligible. At a median follow-up of 8 years, there was no difference in OS (Hazard Ratio (HR)=1.11, 95% Confidence Interval (CI): 0.77-1.61, P=0.58), EFS (HR=1.14, 95% CI: 0.78-1.64, P=0.48), and RFS (HR=1.14, 95% CI: 0.8-1.64, P=0.48) between the two arms for all of the patients. At 8 years, the RFS percentages (+/-Standard Error (S.E.)) were 65.4% (+/-4%) in the CMF arm and 62.7% (+/-4%) in the epirubicin arm; for EFS these were 64.2% (+/-4%) for CMF and 60.8% (+/-4%) for epirubicin, respectively. A significant difference in RFS (P=0.015) was observed in patients with 4-9 positive nodes in favour of the CMF arm. Toxicity in the two arms was superimposable except for more frequent grade 3 alopecia in the epirubicin-treated patients (P=0.001). Overall, at a median follow-up of 8 years, there were no differences between the two arms in terms of OS, EFS and RFS.     

Refining adjuvant therapy for non-metastatic colon cancer,new standards and perspectives

Colon cancer is the third most frequent cancer in males and the second in females. Approximately 75% are diagnosed at a localized stage. Recurrence occurs in 30% of patients when there is nodal involvement (stage III) due to micrometastatic spreading. To date only chemotherapeutic drugs such as fluoropyrimidines or oxaliplatin have proven effective to kill this residual disease and are currently recommended by scientific societies. To improve patient management in the near future, recent research has focused on new ways of using currently available agents, tools to better define each individual patient prognosis more clearly so as to tailor adjuvant treatment, and molecular profiling to identify specific subgroups of patients with tumors that may benefit from specific therapeutic approaches. In this review, we will focus on current scientific knowledge on adjuvant treatment in localized colon cancer, the duration and timing of adjuvant therapy and the perspectives for better selection of patients who will benefit from adjuvant treatments.