Adjuvant interferon-alpha for melanoma revisited: News?from?old?and?new?studies

Currently the data from 12 randomised phase III trials investigatingthe role of interferon-alpha (IFN-2a) in patients with stageII–III high-risk melanoma are available. The most prominentdifferences between these trials concern the dose of IFN-2a, theduration of IFN-2a administration, and the stage of disease. Some ofthese trials have not yet reached maturity, but despite this thepositive results from some immature trials have attracted considerableattention. When only data from mature trials is considered, one mayconclude that the use of high-dose IFN-2a does prolong disease-freesurvival (DFS) but not overall survival (OS). Combined data fromlow-dose IFN-2a trials does not suggest a benefit in either DFS or OS.A trial with intermediate-dose IFN-2a is still immature. Thereforecurrently the routine use of IFN-2a cannot be recommended outside thescope of clinical trials.     

Scan? Cure? Sure!

Presentation of The Case

A 61-year-old man undergoes a sigmoid colectomy for a T3N1 (two of 18 nodes) adenocarcinoma of the sigmoid colon. He recovers well and receives 6 months of adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) uneventfully. At his first follow-up visit, the oncologist recommended every 3 month visits for a physical, liver function tests, and carcinoembryonic antigen (CEA) measurement; every 6 month chest, abdomen, and pelvic computed tomography (CT) scans for 3 years; and aspirin, vitamin D supplementation, and exercise. Is CT scanning appropriate in the follow-up of colon cancer patients? (This case was presented at Massachusetts General Hospital Cancer Center.)

• Oncologist. 2011 Feb; 16(2): 254–256.
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2011 Feb; 16(2): 254–256. doi: 10.1634/theoncologist.2011-0014

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Richard M. Goldberg

Richard M. Goldberg

University of North Carolina at Chapel HillFind articles by Richard M. GoldbergAuthor information Copyright and License information DisclaimerUniversity of North Carolina at Chapel HillCopyright notice Open in a separate windowRichard M. Goldberg, M.D.Just recently, I reorganized my talking points about management of metastatic colorectal cancer. Now I focus those conversations, whether they occur in a lecture hall or a clinic exam room, around an AJCC (American Joint Committee on Cancer) unsanctioned but pragmatic new staging system, which I will call “UNC.” With multidisciplinary input at the University of North Carolina (also, by coincidence, UNC), we sort patients into those “unlikely (U)” to undergo resection because of the extent of their metastatic disease or their comorbid conditions that make the risk of surgery prohibitive, those who can undergo resection “now (N),” and, those who “could (C)” after a response to medical treatment potentially undergo resection. We formulate management strategies that differ according to those categories. Currently, multidisciplinary teams can realistically offer the possibility of long-term disease-free survival to a subset of patients who fit into the N or C subcategories. How do we segregate patients into those categories? We book them an appointment for a CT scan because they seldom have symptoms or physical findings that reliably tell us how extensive their disease is [1].After patients with stage II or III disease complete their initial therapy, it is common practice to do interval CT scans, CEAs, and colonoscopies aimed at early detection of recurrent disease and new primary tumors. Guidelines issued by the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the Cochrane Collaboration reinforce this practice [2–4]. Are we fooling ourselves and our patients about the value of this approach in terms of lives saved or prolonged and money spent? My fiscally conservative crimson (Harvard''s colors) friend and colleague Dr. Ryan suggests that we are and, from my vantage point on the opposite side of the color wheel (UNC''s team color is sky blue), I disagree. Is there evidence on which to base a CT scan-based surveillance protocol?The natural history of colorectal cancer stands out among solid tumors. Cohen and colleagues studied circulating tumor cells (CTCs) in patients with metastatic disease, proving that with current technology they could readily identify CTCs in a 10-ml aliquot of blood [5]. Yet in many patients, most of these potential seeds never grow and scans detect one or a few metastatic lesions. In patients with pancreatic cancer, resection of metastases is not curative. In many series, resection of limited hepatic and pulmonary metastases in colorectal cancer patients leads to a 30%–60% likelihood of long-term disease-free survival and to a substantial 5-year survival rate, even when surgery and drug therapy prove not to be curative [6]. Unfortunately, a substantial number of patients will subsequently relapse, some rapidly, and we need to discover molecular/genetic profiles that can help predict who among the patients with a single or small number of scan-identified lesions will likely benefit from curative resection and who will not. We hopefully can spare patients the pain and society the expense of fruitless surgeries once those data are available.An expert multidisciplinary committee that included several individuals whose prior published work included recommendations against routine surveillance CT scanning (Loprinzi, Virgo) wrote the most recent 2005 ASCO guidelines that endorse follow-up CT scan screening for patients with stage II and III colorectal cancer [2]. An exhaustive review of the literature available at that time convinced the panel of the value of scans. The review included three meta-analyses, all of which they classified as “highest quality” using the metrics defined by the Oxmann-Guyatt Overview Quality Questionnaire. These three meta-analyses reported a 20%–33% reduction in the risk of death from all causes in the groups of patients who had scans as a routine part of follow-up [4, 7, 8]. Interestingly, this reduction in the odds of death is nearly identical to that reported by Moertel and colleagues for adjuvant therapy of stage III colon cancer [9]. The data on the benefit of adding oxaliplatin to fluorouracil-based therapy provides a lesser incremental benefit [10]. Presumably, Dr. Ryan does offer adjuvant therapy with FOLFOX to his patients with stage III colon cancer after resection. Finally, I am having a hard time with the validity of the cost estimates that Dr. Ryan offers. In summary, I believe the data support CT scan surveillance for patients with stage II or III colorectal cancer and the management of those patients found to have recurrent disease using the “UNC” approach.     

Rectal cancer adjuvant therapy controversies: When? What? Why?

Although the need for adjuvant therapy in high-risk rectal cancer is widely accepted, controversies continue regarding timing, mode, and agents employed. The current recommended practice and its scientific basis are reviewed. Studies of induction therapy are discussed. Evidence of efficacy of new anticancer agents and modes of drug delivery are presented.     

Sekund?rpr?vention von Hauttumoren

The aim of secondary prevention of skin cancer is to diagnose neoplasia at early non-invasive growth phases which are not associated with the risk of metastasis. Secondary prevention is achieved by screening programs which allow identification of patients at high risk for skin cancer and by improvement of diagnostic accuracy. This can be partially achieved by the application of dermoscopy which improves the diagnostic accuracy by more than 35%. A consistent treatment of precursor lesions, such as solar keratoses or Bowen??s disease can reduce the rate of squamous cell carcinoma especially in patients at risk. An early diagnosis of recurrent disease in skin cancer patients can be achieved by a standardized risk profile adapted follow-up.     

什么该吃?什么不该吃?

可适量摄取的食品1.日本国立癌症预防研究所通过对40多种蔬菜抗癌成分的分析及抑癌试验,从高到低排出对肿瘤有明显抑制效果的蔬菜,它们是:熟红薯、生红薯、芦笋、花椰菜、卷心菜、芹菜、茄子、青椒、胡萝卜、金针菜、荠菜、西红柿、大葱、大蒜、黄瓜、白菜。     

Detection of chromosomal abnormalities in soft tissue sarcomas: which sarcomas? Which abnormalities? How? Why?

During the last 10 years, molecular testing of soft tissue tumors has become increasingly important, not only in the diagnostic approach of these lesions, but also regarding their prognosis and pathogenesis. A subset of soft tissue sarcomas bear chromosomal abnormalities including reciprocal translocations, deletions, mutations and amplifications, which turned out to be histotype specific. Beside their diagnostic value in sarcoma typing and subtyping (always in an appropriate clinical and histologic context), some of these abnormalities may also impact on treatment response and/or on prognosis. The aim of this review is to provide an overview of the most informative soft tissue sarcoma chromosomal abnormalities, and to give some clues about why and how we should detect them. Some sarcoma types (Ewing sarcoma, rhabdomyosarcomas, synovial sarcoma, well-differentiated/dedifferentiated and myxoid liposarcomas, gastrointestinal stromal tumors--GIST, malignant rhabdoid tumor) will be studied in more detail and the potential implication of these abnormalities in tumor genesis, growth, and maintenance will be briefly discussed.     

Chemotherapy for Stage IV Non-Small Cell Lung Cancer: Protocol Versus Nonprotocol? Is Noninvestigational Treatment Worthwhile? Patient Selection? Which Regimen? What's Next?

The results of selected chemotherapy trials and philosophical considerations regarding the role of chemotherapy in Non-Small Cell Lung Cancer are discussed in this review. The issue of treating patients within a clinical or with a "standard regimen" is addressed. In addition, the survival results of randomized trials in which chemotherapy was compared with supportive care and the related quality of life and economic concerns are reviewed. Physicians' attitudes regarding treating advanced non-small cell lung cancer patients as well as the questions of patient selection and the choice of regimen including the consideration of single versus combination regimens are discussed. The results of single agent phase II trials that identified new agents with response rates >/=15%-paclitaxel, docetaxel, vinorelbine, gemcitabine, CPT11-are described, and their implications for the design of new clinical trials are discussed.     

预防注射抗癌?

从流行病学研究获悉,日光照射引起的婴幼儿皮肤晒斑是发生恶性黑色素瘤的危险因素之一。此外,遗传素质也与之有关。至于日晒在多大程度上可以引起这一恶性肿瘤,或者是通过削弱免疫系统而间接地促进其发生,目前尚在研讨中。事实上是,德国每年约有8000人罹患这一肿瘤,患者的平均年龄约为50岁,与其他癌症相比,年龄较低。黑色素瘤的早期发现对于疾病的经过和预后都具有极其重要的意义。一旦发生了转移,其预后将极端变坏。在已确诊的黑色素瘤中约有20％将发生转移。     

Tamoxifen--what next?

Most patients with advanced breast cancer (ABC) ultimately die due to disease progression. Consequently, treatments for ABC are predominantly palliative in nature and, therefore, the tolerability profile of a given treatment is particularly relevant in these patients. While cytotoxic chemotherapy and endocrine therapy exhibit efficacy in hormone-sensitive, advanced disease, it is endocrine therapy that combines efficacy with minimal acute toxicity. Tamoxifen has been the chosen endocrine therapy for postmenopausal, hormone-sensitive, ABC for over 20 years. More recently, new endocrine agents with different mechanisms of action from tamoxifen have been introduced. Evidence indicates that the aromatase inhibitors anastrozole (Arimidex; AstraZeneca; Wilmington, DE), letrozole (Femara; Novartis Pharmaceuticals Corp.; East Hanover, NJ) and exemestane (Aromasin; Pharmacia Corp.; Peapack, NJ) offer superior efficacy and tolerability to tamoxifen in the first-line treatment of postmenopausal, hormone-sensitive ABC. Similarly, after tamoxifen failure, fulvestrant (Faslodex; AstraZeneca), a new estrogen receptor (ER) antagonist that downregulates the ER, is at least as effective as anastrozole, is well tolerated, and is not cross-resistant with tamoxifen. Unlike tamoxifen, fulvestrant has no known agonist effects. The sequential use of such agents may prolong the time during which endocrine therapies can be used, thereby avoiding the more acute toxicities associated with cytotoxic chemotherapy. Indeed, a series of studies has shown that this sequential use is a relevant, active, and well-tolerated option. Establishing the comparative efficacies and optimal sequences that incorporate the newer endocrine agents will be central in determining the future role of hormonal therapy in ABC; the results of this work will determine the relative place of tamoxifen in what is a rapidly changing therapeutic environment.     

恶性肿瘤知多少?

据北京市肿瘤防治研究办公室监测资料显示,自上世纪90年代起,首都北京的恶性肿瘤发病率和死亡率均呈现明显上升趋势.2010年北京市户籍人口共报告恶性肿瘤新发病例37,795例,发病率为301.93/10万,比2009年(297.04/10万)上升1.6%.2007～2010年,癌症超过了心脑血管疾病,连续4年成为北京市居民的首位死因.2010年北京市男性恶性肿瘤发病前五位是肺癌、结直肠癌、肝癌、胃癌和食管癌,女性恶性肿瘤发病前五位是乳腺癌、肺癌、结直肠癌、子宫体癌和甲状腺癌(见上图),癌谱排序已呈现类似发达国家的变化趋势.