Surveillance and early diagnosis of colorectal cancer

Colorectal cancer is a major health problem in western countries such as the United States. The annual incidence of more than 130,000 new cases, and the annual mortality of more than 60,000 people justifies a consideration of efforts for its control. New concepts of risk, better understanding of the adenoma-adenocarcinoma natural history, and new screening and diagnostic technology have provided a basis for possible preventive approaches. Trials are in progress evaluating the fecal occult blood test and sigmoidoscopy screening tests, and colonoscopy as a diagnostic and surveillance test. Evaluation of data from the trials requires many considerations regarding bias and validity. Although the data from screening trials appear to be promising, they are still preliminary. In the interim, guidelines have been proposed for screening strategies related to average risk and high risk groups. Considerably more work will be required in order to provide the scientific basis for the control of large bowel cancer. In addition, efforts will have to be directed toward the effective communication of new concepts, data and techniques to the majority of physicians who interact with the at-risk population. Efforts will also have to be directed to the public at large to enhance their compliance with the approaches to increase their awareness of colorectal cancer as an important disease and to eliminate their misconceptions. Finally the cost effectiveness of various screening strategies will have to be examined once data indicates a benefit of such approaches.     

循环肿瘤细胞在早期肺癌诊疗中的研究进展

循环肿瘤细胞(circulating tumor cells, CTCs)作为液体活检的一种重要类型,在肺癌的筛查诊断、疗效评估、术后监测与预后判断等方面显示出越来越丰富的临床价值.随着对肺癌高危人群筛查工作的进展,大量肺小结节患者被检出,但是肺小结节不等于肺癌,而且据统计良性比例达90%-95%,这使得该部分患者在首次就诊时的良恶性鉴别诊断成为临床医生面临着的新的机遇与挑战.CTCs检测技术的不断进步与完善,是否可以在早期肺癌的鉴别诊断中发挥更大的作用,此外,它是否对早期肺癌手术治疗时的操作具有指导意义,这还需要进一步科研探索,以期将来实现临床转化.     

Diagnostic imaging--recent progress

Current advances in the diagnostic imaging for lung cancer includes multidetector-row CT (MDCT), lung cancer screening using low-dose MDCT and fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. There is no question about the clinical usefulness of MDCT, and the further development of the hardware and the software of MDCT will open new horizons for CT diagnosis. PET is not an alternative modality to CT but a supplementary one, which adds metabolic information to the morphology. Recently, experimental research on the refraction imaging of human lung specimens has been performed with synchrotron radiation. With progressive refinement, this technique may come to have some practical purpose in diagnosing lung cancer in vivo.     

Lung cancer screening

Advances in imaging technology have ushered in a new era for lung cancer screening in high-risk individuals using computed tomographic (CT) scans. Although most published studies are nonrandomized observational cohorts of volunteers, the ability of CT scans to detect early stage lung cancer is undisputable. What is unresolved is the ability of spiral CT screening to affect lung cancer-related mortality. A large randomized trial sponsored by the National Cancer Institute to address this question is currently under way. Genomic and proteomic approaches promise to complement the ability of spiral CT to detect early lung cancer in the next few years. Currently, the decision to screen for lung cancer should involve a careful discussion with the individuals involved about the potential advantages, costs, and drawbacks of the approach.     

非小细胞肺癌循环核酸的研究进展

对于肺癌患者临床前期和无症状期,临床诊断往往缺少最有效的无创性检测方法。非小细胞肿癌(NSCLC)患者血循环中核酸含量明显高于正常人,研究证实其抗酸来源于肿瘤细胞,并且与原发肿瘤有着结构或功能上的某些一致性,因此循环核酸对肿瘤的早期发现和早期诊断及治疗都具有重要价值。近年随着细胞分子生物学技术的发展,循环核酸的检测成为可能,这方面的研究也成为热点,本文综述国内外关于NSCLC的循环核酸研究进展。     

肺癌的早期诊断

肺癌已成为人类癌症死亡的主要原因之一,5年生存率仅10％。既往应用胸部X线和痰细胞学进行筛查和早期诊断的研究没有达到诊断筛查的目的－－肺癌死亡率的下降。随着新技术的发展,人们对肺癌筛查重新产生了兴趣。本文回顾了肺癌早期诊断最新进展,有低剂量CT、液基细胞学技术、荧光内镜和分子病理学等方面。     

A blueprint for cancer screening and early detection: Advancing screening’s contribution to cancer control

From the mid-20th century, accumulating evidence has supported the introduction of screening for cancers of the cervix, breast, colon and rectum, prostate (via shared decisions), and lung. The opportunity to detect and treat precursor lesions and invasive disease at a more favorable stage has contributed substantially to reduced incidence, morbidity, and mortality. However, as new discoveries portend advancements in technology and risk-based screening, we fail to fulfill the greatest potential of the existing technology, in terms of both full access among the target population and the delivery of state-of-the art care at each crucial step in the cascade of events that characterize successful cancer screening. There also is insufficient commitment to invest in the development of new technologies, incentivize the development of new ideas, and rapidly evaluate promising new technology. In this report, the authors summarize the status of cancer screening and propose a blueprint for the nation to further advance the contribution of screening to cancer control.     

Chemotherapy for prostate cancer: implementing early systemic therapy to improve outcomes

Prostate cancer remains a significant health concern for men in the USA as it is a leading cancer diagnosis and a cause of death. With the use of prostate-specific antigen or screening, a stage migration has occurred with an increase in the number of men diagnosed with early-stage disease. The optimal primary management of these men is evolving, but despite adequate local treatment a significant percentage will develop either biochemical or clinical evidence of recurrent disease. Several criteria for risk stratification have been developed, thus, improving the ability to identify a high-risk population. Small studies have been reported demonstrating the feasibility of neoadjuvant or adjuvant chemotherapy in conjunction with either radiation or radical prostatectomy in this high-risk population, and large phase III studies are ongoing. With the advent of life-prolonging chemotherapy in the hormone-refractory setting, attention must now also be given to early-stage disease so as to develop multi-modality approaches with the hope of increasing survival and ultimately providing a cure.     

Methodological issues in the economic analysis of cancer treatments

Cost-effectiveness analysis may be applied to the full range of interventions that make up a cancer service, including screening programmes and early treatments, diagnostic test and referral processes, surgery, radiotherapy, chemotherapy and palliative care. Numerous methodologies have been employed within existing models of cancer interventions. However, not all methodologies are equal; inappropriate modelling approaches may bias cost-effectiveness results. Generic guidelines for good practice in decision-analytic modelling provide a useful basis for critically appraising cost-effectiveness models, yet explicit consideration of a range of cancer-specific issues is required to avoid bias in cost-effectiveness results. These cancer-specific issues include the appropriate representation of relevant costs and health effects associated with unplanned treatments for metastatic disease administered beyond disease progression, the appropriate extrapolation of long-term outcomes and resources from clinical trials, assumptions concerning the nature of the event hazard function beyond the duration of the trial, and relationships between surrogate outcomes and final outcomes.     

Lung cancer screening

The result of a lung cancer screening program should be fewer lung cancer-specific deaths in the screened population. studies evaluating chest imaging as a screening tool for lung cancer have not shown a reduction in lung cancer-specific mortality to date. The ability of institutions using chest imaging to meet the criteria for successful screening programs has also been debated. Contentious issues include the presence of an overdiagnosis bias, the ability to find preclinical disease at a curable point in time, the amount of pseudodisease identified, and the cost-effectiveness of screening programs. Current guidelines remain vague as randomized trials are being completed and technologic advances are occurring. The ultimate face of a successful lung cancer screening program is yet to be defined.     

Constitutional polymorphisms of prostate cancer: prognostic and diagnostic implications

Prostate cancer is the most common cancer diagnosis in men. While often perceived as a slow, indolent malignancy, prostate cancer trails only lung cancer among cancer-related mortality in men. Current diagnosis and treatment algorithms are plagued by overdiagnosis of non-lethal indolent prostate cancer with no proven means to predict, detect, and prevent aggressive lethal prostate cancer in men most at risk. These challenges are particularly concerning for African-American men who demonstrate increased rates of prostate cancer incidence and mortality when compared to other ethnic groups. With the completion of the human genome project, technology and techniques now exist to differentiate cancer from normal tissues based on the expression patterns of thousands of genes assessed simultaneously on a single microarray gene 'chip'. This platform has greatly improved our understanding of genes that regulate tumor behavior once cancer is established. Microarrays can also be utilized in patients without cancer to determine which patients are at high risk for tumor development and in need of rational prevention strategies. Constitutional single nucleotide polymorphisms (SNPs) are one source of genetic variation and may serve as a means to identify these high-risk individuals. SNPs are single nucleotide base pair changes within a gene which occur in one percent or more of the population. SNPs can contribute to a disease state by altering the function of a protein encoded by a gene without affecting gene expression. This review will examine the current understanding of constitutional SNPs associated with prostate cancer carcinogenesis, highlight two current diagnostic array platforms and discuss implications for future prevention and screening programs.     

Unanswered questions in screening for prostate cancer

Prostate cancer fulfils some of the conditions required of a disease that might be managed by population screening. In a cohort of 50- to 60-year-old men, carrying out a rectal examination and prostate specific antigen (PSA) test will detect clinically suspicious areas within the prostate in approximately 5%, and approximately 10% will have a raised PSA. We are however unsure which of the prostate cancers that are known to be present in approximately 30-40% of men aged over 60 years will be detected. Eventually after such screening, around 4% of men with an otherwise normal prostate will be found to have prostate cancers. The use of rectal examination may increase the number of tumours found, but will reduce compliance. The use of free/total PSA ratios will reduce the number of unnecessary biopsies at the expense of missing some tumours. Of more concern, we remain uncertain how effective aggressive local treatment is in altering the natural history of the disease. The risk of a 50-year-old man with a 25 year life expectancy of having microscopic cancer is 42%, of having clinically evident cancer is 9.5%, and of dying of prostate cancer 2.9%. Only a small proportion of cancers known to be present become clinically evident: more men die with prostate cancer than of it. Screening will identify some men with cancer who will not benefit from treatment. It is unclear whether screening would be followed by a reduction in morbidity and mortality. Recent data suggest a screening effect has been observed in the USA with: an increase in incidence, a decrease in men with distant metastases. The small decrease in mortality recently observed (many times smaller than the increase in incidence) may be confounded by inappropriate 'attribution' of cause of death, the detection of men with better prognosis distant metastatic disease responsive to hormonal ablation and changes in social factors such as diet. Future changes may incorporate molecular markers that might aid identification of men best treated aggressively because of a risk of progression. Tests to identify genetic pre-disposition may also allow targeted screening. New treatments and early chemoprevention or dietary strategies will again shift the ground on which these arguments are being rehearsed. The most urgent evidence required concerns the effectiveness of treatment strategies.     

Translational research in lung cancer

Recent research advances in cancer and molecular biology have furthered our understanding of the etiology and natural history of lung cancer. Through translational research, a growing understanding of the molecular changes that underlie cancer progression has contributed to the development of novel molecular approaches for early detection, further defining prognosis, refining treatment schedules, identifying new therapeutic targets, and identifying patients at risk for treatment-related toxicity from aggressive therapy, such as pneumonitis and esophagitis. In this article, we review progress in molecular/gene screening and prognosis, and we present a clinical study, based on preclinical research, in which we apply low-dose radiosensitizing paclitaxel for locally advanced non-small-cell lung cancer (NSCLC); this resulted in superior local tumor control while keeping treatment toxicity low. We also review progress made in identifying cytokines: interleukin [IL]-1alpha, IL-6, and transforming growth factor [TGF] beta as markers for lung cancer treatment-related radiation pneumonitis. Finally, we summarize different targeted therapy approaches and discuss their application to clinical trials. Irrespective of the slow progress toward clinical improvements, we have gained much knowledge through translational research using new molecular and biologic technology. We believe that knowledge of lung cancer biology will continue to provide the foundation for future improvements in lung cancer treatment.     

Lung cancer detection. Results of a randomized prospective study in Czechoslovakia

A randomized prospective study of lung cancer detection was begun in 1976 to evaluate semiannual screening by radiologic and sputum cytologic study in comparison to screening at a 3-year interval, and to no screening. In a high-risk population of 6364 men (aged 40 to 64 years), the initial prevalence of lung cancer was 0.28% (18 cases), the annual incidence was 0.35% per year (66 cases during 3 years), the proportion of Stage I cases was 31% (26/84), and Stage II was 17% (14/84), "curative" resections were 27% (23/84), and 5-year survival was 23% (19/84). The study confirmed the ability of radiologic screening to detect lung cancer at an earlier stage when treatment by resection can be accomplished. The fate of a high-risk population submitted to screening was better than that of a population with no screening where lung cancer was discovered by symptoms, accidental x-rays, or at autopsy. A matter of lesser importance was the frequency of screening. The absolute numbers of 5-year survivors detected by screening were practically the same for either compared screening frequency.     

Role of salvage radical prostatectomy for recurrent prostate cancer after radiation therapy.

Patients with isolated local recurrence of prostate cancer after radiation therapy may potentially be cured of their disease by salvage radical prostatectomy (RP). The stage-specific 5-year cancer-control rates of salvage RP resemble those of standard RP. However, the ability to effectively administer salvage treatment to patients with radiorecurrent disease is compromised by the lack of diagnostic tests with sufficient sensitivity and specificity to detect local recurrence at an early stage while it is amenable to local salvage therapy. By the time biochemical recurrence is declared using the current American Society for Therapeutic Radiology and Oncology definition, the majority of patients have advanced local disease, precluding successful local salvage therapy. When salvage RP is performed at prostate-specific antigen levels of 10 ng/mL or less, an estimated 70% of patients are free of disease at 5 years. With better patient selection and technical modifications, the morbidity associated with salvage RP has improved substantially. Rates of urinary incontinence and anastomotic stricture are acceptable, although one third of patients will experience these complications. Salvage cryotherapy is a minimally invasive alternative to salvage RP, but cancer-control rates appear to be inferior and it does not provide a clear advantage over salvage RP in terms of reduced morbidity. Patients with local recurrence after radiation therapy are at increased risk of metastatic progression and cancer-specific mortality. Currently, salvage RP represents the only curative treatment option for these patients. Salvage RP may favorably alter the natural history of biochemical recurrence after radiation therapy, but it must be instituted early in the course of recurrent disease to be effective.     

Lung cancer screening with spiral CT

Lung cancer is the main cause of death from malignancies due to the high prevalence and adverse prognosis when diagnosis is established in symptomatic patients. With early diagnosis, survival is far better; this led to perform some trials of screening in subjects at high risk with chest X-ray since 1970 but outcomes were contrasting. The technological evolution with the introduction of spiral CT and low dose techniques in the last decade led to a new interest in lung cancer screening. Numerous trials were performed and several diagnostic algorithms based on the dimensional and densitometric analysis of CT-evidenced nodules were designed. In spite of the encouraging outcome achieved so far, the high rate of false positives, the high costs and the use of ionizing radiation advise caution at least until a decreased mortality rate from lung cancer is evidenced.     

Small Cell Lung Cancer: The Influence of Dose and Treatment Volume on Outcome

The treatment of small cell lung cancer is clearly enhanced by the addition of radiation therapy. Survival increases modestly while local thoracic failure as first site of progression is reduced from approximately 60% when chemotherapy alone is used to 30% after combined modality therapy. The variables of radiation dose and treatment volume seem to be important in the successful management of this disease. Local chest control appears to increase as doses are escalated from low levels (25 Gy) to moderate levels (45 to 50 Gy(. With about one third of patients experiencing local chest progression, one can speculate that higher radiation doses might be of value. However, at this time there is no proof that increased dose or dose intensity bears out this promise. Indeed, increasing dose intensity of radiotherapy, eg, twice-daily treatment, increases esophagitis, perhaps reduces local failure, but has not improved overall survival. Using larger total doses or altered fraction schemes must still be considered to be under investigation. To increase dose in a safe manner, reduction in the volume covered by radiation portals will likely need to take place. Modern trials suggest that prophylactic treatment of the radiographically or clinically negative contralateral hilum and/or supraclavicular nodal regions may not be necessary for survival or local control. Importantly, reducing treatment volumes may permit increasing doses without exceding normal tissue tolerance. Also, reduced volumes pave the way for further clinical trials that improve radiation dose delivery by better target definition and more conformal therapy.     

Early lung cancer detection and treatment strategies

Lung cancer is the leading cause of cancer deaths in both men and women in the United States. The majority of lung cancer patients will present with advanced disease with a very poor overall survival. Although prior screening trials have shown no benefit from screening, there is renewed interest in low dose CT scanning as a screening modality for lung cancer. A high proportion of screen-detected cancers are early stage and resectable for cure. For the majority of these early stage patients, standard lobectomy is the treatment of choice. New options to potentially detect and treat early stage lung cancer will increase dramatically in the future.     

Radiation dose intensification in limited-stage small-cell lung cancer

Multiple studies have confirmed the value of radiation therapy in limited-stage small-cell lung cancer. The appropriate dose of radiation and the optimal fractionation scheme, however, remain controversial. This article will examine the history of radiation therapy in the management of small-cell lung cancer. It will review the rationale for the various approaches to radiation dose intensification, and review the results of important trials investigating the issue of radiation dose in the management of this disease. Survival outcomes and toxicity of various approaches to radiation dose intensification, including dose escalation and hyperfractionation, will be assessed. The implications of advancements in technology will be examined, and the optimal design of future trials will be discussed.