利用放射生物学模型比较周围型肺癌立体定向放射治疗中的3种剂量方案

目的:利用放射生物学模型比较周围型肺癌立体定向放射治疗（SBRT）中3种常见剂量方案3×15 Gy、4×12 Gy和3×18 Gy在肿瘤局部控制率（TCP）、放射性肺炎（RIP）、胸壁疼痛（CWP）和肋骨骨折（RIRF）发生概率方面的差异。方法:收集20例周围型早期肺癌的CT图像资料,分别采用3种剂量方案设计放射治疗计划,利用放射生物学模型计算每种剂量方案的TCP、RIP、CWP和RIRF概率值。结果:3种剂量方案对TCP没有显著影响;4×12 Gy剂量方案的放疗毒性最低,3×15 Gy放疗毒性稍有增高,而3×18 Gy的毒性最高;3×18 Gy剂量方案的RIP、CWP和RIRF发生概率均明显高于其它两种剂量方案。结论:3种剂量方案的TCP数值没有显著差别,4×12 Gy剂量方案的放疗毒性最低,3×18 Gy剂量方案显著增加RIP、CWP和RIRF的发生概率,建议临床治疗前应根据肿瘤与危及器官的毗邻关系选择合适的剂量方案,实施个体化治疗策略。     

High dose chemotherapy and peripheral blood stem cell transplantation for high risk primary breast cancer: a single center experience in Thailand

Twenty patients with high risk primary breast cancer underwent a high dose chemotherapy program at Ramathibodi Hospital, Bangkok. Eligible patients included 21 women who had a histological diagnosis of breast cancer with more than 10 axillary lymph nodes involved. The patients first underwent modified radical mastectomy, followed by conventional doxorubicin containing adjuvant chemotherapy, before entering the treatment program. Peripheral blood stem cells were mobilized with cyclophosphamide and G-CSF and were harvested by leukapheresis. High dose chemotherapy consisted of cyclophosphamide 5,625 mg/m2, cisplatinum 165 mg/m2 and carmustine (BCNU) 600 mg/m2 were subsequently given, followed by infusion of the harvested peripheral blood stem cells. The median duration of cytopenia after transplantation was 8 days (range 7-12). The median expense for the transplantation, in addition to the cost of mastectomy and conventional chemotherapy, was 224,396 Baht (approximately US $5,350). Three out of the first four patients developed interstitial pneumonitis within three months after transplantation. There was one fatal case which was the only regimen related mortality. BCNU was then reduced to 450 mg/m2 and lung complications were markedly reduced afterwards. The median follow up time was 37 months with a median disease free survival of 38 months and overall survival of four years at 84%.     

In search of a familial cancer risk assessment tool

Approximately one in three individuals will be affected by cancer in their lifetime in the United States, and some are at elevated risk because of family history. Although assessment of family history of cancer and cancer risk is the standard of care, the current health-care system appears unable to meet this need. Because individuals are increasingly using the Internet, web-based cancer risk assessment tools (CRATs) may provide a way to meet this need. The purpose of this review was to evaluate the types of familial CRATs available on the Internet and their nature. The current review evaluated five CRATs identified through an Internet search based on (i) their ability to identify those at the highest risk of cancer (i.e. those with hereditary cancer syndromes), (ii) their strengths and limitations based on criteria adapted from Rich and colleagues (2004, 2005), (iii) their readability based on four readability calculations, and (iv) their quality based on criteria from Health on the Net. The general limitations of CRATs as a whole were also delineated, including concerns about availability to those who are poor and underserved and those who have lower levels of literacy. Recommendations for future tools include assessing risk for a greater number of diseases, using theoretically driven approaches to increase the likelihood that individuals will engage in appropriate health behaviors, and making a greater effort to reach diverse populations.     

Referral for cancer genetics consultation: a review and compilation of risk assessment criteria

Methods: The criteria were based on a comprehensive review of publications describing diagnostic criteria for hereditary cancer syndromes and risk to first degree relatives of cancer patients. Priority was given to diagnostic criteria from consensus statements (for example, those from the National Comprehensive Cancer Network). Expert opinion from study personnel was then used to adopt a single set of criteria from other publications whenever guidelines differed.

Results: Based on family history, a set of criteria was developed to identify patients at risk for a hereditary cancer susceptibility syndrome, patients with moderate risk who might benefit from increased cancer surveillance, and patients who are at average risk. The criteria were applied to 4360 individuals who provided their cancer family history between July 1999 and April 2002, using a touch screen computer system in the lobby of a comprehensive cancer centre. They categorised an acceptable number of users into each risk level: 14.9% high risk, 13.7% moderate risk, and 59.6% average risk; 11.8% provided insufficient information for risk assessment.

Conclusions: These criteria should improve ease of referral and promote consistency across centres when evaluating patients for referral to cancer genetics specialists.

     

Psychosocial adjustment among pediatric cancer patients: a multidimensional assessment

Identified types and frequencies of psychological difficulties manifested by pediatric oncology patients and child-, family-, and illness-related correlates of adjustment. Parents of 48 children with cancer, 4 to 17 years of age, completed the Personality Inventory for Children (PIC). Analysis of mean PIC scores indicated that the children had a high frequency of somatic concerns and problems in academic functioning. Similar mean PIC profiles were obtained for children across gender, age, and diagnostic groups. Overall, 52% of the children had profiles with two or more clinically significant problem areas. Children's adjustment was associated with gender, social competence, and parental coping. Boys exhibited significantly more problems than did girls. Children whom teachers rated as less socially competent and whose parents reported few effective coping responses exhibited greater difficulties in adjustment.     

Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model

The development of accurate and clinically applicable tools to assess cancer risk is essential to define candidates to undergo screening for early-stage cancers at a curable stage or provide a novel method to monitor chemoprevention treatments. With the use of our recently developed optical technology--spatial-domain low-coherence quantitative phase microscopy (SL-QPM), we have derived a novel optical biomarker characterized by structure-derived optical path length (OPL) properties from the cell nucleus on the standard histology and cytology specimens, which quantifies the nano-structural alterations within the cell nucleus at the nanoscale sensitivity, referred to as nano-morphology marker. The aim of this study is to evaluate the feasibility of the nuclear nano-morphology marker from histologically normal cells, extracted directly from the standard histology specimens, to detect early-stage carcinogenesis, assess cancer risk, and monitor the effect of chemopreventive treatment. We used a well-established mouse model of spontaneous carcinogenesis--Apc(Min) mice, which develop multiple intestinal adenomas (Min) due to a germline mutation in the adenomatous polyposis coli (Apc) gene. We found that the nuclear nano-morphology marker quantified by OPL detects the development of carcinogenesis from histologically normal intestinal epithelial cells, even at an early pre-adenomatous stage (six weeks). It also exhibits a good temporal correlation with the small intestine that parallels the development of carcinogenesis and cancer risk. To further assess its ability to monitor the efficacy of chemopreventive agents, we used an established chemopreventive agent, sulindac. The nuclear nano-morphology marker is reversed toward normal after a prolonged treatment. Therefore, our proof-of-concept study establishes the feasibility of the SL-QPM derived nuclear nano-morphology marker OPL as a promising, simple and clinically applicable biomarker for cancer risk assessment and evaluation of chemopreventive treatment.     

Evaluation of risk assessment tools for suspected cancer in general practice: a cohort study

Background

Diagnostic delay is deemed to account for an estimated 5000 to 10 000 extra cancer deaths each year in the UK. Many cancer patients do not have symptoms meeting national referral criteria for rapid investigation. Risk assessment tools (RATs) have been developed to assist GPs in selecting patient for cancer investigation.

Aim

To assess the usability and acceptability of lung and colorectal RATs, as well as subsequent resource use and cancer diagnoses.

Design and setting

Cohort study with nested qualitative study with 614 GPs from 165 practices in seven English cancer networks were provided with RATs applicable to patients aged ≥40 years with bowel or respiratory symptoms. In-depth interviews were conducted with 34 individuals (11 project managers and 23 GPs).

Method

The study measured the number of RATs used, and subsequent cancer investigations and diagnoses, over a 6-month period and compared these with the previous 6 months.

Results

A total of 2593 RATs (1160 lung, 1433 colorectal) were completed. Compared with the preceding 6 months, there were 292 more chest X-rays, 104 extra 2-week chest clinic appointments, and 47 additional diagnoses of lung cancer. For suspected colorectal cancer, there were 304 more 2-week referrals, 270 more colonoscopies, and 10 more cancers identified. RATs appeared to help GPs in their selection of patients for cancer investigation. Users reported that RATs helped to confirm a need for investigation as well as allowing reassurance when investigation was not needed.

Conclusion

Use of RATs in primary care was accompanied by increased diagnostic activity and additional cancer diagnoses.     

Multigene panels in prostate cancer risk assessment: a systematic review

PurposeSingle-nucleotide polymorphism (SNP) panel tests have been proposed for use in the detection of, and prediction of risk for, prostate cancer and as prognostic indicator in affected men. A systematic review was undertaken to address three research questions to evaluate the analytic validity, clinical validity, clinical utility, and prognostic validity of SNP-based panels.MethodsData sources comprised MEDLINE, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and EMBASE; these were searched from inception to April 2013. The gray-literature searches included contact with manufacturers. Eligible studies included English-language studies evaluating commercially available SNP panels. Study selection and risk of bias assessment were undertaken by two independent reviewers.ResultsTwenty-one studies met eligibility criteria. All focused on clinical validity and evaluated 18 individual panels with 2 to 35 SNPs. All had poor discriminative ability (overall area under receiver-operator characteristic curves, 58–74%; incremental gain resulting from inclusion of SNP data, 2.5–11%) for predicting risk of prostate cancer and/or distinguishing between aggressive and asymptomatic/latent disease. The risk of bias of the studies, as assessed by the Newcastle Ottawa Scale (NOS) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tools, was moderate.ConclusionThe evidence on currently available SNP panels is insufficient to assess analytic validity, and at best the panels assessed would add a small and clinically unimportant improvement to factors such as age and family history in risk stratification (clinical validity). No evidence on the clinical utility of current panels is available.     

Variability of breast cancer risk in observational studies of hormone replacement therapy: a meta-regression analysis

OBJECTIVES: A re-analysis of data from 51 epidemiological studies reported a significant 14% increase in the risk of breast cancer associated with the use of hormone replacement therapy (HRT). Unlike randomized trials, these observational studies varied in design and methods. This study was conducted to explore the impact of study design factors on the rate ratio. METHODS: We performed a meta-regression analysis of 39 epidemiological studies of HRT and breast cancer. The rate ratio of breast cancer associated with ever use of HRT was evaluated in relation to study design, study period, country, primary study objective, method of exposure measurement, age control, adjustment factors related to reproduction and menopause, and the presence of breast cancer surveillance. We used stepwise multiple regression analysis, weighted by the inverse of the variance of the logarithm of the rate ratio, to estimate ratios of rate ratios for these factors. RESULTS: Exposure measured by personal interview and/or medical record review was associated with a 14% lower rate ratio estimate as compared with telephone interview or self-administered questionnaire (P = 0.018). Among studies that did not adjust for age at menopause, the rate ratio was 12% lower if the primary objective was HRT effect than not (P = 0.016), while it was 43% higher among studies that adjusted for age at menopause (P = 0.042). An index that included as six desirable design features, breast cancer surveillance, matching of controls, more reliable exposure information, adjustment for age at menopause and reproductive risk factors, and as primary objective the effect of HRT suggests that studies with none of these properties would lead to a rate ratio estimate of 1.14 (95% CI: 1.00-1.29) while studies with all six properties would produce a rate ratio of 0.98 (95% CI: 0.83-1.15). CONCLUSIONS: Design factors of epidemiological studies could be an alternative explanation for the reported 14% increase in the risk of breast cancer associated with the use of HRT.     

Efficacy of a touchscreen computer based family cancer history questionnaire and subsequent cancer risk assessment

OBJECTIVE—A computer based touchscreen family cancer history questionnaire was developed and implemented to facilitate the provision of cancer risk assessments for the ambulatory and outpatient populations of a free standing cancer hospital.
METHODS—A questionnaire consisting of a series of branched point decision making screens was developed which enables the participant to enter demographic data, personal cancer history, and cancer histories for first and second degree relatives. A freestanding touchscreen computer kiosk system was used to place the questionnaire in public areas of the cancer hospital and clinic. Genetic professionals analysed the data received, using published criteria, and provided a basic cancer risk assessment and surveillance recommendations within 10 business days. A survey was completed by a small random group of users (n=59) three to six months after receipt of their risk assessment.
RESULTS—After 11 months, 1440 people had entered information and received a written communication. Only 2% of completed questionnaires contained insufficient information to provide a basic risk assessment. Of the small group of participants surveyed, almost all (95%) felt "very comfortable" using the system, 93% remembered receiving the risk assessment letter when queried three to six months later, 42% felt their perceptions about cancer risk had changed, and 20% had made changes in their or their family's cancer surveillance practices.
CONCLUSION—The touchscreen computer family history questionnaire allows easy collection of family history information, provision of risk assessments to a broad population, and promotes increased awareness of familial risk and appropriate surveillance.


Keywords: genetic counselling; risk assessment; computers; medical informatics     

Genetic and environmental risk assessment for colorectal cancer risk in primary care practice settings: a pilot study.

PURPOSE: The assessment of genetic variants and environmental exposures (i.e., genetic and environmental risk assessment) may permit individualized risk stratification for common diseases as part of routine care. A pilot study was conducted to assess the uptake of, and response to, testing for colorectal cancer risk among average risk patients in primary care practice settings. METHODS: Physicians in primary care practices identified patients eligible for colorectal cancer screening and referred them to the study. Research staff administered a baseline survey to consenting patients. At a scheduled office visit, participants underwent decision counseling with a trained nurse educator to facilitate informed decision making about being tested for methylene tetrahydrofolate reductase status and red blood cell folate level. Combined assessment can stratify colorectal cancer risk. Test results were disclosed within 2 weeks after the visit. Postvisit and 1-month endpoint surveys were administered. Univariable analyses of survey data were performed to assess changes from baseline in genetic and environmental risk assessment and colorectal cancer screening-related knowledge and perceptions. RESULTS: Of the 57 patients who were referred to the study, 25 (44%) consented to participate, and all but one were tested. Participant knowledge about genetic and environmental risk assessment and colorectal cancer screening, perceived colorectal cancer screening response efficacy, and perceived social support for colorectal cancer screening increased significantly from baseline. Participants reported low levels of intrusive thoughts about CRC. CONCLUSION: Knowledge and favorable perceptions of colorectal cancer screening increased, as did knowledge about genetic and environmental risk assessment, after exposure to the study intervention. Further research is needed to assess genetic and environmental risk assessment uptake and impact at the population level.     

Atypia in the assessment of breast cancer risk: implications for management

Proliferative disease accounts for as much as one-third of all biopsies for benign disease and 5-10% of proliferative lesions show atypia ductal or lobular hyperplasia. Nearly 40% of women with a family history of breast cancer and atypical hyperplasia subsequently develop breast cancer. A quantitative model developed by Gail and colleagues estimates the probability of developing breast cancer over time. Risk factors in the model include current age, ages at menarche and first live birth, number of previous biopsies, the presence of cellular atypia, and the number of first-degree relatives with breast cancer. Atypical hyperplasia approximately doubles the risk of developing invasive breast cancer within any quantitative risk profile. Ductal lavage provides a minimally invasive method of collecting breast epithelial cells. The procedure opens the possibility of repeatable tracking of breast cytology over time, but its role as a risk assessment tool remains to be fully defined.     

Studies of dose distribution, premutagenic events and mutation frequencies for benzo[a]pyrene aiming at low dose cancer risk estimation.

Cancer risk assessment of polycyclic aromatic hydrocarbons (PAH) is complicated by several of these compounds exerting a promoter action leading to high tumour incidences at high doses. Cancer risks at low doses corresponding to the uptake from air and food in the general environment would best be estimated on the basis of measurement of in vivo target doses of genotoxic (mutagenic) intermediates and a determination of mutation frequency per unit of dose. In experiments ultimately aiming at a risk assessment of environmental PAH from in vivo doses benzo[a]pyrene (BaP) was chosen as a model. gamma-Radiation has earlier been used as a reference standard in cancer risk estimation of genotoxic chemicals where dose equivalents (rad-equivalents) have been shown to give reliable risk estimates for several alkylating agents. Variation in dose of BaP diolepoxide between organs was studied by measurement of deoxyguanosine-N(2) adducts in DNA after administration of BaP by gavage to mice of a strain with reduced DNA repair (Xpa(-/-)). The adduct levels in spleen, forestomach, stomach and small intestine were approximately the same; with the adduct level in spleen as reference it was twice as high in liver and lung and about half as high in colon tissue. A chemical or radiation dose is proportional to the cumulative frequency of putatively premutagenic changes (premutagenic hits) in DNA. The mutation frequency per premutagenic hit (genotoxic chemicals) and per unit of dose (gamma-radiation) were calculated from acutely exposed V79 cells in order to determine the mutagenic effectiveness of each agent. Based on the mutagenic effectiveness determined in this study 10(-4) Gy can be regarded equally effective in causing phenotypically expressed HPRT mutations as the dose of BaP which causes the formation of one deoxyguanosine-N(2) adduct per cell.     

周围型肺癌立体定向放射治疗中采用实体肿瘤靶区推量技术的可行性研究——基于剂量学分析

目的：通过研究周围型肺癌立体定向放射治疗中提高肿瘤靶区最高剂量对剂量限制参数和正常器官剂量的影响,探讨使用实体肿瘤靶区推量技术的可行性,为临床治疗提供剂量学参考依据。方法：收集19例周围型早期肺癌患者的CT图像资料,重新设计放射治疗计划,初始治疗计划在满足放射治疗肿瘤协作组（RTOG）0915号报告关于剂量限制参数的情况下,以2 Gy的剂量爬升梯度分别对肿瘤靶区进行提量,共得到5组治疗计划。结果：5组计划的剂量限制参数均能满足RTOG0915号报告要求。5组计划的剂量限制参数和正常器官剂量无显著差异,但是肿瘤靶区最高剂量存在显著差异（P<0.05）,最高和最低剂量组剂量差异可达6.6 Gy。结论：提高肿瘤靶区最高剂量对剂量限制参数和正常器官剂量没有显著影响。由于提高靶区内最高剂量会直接影响肿瘤的局部控制率,因此在满足剂量限制参数的前提下,建议使用实体肿瘤靶区推量技术以提高肿瘤靶区内的最高剂量。