Conundrums in screening for cancer

Screening for cancer has to be carefully organized for maximum effectiveness, and introduced in full understanding of the natural history of the disease. There are major potential harms as well as benefits from screening. The current state of art for breast, cervix and prostate cancer screening is reviewed, only for breast and cervix are policies of screening in the population justified.     

Screening for colorectal cancer

This review will comprise a general overview of colorectal cancer (CRC) screening. We will cover the impact of CRC, CRC risk factors, screening modalities, and guideline recommendations for screening in average-risk and high-risk individuals. Based on this data, we will summarize our approach to CRC screening.     

Screening for cancer: future potential

Much progress has been made in cancer screening over the past decade, but a great deal more needs to be done if screening is to make a major impact on worldwide cancer mortality. Where fully implemented, cytological screening for cervical precursor lesions has had a major impact on mortality. However, the cost and required infrastructure levels are high, and new approaches are needed if screening is to be effective in the developing world. Testing for the human papillomavirus and automated liquid based cytology offer great promise to improve quality, reduce overall cost and make screening more viable generally. Breast screening has been less successful, although useful mortality benefits have been achieved in women aged over 50 years. Full implementation in countries that can afford it will save lives, but radical new approaches will be needed to conquer breast cancer. Colorectal cancer screening offers the best hope of a major reduction in cancer mortality over the next decade. Less certainty exists about screening for other major cancers such as lung, prostate and ovary, but a range of potential approaches merit investigation. ©     

Dideoxy fingerprinting assay for BRCA1 mutation analysis

Since the isolation of BRCA1, the familial breast/ovarian cancer predisposition gene, much effort has been invested in characterizing the mutation spectrum. The large size of the gene and the wide distribution of its more than 100 mutations has increased the challenge of this endeavor such that traditional mutation detection techniques are inadequate. We examined the sensitivity of dideoxy fingerprinting (DDF), which combine a Sanger sequencing reaction with multiple-fragment single-strand conformation analysis (SSCA), as a mutation detection technique to screen BRCA1. Here we describe the technique and compare its sensitivity with that of SSCA in detecting 21 previously described BRCA1 sequence variants. All the variants were detected by DDF, but only 17 of 21 (81%) were observed by SSCA under standard conditions. Three of four alterations missed by SSCA were base substitutions. As a BRCA1 mutation detection technique, DDF was more sensitive than SSCA and may prove to be a useful research tool in defining the mutation spectrum within this and other genes. Mol. Carcinog. 19:176–179, 1997. © 1997 Wiley-Liss, Inc.     

Cost considerations for systemic therapy for patients with advanced genitourinary malignancies

The rising cost of health care in the United States has been the focus of intense debate within the medical, legal, and legislative arenas, with the cost of cancer care representing an important component. Cost effectiveness is not always easy to define, and there is no standard metric in assessing this measure related to cancer therapies. Significant controversy surrounds exactly what is the appropriate cost per added year of life. This review examines cost, effectiveness, and comparative cost effectiveness of novel systemic therapies for patients with urologic malignancies. Cancer 2018;124:2897‐905. © 2018 American Cancer Society.     

甲状腺癌术后残留和复发病灶的放射治疗

目的 :分析甲状腺术后残余癌的预后因素及探讨放疗的价值 (包括术后复发 18例 )。材料与方法 :196 5年 1月～ 1987年 12月间对 10 9例 (包括术后复发 18例 )甲状腺术后残余癌患者全部行放射治疗。结果 :其 5 ,10 ,15 ,2 0 ,2 5年生存率分别为 93.6 %、91.7%、88.7%、87.6 %、87.6 % ;无瘤生存率分别为 90 .8%、89.8%、85 .6 %、84 .1%、84 .1%。影响预后因素分析结果显示 :肿瘤的临床分期是影响生存率的决定性因素。年龄、性别、组织学类型、、放射剂量均影响预后。结论 :甲状腺癌术后如有残留需补充放疗 ,不但能增加局部肿瘤的控制率且能提高生存率。最佳剂量为 4 5～ 6 5 Gy。     

Radiotherapy for primary thyroid cancer as a risk factor for second primary cancers

Although radiation is considered a risk factor for thyroid cancer, the potential relationship between radiation therapy and the risk of second primary cancer among patients with first primary thyroid cancer has not been evaluated. We identified 26,639 patients with first primary thyroid cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2000. Information on radiation therapy as well as second primary cancers was recorded in SEER. The proportional hazards model was utilized to estimate adjusted risk ratios (RRs) and their 95% confidence intervals (CIs) to assess the potential association between radiation therapy for thyroid cancer and the risk of second primary cancers. With 270,674.33 person-years of follow-up, 1,896 (7.1%) of the 26,639 patients with first primary thyroid cancer developed second primary cancers. Among the second primaries, 35 occurred in the thyroid. No obvious association was observed between radiation therapy and the overall risk of second primary cancer after ten years of follow-up (RR=1.07, 95% CI=0.88-1.30). However, an increased risk was seen for several cancers, including upper digestive system cancers (RR=1.66, 95% CI=1.07-2.57) and myeloid malignancies (RR=3.26, 95% CI=1.39-7.67). Radiation therapy was associated with reduced second cancer risks for thyroid cancer (RR=0.18, 95% CI=0.04-0.76). Beam radiation might be important to the digestive system, radioactive implants might be associated with the male genital system, radioisotopes might have an effect on myeloid malignancies, and combined beam radiation with radioactive implants or radioisotopes might be related to the increased risk of respiratory system cancers. This study suggests that radiation therapy for patients with first primary thyroid cancer might be associated with an increased risk of developing a second primary cancer in the upper digestive system and second primary myeloid malignancies. Radiation therapy for adult patients with thyroid cancer might be associated with a reduced risk of second primary thyroid cancer.     

Cancer statistics for adolescents and young adults, 2020

Cancer statistics for adolescents and young adults (AYAs) (aged 15-39 years) are often presented in aggregate, masking important heterogeneity. The authors analyzed population-based cancer incidence and mortality for AYAs in the United States by age group (ages 15-19, 20-29, and 30-39 years), sex, and race/ethnicity. In 2020, there will be approximately 89,500 new cancer cases and 9270 cancer deaths in AYAs. Overall cancer incidence increased in all AYA age groups during the most recent decade (2007-2016), largely driven by thyroid cancer, which rose by approximately 3% annually among those aged 20 to 39 years and 4% among those aged 15 to 19 years. Incidence also increased in most age groups for several cancers linked to obesity, including kidney (3% annually across all age groups), uterine corpus (3% in the group aged 20-39 years), and colorectum (0.9%-1.5% in the group aged 20-39 years). Rates declined dramatically for melanoma in the group aged 15 to 29 years (4%-6% annually) but remained stable among those aged 30 to 39 years. Overall cancer mortality declined during 2008 through 2017 by 1% annually across age and sex groups, except for women aged 30 to 39 years, among whom rates were stable because of a flattening of declines in female breast cancer. Rates increased for cancers of the colorectum and uterine corpus in the group aged 30 to 39 years, mirroring incidence trends. Five-year relative survival in AYAs is similar across age groups for all cancers combined (range, 83%-86%) but varies widely for some cancers, such as acute lymphocytic leukemia (74% in the group aged 15-19 years vs 51% in the group aged 30-39 years) and brain tumors (77% vs 66%), reflecting differences in histologic subtype distribution and treatment. Progress in reducing cancer morbidity and mortality among AYAs could be addressed through more equitable access to health care, increasing clinical trial enrollment, expanding research, and greater alertness among clinicians and patients for early symptoms and signs of cancer. Further progress could be accelerated with increased disaggregation by age in research on surveillance, etiology, basic biology, and survivorship.     

阿帕替尼在实体肿瘤治疗中的应用与研究进展

血管生成在细胞生长的过程中具有重要作用,同时也是肿瘤发生的基础。因此,抑制肿瘤血管生成是抗肿瘤的有效途径。阿帕替尼是一种新型小分子抗血管生成抑制剂,通过特异性抑制血管内皮细胞生成因子-2（VEGFR-2）的酪氨酸激酶活性,从而达到抑制肿瘤血管生成,发挥抗肿瘤作用。阿帕替尼最初在胃癌治疗中取得成效,随后在乳腺癌、肺癌、肝癌以及软组织等肿瘤中亦发现了其应用前景。本文将阿帕替尼在多种实体肿瘤中的相关临床试验进行综述,使读者更加全面地认识阿帕替尼,为临床实践提供参考,并期望为恶性肿瘤患者的治疗带来一些新的选择。     

Trends in in-patient Hospital Utilization and Surgical Procedures for Breast,Prostate, Lung and Colorectal Cancers in Canada

Objective: To analyse population-based trends of in-patient surgical procedures for breast (female), prostate, lung and colorectal cancers. Methods: The Hospital Morbidity Files supplied hospital data and the Canadian Cancer Registry, incidence data. Age-adjusted rates were standardized to the 1991 Canadian population. Results: All four cancers showed major changes in trends of surgical procedures. For breast cancer, the rate of in-patient breast conservation surgery (BCS) increased from 1981 to the early 1990s while the rate of mastectomy decreased. Because day surgery was not included, the subsequent in-patient BCS rate stayed level. For prostate cancer, the rate of transurethral prostatectomy was initially high but decreased after 1990, while the rate of radical prostatectomy increased rapidly, only minimally affected by the PSA-related peak in incidence. The lung cancer lobectomy rate in men remained at 10/100,000 after 1986, but in women rose from 3/100,000 to 7/100,000, reflecting increasing lung cancer incidence. For colorectal cancer, right hemicolectomies and anterior resections increased, especially in men. Conclusions: Surgery trends reflected changes in incidence and treatment preferences. Canadian trends were generally similar to US trends, although the timing of some of the changes differed. Canadians tended to use less invasive procedures such as BCS and anterior resection.     

Laboratory and clinical basis for hyperthermia as a component of intracavitary chemotherapy

Intraoperative chemotherapy with heat has been identified as a treatment option for patients with cancer spread to peritoneal surfaces. This treatment modality is viewed as a supplement to several other treatments for this group of patients including cytoreductive surgery, systemic chemotherapy, early postoperative intraperitoneal chemotherapy, and long-term bidirectional chemotherapy. The pharmacologic basis for using heat to supplement chemotherapy effects are related to the increased penetration of chemotherapy into tumor with hyperthermia, the delayed clearance of chemotherapy from the peritoneal cavity after direct instillation, and an increased cytotoxicity that has been documented with selected chemotherapy agents. Data to support the use of perioperative hyperthermic intraperitoneal chemotherapy with mucinous appendiceal carcinomatosis comes from a large number of single institution phase II studies. Also, peritoneal and pleural mesothelioma are benefited. In colon cancer carcinomatosis, large phase II multi-institutional trials and a single phase III trial documented an increased median survival of these patients from approximately 1 year to over 2 years. Prophylaxis against peritoneal carcinomatosis in gastric cancer has been demonstrated in phase III trials. In ovarian cancer the rationale for this treatment remains large but its current application is limited. Much work needs to be done to identify a proper clinical perspective on hyperthermia used with chemotherapy in patients with peritoneal surface malignancy.     

Blueprint for cancer research: Critical gaps and opportunities

We are experiencing a revolution in cancer. Advances in screening, targeted and immune therapies, big data, computational methodologies, and significant new knowledge of cancer biology are transforming the ways in which we prevent, detect, diagnose, treat, and survive cancer. These advances are enabling durable progress in the goal to achieve personalized cancer care. Despite these gains, more work is needed to develop better tools and strategies to limit cancer as a major health concern. One persistent gap is the inconsistent coordination among researchers and caregivers to implement evidence-based programs that rely on a fuller understanding of the molecular, cellular, and systems biology mechanisms underpinning different types of cancer. Here, the authors integrate conversations with over 90 leading cancer experts to highlight current challenges, encourage a robust and diverse national research portfolio, and capture timely opportunities to advance evidence-based approaches for all patients with cancer and for all communities.     

Loco-regional recurrences after mastectomy in breast cancer: prognostic factors and implications for postoperative irradiation

Purpose: Potential risk factors including DNA flow cytometric-derived parameters predicting loco-regional recurrence (LRR) in early breast cancer were investigated.

Materials and methods: This study included 608 patients treated by modified radical mastectomy between 1982 and 1987. Recommendations regarding local treatment as well as adjuvant systemic therapy did not change during this period. Patients treated by adjuvant chemotherapy were randomized to receive additional medroxyprogesterone acetate (MPA) treatment. Only 59 (10%) patients received postoperative irradiation (XRT) to the chest wall and/or axillary lymph nodes; another 121 (20%) patients received XRT to the internal mammary nodes because of centromedially located tumours.

Results: Patients were followed for a median period of 7.5 years. The event-free survival at 10 years was 50%. The cumulative incidence rate of LRR at 10 years was 18% (n=93), either with (n=30) or without (n=63) concurrent distant metastases. The chest wall, regional lymph nodes or both were involved in 41 (44%), 38 (41%) and 12 (13%) patients, respectively. Multivariate analysis according to the Cox model revealed two factors associated with LRR, i.e. pT (P<0.05) and nodal status (P<0.05). In node-positive patients extracapsular tumour extension (ECE) and pT were independent risk factors. DNA ploidy and S-phase fraction did not yield additional information. Based on pT, nodal status and extracapsular extension of tumour growth a high risk (>10%) and low risk (<10%) group for LRR could be identified.

Conclusions: Results indicate that T-stage and nodal status, combined with ECE, may help to identify patients at risk for loco-regional recurrence, whereas DNA flow cytometry does not.     

Familial risk for gastric carcinoma: an updated study from Sweden

Reliable data on familial risks are important for clinical counselling and cancer genetics. However, the estimates of familial risk of gastric cancer vary widely. We examined the risk of familial gastric cancer using the updated Swedish Family-Cancer Database with 5358 patients among offspring and 36,486 patients among parents. There were 133 families with one parent and one offspring diagnosed with gastric cancer, and 20 families with two affected offspring. Familial standardised incidence ratios (SIRs) were 1.63 and 2.93 when parents and siblings presented with gastric cancer, respectively. The high sibling risk was owing to cancer in the corpus (SIR 7.28). The SIR for cardia cancer was 1.54 when parents were diagnosed with any gastric cancer. Cardia cancer associated with oesophageal cancer, particularly with oesophageal adenocarcinoma. Among specific histologies, signet ring cancer showed an increase. A few associations were noted for discordant sites, including the urinary bladder and the endometrium. H. pylori infection, although not measured in the present study, is probably an important risk factor for the high sibling risk of corpus cancer. Familial clustering of cardia cancer is independent of H. pylori infection, and may have a genetic basis. The familial association of cardia cancer with oesophageal adenocarcinoma may provide aetiological clues.     

5-Year Survival Rates for Primary Cancer Sites at Cancer-Treatment-Oriented Hospitals

In Japan, The Japanese Association of Clinical Cancer Centers (JACCCs) was established in 1965 by systematizing ‍cancer-treatment-oriented hospitals. The core center of JACCCs is the National Cancer Center in Tokyo. In 1984, ‍JACCCs created The “Improvement for Clinical Cancer Centers in Japan” Study Group (The Study Group) which ‍has subsequently routinely evaluated the effectiveness of the therapy that is provided. In general, the 5-year (relative) ‍survival rate is employed as an indicator of the treatment efficacy. The present survey used the PC software program ‍KAP developed by Chiba Cancer Center in Japan, to calculate 5-year observed survival rates and the 5-year relative ‍survival rates using Ederer II methods. The overall 5-year relative survival rates in patients with stomach (15,353 ‍patients), colon (5,054), rectum (3,695), lung (10,153), breast (11,302) and cervix of the uterus (6,336) were 68.7%, ‍72.2%, 69.4%, 28.1%, 86.1% and 81.1%, respectively. The survival rates discussed so far are principally observed ‍survival rates. The 5-year relative survival rate for those institutions that specialize in cancer treatment should ‍become an index for Japanese cancer treatment.     

A Registry Program for Familial Gastric Cancer Patients Referred to Cancer Institute of Iran

Background: Gastric cancer is the second most common cause of cancer death. It has a poor prognosis withonly 5-10% of hereditary etiology. If it is diagnosed, it could be helpful for screening the other susceptible membersof a family for preventive procedures. Usually it is identified by symptoms such as presence of cancer in differentmembers of family, some special type of pathology such as diffused adenocarcinoma, having younger age andmultiple cancer syndromes. Hence, designing a registry program can be a more practical way to screen highrisk families for a preventive program. Materials and Methods: Based on the inclusion criteria, a questionnairewas prepared. After pilot on a small number of patients, the actual data was collected from 197 patients andprocessed in SPSS 16.0. Results: Totally, 11.8% of the patients were younger than 45 years old. Blood type ‘A’ wasdominant and males had a higher risk behavior with higher consumption of unhealthy food. Adenocarcinomawas reported in majority of cases. 21.8% of the patients had the including criteria for familial gastric cancer(FGC). Conclusions: The high percentage of FGC population compared to the other studies have revealed a needto design an infrastructural diagnostic protocol and screening program for patients with FGC, plus preventiveprogram for family members at risk which could be done by a precise survey related to frequency and foundermutations of FGC in a national registry program.