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PubMed2000

Harvard report on cancer prevention volume 4: Harvard Cancer Risk Index. Risk Index Working Group, Harvard Center for Cancer Prevention.

OBJECTIVE: Prediction of cancer risk is a minor component of current health risk appraisals. Perception of individual cancer risk is poor. A Cancer Risk Index was developed to predict individual cancer risk for cancers accounting for 80% of the cancer burden in the United States. METHODS: We used group consensus among researchers at the Harvard Medical School and Harvard School of Public Health to identify risk factors as definite, probable and possible causes of cancer. Risk points were allocated according to the strength of the causal association and summed. Population average risk of cancer and cumulative 10-year risk was obtained from SEER data. Individual ranking relative to the population average was determined. The risk index was evaluated for validity using colon cancer incidence in prospective cohort data. RESULTS: The Harvard Cancer Risk Index provides a broad classification of cancer risk. Validation against cohort data shows good agreement for colon cancer. CONCLUSION: The Harvard Cancer Risk Index offers a simple estimation of personal risk of cancer. It may help inform users of the major risk factors for cancer and identify changes in lifestyle that will reduce their risk. It offers the potential for tailored health-promotion messages.

Adult↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed1999

The relationship of rural persons' multidimensional health locus of control to knowledge of cancer, cancer myths, and cancer danger signs.

The purpose of the study was to determine if a relationship exists between multidimensional health locus of control and knowledge of breast cancer, prostate cancer, cancer myths, and danger signs. A descriptive correlational design was used. A convenience sample of 78 rural men and 79 rural women participated in the study. Participants completed three questionnaires: (a) the Cancer Danger Signs Questionnaire, (b) the Cancer Myths Questionnaire, (c) the Prostate Cancer Knowledge Test (completed by the men) and the Breast Cancer Knowledge Test (completed by the women). Results indicated that an internal score on the Multidimensional Health Locus of Control (MHLOC) scale did not predict knowledge of breast cancer in women, prostate cancer in men, cancer myths, or danger signs. Women who scored high on the Powerful Others subscale of the MHLOC had statistically significant high scores on knowledge of breast cancer, but not on cancer myths and danger signs. The MHLOC and its subscales did not predict knowledge of prostate cancer, cancer myths, or cancer danger signs for the male participants. The implications of these results for rural nursing practice and their relationship to previous research are discussed.

Adult↗

PubMed1991

[A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers].

A late phase II study of CPT-11, a new derivative of camptothecin, in uterine cervical cancer and ovarian cancer was carried out by a cooperative study group at 26 institutions. Out of 144 patients enrolled, total cases were 110, involving 55 uterine cervical cancers and 55 ovarian cancers. In uterine cervical cancer, 5 cases of complete response (CR) and 8 cases of partial response (PR) were observed, with a response rate of 23.6% and a CR rate of 9.1%. In ovarian cancer, 13 cases of PR were observed, response rate was 23.6%. Both in uterine cervical cancer and ovarian cancer, the 95% confidence interval of response rate was 12.4-34.8%. In cases having undergone previous chemotherapy including platinum, derivatives, the response rate in ovarian cancer was 23.1% (12/52). In cases of uterine cervical cancer having previous radiotherapy, the response rate was 26.8% (11/41). In ovarian cancer of various histological types, a response was observed for not only serous cystadenocarcinoma but also mucinous cystadenocarcinoma, etc. A response was observed in distant metastatic lesions such as lung metastasis as well as primary lesion in uterine cervical cancer and ovarian cancer. Major adverse reactions were leukopenia, nausea and vomiting, diarrhea and anorexia, and these incidences (grade 2 or more) were 87.3, 60.3, 44.0 and 67.2%, respectively. Since some patients experienced severe adverse reactions, caution should be taken in treatment with CPT-11. Besides these reactions, alopecia was observed (33.1%), but severe adverse reactions such as nephropathy were not found. No significant difference in the efficacy and adverse reactions were observed between administration methods; A, 100 mg/m2 once weekly and B, 150 mg/m2 once every 2 weeks. Both were thought to be clinically useful. These results suggest that CPT-11 is clinically effective against uterine cervical cancer and ovarian cancer.

Adult↗

PubMed1995

Public education projects in skin cancer. The evolution of skin cancer prevention education for children at a comprehensive cancer center.

BACKGROUND: Skin cancer affects more Americans than any other type of cancer. Children are prime targets for prevention education, because sun overexposure in early childhood may affect the development of skin cancer later in life. Preventive behaviors adopted early in life may be less resistant to change than those acquired in adulthood. Thus, there is a need to educate children at an early age about sun overexposure. METHODS: This article describes the evolution of skin cancer prevention research at the Arizona Cancer Center, a National Cancer Institute--designated comprehensive cancer center. Research focusing on children is high-lighted. RESULTS: From its roots in the Arizona Sun Awareness Project, an informal public skin cancer education program, skin cancer prevention research at the Arizona Cancer Center has produced two developmentally appropriate, age-based curricula aimed at teaching children about the benefits and dangers of the sun. The elementary school curriculum, Sunny Days, Healthy Ways, has undergone two tests of feasibility and is the intervention used in a large, randomized, experimental trial. The preschool curriculum, Be Sun Safe, has been tested in a randomized trial and was found to have a positive effect on preschoolers' knowledge and comprehension of sun safety. CONCLUSIONS: Educating children about skin cancer may be an important way of decreasing the incidence of skin cancer. Although informal skin cancer prevention education can be helpful, educational programs preferably should be research based and evaluated for effectiveness before public distribution. The Arizona Cancer Center experience can serve as a model for other programs.

Adolescent↗

PubMed2003

Expression of aphidicolin-induced fragile sites and their relationship between genetic susceptibility in breast cancer, ovarian cancer, and non-small-cell lung cancer patients.

Fragile sites are nonrandomly located gaps and/or breaks and their expres-sion can be induced by specific culture conditions. There are many reports in the literature that indicate that these sites can act as factors that predispose to specific chromosome aberrations and other complex rearrangement in the chromosome and their association with cancers. In the present study, the expression of the fragile sites induced by aphidicolin was evaluated on prometaphase chromosomes from peripheral blood lymphocytes of 55 patients with breast cancer patients belonging to different stages of the cancer, 25 patients with epithelial ovarian cancer, and 13 with non-small-cell lung cancer, 100 of their first-degree clinically healthy female relatives, and 100 normal age-matched healthy persons without a familial history of cancer. The frequency of expression of the fragile sites in cancer patients and their first-degree relatives was found to be statistically significant (P<0.05) than those of the controls. In different stages of breast cancer patients, 6q26 is the best-defined fragile site whereas 13q13 is confined to stage II and stage III patients only. The chromosomal aberration rate/cell in breast cancer patients was found to be 0.29+/-0.13, in epithelial ovarian cancer patients 0.38+/-0.14, and in non-small-cell lung cancer 0.29+/-0.11 as compared to 0.07+/-0.03 in controls, and was found to be statistically significant. Therefore, our results indicate that these fragile sites may be the unstable sites in the genome and, hence, can be used as suitable and reliable markers for genetic predisposition to breast cancer, epithelial ovarian cancer, and in non-small-cell lung cancer.

Aphidicolin↗

PubMed2007

A meta-analysis of second cancers after a diagnosis of nonmelanoma skin cancer: additional evidence that solar ultraviolet-B irradiance reduces the risk of internal cancers.

BACKGROUND: Nearly 20 types of cancer have been found to be inversely correlated with solar ultraviolet-B (UVB) levels determined geographically in ecologic studies, assuming that personal solar UVB irradiances were directly related to July solar UVB doses. This assumption has been questioned. METHODS: Rates of second cancer after diagnosis of nonmelanoma skin cancer (NMSC) from the literature were used in linear regression analyses. The risk modification of NMSC due to smoking was accounted for by comparing second cancer risk ratios (RRs) with lung cancer RRs in regression analysis for each cancer. RESULTS: For a diagnosis of squamous cell carcinoma, RRs for subsequent colon, gastric, and rectal cancers were significantly reduced, with that for renal cancer being marginally insignificant. For NMSC, RRs for cervical, esophageal, gastric, and rectal cancer were significantly reduced; those for colon and gallbladder cancer were marginally insignificant, while those for female breast, laryngeal, ovarian, renal, and uterine corpus cancers were insignificantly reduced; RRs for lip and salivary gland cancers and melanoma were significantly increased. Melanoma was inversely correlated with lung cancer. CONCLUSION: These results provide nearly direct evidence that solar UVB irradiance reduces the risk of many internal cancers. The likely mechanism is production of Vitamin D.

Female↗

PubMed1998

Risk of cancer among offspring of childhood-cancer survivors. Association of the Nordic Cancer Registries and the Nordic Society of Paediatric Haematology and Oncology.

BACKGROUND: Increasing numbers of children with cancer survive and reach reproductive age. However, the risk of cancer (other than retinoblastoma) in the offspring of survivors of childhood and adolescent cancer is uncertain. METHODS: Using data from national cancer and birth registries, we assessed the risk of cancer among 5847 offspring of 14,652 survivors of cancer in childhood or adolescence diagnosed since the 1940s and 1950s in Denmark, Finland, Iceland, Norway, and Sweden. The offspring were followed up for a diagnosis of cancer for 86,780 person-years, and standardized incidence ratios were calculated. RESULTS: Among the 5847 offspring, 44 malignant neoplasms were diagnosed (standardized incidence ratio, 2.6; 95 percent confidence interval, 1.9 to 3.5). There were 17 retinoblastomas, yielding a standardized incidence ratio of 37. There were 27 neoplasms other than retinoblastoma (standardized incidence ratio, 1.6; 95 percent confidence interval, 1.1 to 2.4). The second most common primary site of cancer among the offspring was the brain and nervous system, in which eight tumors were observed (standardized incidence ratio, 2.0; 95 percent confidence interval, 0.9 to 3.9.) There were between zero and four apparently sporadic cases of cancer in other primary sites among the offspring. Excluding 4 likely cases of hereditary cancer and 2 subsequent cancers among the offspring with hereditary retinoblastoma, there were 22 sporadic cancers, for a standardized incidence ratio of 1.3 (95 percent confidence interval, 0.8 to 2.0). CONCLUSIONS: There is no evidence of a significantly increased risk of nonhereditary cancer among the offspring of survivors of cancer in childhood.

Adolescent↗

PubMed2002

Methodology to predict long-term cancer survival from short-term data using Tobacco Cancer Risk and Absolute Cancer Cure models.

Three parametric statistical models have been fully validated for cancer of the larynx for the prediction of long-term 15, 20 and 25 year cancer-specific survival fractions when short-term follow-up data was available for just 1-2 years after the end of treatment of the last patient. In all groups of cases the treatment period was only 5 years. Three disease stage groups were studied, T1N0, T2N0 and T3N0. The models are the Standard Lognormal (SLN) first proposed by Boag (1949 J. R. Stat. Soc. Series B 11 15-53) but only ever fully validated for cancer of the cervix, Mould and Boag (1975 Br. J. Cancer 32 529-50), and two new models which have been termed Tobacco Cancer Risk (TCR) and Absolute Cancer Cure (ACC). In each, the frequency distribution of survival times of defined groups of cancer deaths is lognormally distributed: larynx only (SLN), larynx and lung (TCR) and all cancers (ACC). All models each have three unknown parameters but it was possible to estimate a value for the lognormal parameter S a priori. By reduction to two unknown parameters the model stability has been improved. The material used to validate the methodology consisted of case histories of 965 patients, all treated during the period 1944-1968 by Dr Manuel Lederman of the Royal Marsden Hospital, London, with follow-up to 1988. This provided a follow-up range of 20-44 years and enabled predicted long-term survival fractions to be compared with the actual survival fractions, calculated by the Kaplan and Meier (1958 J. Am. Stat. Assoc. 53 457-82) method. The TCR and ACC models are better than the SLN model and for a maximum short-term follow-up of 6 years, the 20 and 25 year survival fractions could be predicted. Therefore the numbers of follow-up years saved are respectively 14 years and 19 years. Clinical trial results using the TCR and ACC models can thus be analysed much earlier than currently possible. Absolute cure from cancer was also studied, using not only the prediction models which incorporate a parameter for a statistically cured fraction of patients C(SLN), C(TCR) and C(ACC), but because of the long follow-up range of 20-44 years, also by complete life analysis. The survival experience of those who did not die of their original cancer of the larynx was compared to the expected survival experience of a population with the same age, birth cohort and sex structure. To date it has been generally assumed for early stage disease that although for some 5-10 years after treatment the survival experience of this patient subgroup might be no different from that expected in the matched group, thereafter the death rate of this subgroup becomes lower than that of the matched group. This implies that surviving cancer patients cured of their disease tend to die of other conditions at a higher than normal rate as they become older, and therefore cancer is never totally cured. Our conclusion is that at least for cancer of the glottic larynx, the answer to the question: 'Can cancer totally be cured?' is 'Yes to at least 15-years post-treatment and also probably to 25 years.'

Disease-Free Survival↗

PubMed1990

[Trends in incidence of cancer in southeast North Brabant and North Limburg during 1975-1986; report from the IKZ/SOOZ cancer registration (Integrated Cancer Center South/Cooperative Organization Oncology Hospitals)].

Trends in the incidence of cancer have been determined in the Southeast of the Netherlands from 1975 to 1986 inclusive by means of the regional SOOZ cancer registry. Age-adjusted registration rates of cancer in males rose rather steeply from more than 371 per 10(5) men-years to 424 in 1982-3 and fell thereafter to 407 per 10(5) in 1986. A similar changing pattern was seen in cancer of the lung, larynx, prostate and kidney and possibly also in cancer of the head and neck. The incidence of colorectal cancer had skin melanoma increased while that of cancer of the stomach fell. Age-adjusted incidence of cancer in females rose steadily from 266 to 290 per 10(5) woman-years. A steady increase was observed for cancer of the lung, breast, bladder and melanoma and temporarily for cancer of the kidney. The incidence of cancer of the stomach and gallbladder fell continuously. These changes in incidence generally corresponded with trends in cancer mortality as registered with the Central Bureau of Statistics. Bias from changes in data collection and coding appears to be negligible, but a certain influence on the registration rates from the markedly increased number of consultants managing cancer patients is likely. Contrasting trends in male and female rates of cancer of the airways illustrate the marked changes in smoking patterns since the sixties.

Female↗

PubMedDate not supplied

Interrelation between Western type cancers and non-Western type cancers as regards their risk variations in time and space. VI. Chronological transition of various cancer risks of the world from 1975 to 1985.

We comparatively investigated the age-adjusted incidence rates (AAIRs) of overall cancers of the world between 1975 and 1985 to see whether or not any consistent change is in progress in the risk for cancer in general on a world scale. Results obtained are summarized as follows: 1) the total male population of the world, but not the total female population, experienced a significant rise in AAIR for cancers of all sites during the above 10 years. 2) In the comparison study of geographical subgroups, the above integral cancer risk significantly increased with time in the male population of Canada, USA-White, USA-Black, European continent (EC)-West, EC-others and Great Britain, and also in the female populations of both USA-Black and Great Britain. In other geographical subgroups the cancer risks for 1985 were also higher than those for 1975, but the differences were not statistically significant. 3) The above increase of cancer risk in general was accounted for by a surplus in weight of the increasing contribution of Western-type cancers over the decreasing contribution of non-Western type cancers to the integral cancer risk of a population. 4) Japan was found to be an exceptional case in that the risk for liver cancer (a non-Western type cancer) increased 3 to 8 fold from 1975 to 1985 in both male and female populations of Japan. Evidence was presented to suggest that the above increase of liver cancer incidence could be related to the persistence of social tension following the first oil crisis in 1973. In summary, the chronological transition patterns of cancer risk in Japan as well as in other parts of the world support our interpretation that social tension linked to the economic recession plays a crucial role in the production of recent changes of cancer risk in the world.

Age Factors↗

PubMed1997

Cancer predisposition, radiosensitivity and the risk of radiation-induced cancers. III. Effects of incomplete penetrance and dose-dependent radiosensitivity on cancer risks in populations.

Recent studies have identified a number of genes in the human genome at which germinal mutations predispose the individuals to one or another type of cancer. These studies also show that not all individuals carrying the mutant genes develop cancers (i.e., the mutant genes are not fully penetrant). At least some of these predisposed genotypes also have a higher sensitivity to cancers induced by ionizing radiation than those who are not so predisposed, which may be dependent on dose. This paper presents an analysis of the impact of such heterogeneity on estimates of cancer risks for an irradiated population. This is done by extending the Mendelian one-locus, two-allele model of cancer predisposition and radiosensitivity developed earlier to allow for incomplete penetrance and dose dependence of radiosensitivity differentials among genotypes. The model is applied to recently published data for breast cancer and hereditary non-polyposis colon cancer using a range of possible values for the strength of predisposition and radiosensitivity differentials. It is shown that, after radiation exposures, the ratio of cancer risks in a heterogeneous population relative to that in a homogeneous population increases with increasing dose, but that the dose dependence of the relative risk diminishes at higher doses. Likewise, the attributable risk (i.e. the proportion of the increase in risk that is due to both increased susceptibility and increased radiosensitivity) and the proportion of attributable risk due to increased radiosensitivity also increase with dose, and the dose dependence of each measurement also diminishes at higher doses. However, when the proportion of cancers due to the susceptible genotypes is small (<10%) (as is likely to be the case for breast cancer in non-Ashkenazi women), the increases in the relative risk and attributable risk are marked only when there are very large increases in cancer susceptibility (>1000-fold) and radiosensitivity (>100-fold) in the susceptible group. When the proportion of cancers due to the susceptible genotypes is appreciable (> or = 10%) (as may be the case for breast cancer in Ashkenazi Jewish women), there may be large increases in the relative risk and attributable risk for comparatively modest increases in cancer susceptibility (>10-fold) and radiosensitivity (>100-fold) in the susceptible subpopulation. For any given combination of strength of predisposition and radiosensitivity differential, incomplete penetrance dilutes the effect.

Breast Neoplasms↗

PubMed2001

Chemoprevention of breast cancer. A joint guideline from the Canadian Task Force on Preventive Health Care and the Canadian Breast Cancer Initiative's Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer.

OBJECTIVE: To assist women and their physicians in making decisions regarding the prevention of breast cancer with tamoxifen and raloxifene. EVIDENCE: Systematic review of English-language literature published from 1966 to August 2000 retrieved from MEDLINE, HealthSTAR, Current Contents and Cochrane Library. VALUES: The strength of evidence was evaluated using the methods of the Canadian Task Force on Preventive Health Care and the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. RECOMMENDATIONS: Women at low or normal risk of breast cancer (Gail risk assessment index < 1.66% at 5 years): There is fair evidence to recommend against the use of tamoxifen to reduce the risk of breast cancer in women at low or normal risk of the disease (grade D recommendation). Women at higher risk of breast cancer (Gail index > or = 1.66% at 5 years): Evidence supports counselling women at high risk on the potential benefits and harms of breast cancer prevention with tamoxifen (grade B recommendation). The cutoff for defining high risk is arbitrary, but the National Surgical Adjuvant Breast and Bowel Project P-1 Study included women with a 5-year projected risk of at least 1.66% according to the Gail index, and the average risk of patients entered in the trial was 3.2%. Examples of high-risk clinical situations are 2 first-degree relatives with breast cancer, a history of lobular carcinoma in situ or a history of atypical hyperplasia. As the risk of breast cancer increases above 5% and the benefits outweigh the harms, a woman may choose to take tamoxifen. The duration of tamoxifen use in such situations is 5 years based on the results from trials of tamoxifen involving women with early breast cancer. If a woman raises concerns or has already been evaluated and is calculated to be at high risk, then individuals experienced and skilled in counselling may discuss the potential benefits and harms of tamoxifen use. Important additional issues: Prevention of breast cancer with raloxifene: Current evidence does not support recommending chemoprevention of breast cancer with raloxifene outside of a clinical trial setting. Screening using the Gail risk assessment index: This index was the main eligibility criterion for enrolling women in the one study that showed potential benefit from chemoprevention. However, it has not been evaluated for use as a routine screening or case-finding instrument; validation of the index is required. Overall, current evidence does not support a shift to its routine use in physicians' offices for screening or case finding. However, when a woman or her physician is concerned about the woman's increased risk of breast cancer, the index can be a useful tool in deciding whether to pursue an in-depth discussion of the potential benefits and harms of chemoprevention. Hence, the approach to identifying women at higher risk who warrant counselling and shared decision-making will vary across practices. (The risk assessment index is available online at http://bcra.nci.nih.gov/brc/). [A patient version of these guidelines appears in Appendix 2.] VALIDATION: The authors' original text was revised by both the Canadian Task Force on Preventive Health Care and the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. The final document reflects a consensus of these contributors. SPONSOR: Health Canada. COMPLETION DATE: February 2001.

Adult↗

PubMed1992

Cancer prevention education in United States medical schools. Cancer Education Survey II: cancer education in United States medical schools.

The Cancer Education Survey collected data from 126 of 128 US Medical Schools on the current status of cancer-related educational activities for undergraduate medical students. The study was conducted by a Supervisory Committee of the American Association for Cancer Education, with funding from the American Cancer Society. The survey obtained data concerning institutional characteristics in support of undergraduate medical student cancer education, ie, administrative structures, current cancer-related curricula, sources of financial support, and anticipated changes in these characteristics. Institutions were also queried on specific topics of cancer prevention, detection, and diagnosis that might be taught as identifiable areas of instruction for medical students. Three-fourths of the institutions had a lecture on the principles of cancer screening, and, among those, nearly three-fourths classified it as a part of a required course or rotation. Detection of common cancers is taught in virtually all institutions. The least likely cancer prevention lecture topics are related to prevention and cessation of smoking, a well-verified cancer risk. Also, no consistent pattern emerges that might indicate that association with a cancer center imparts to a medical school a greater emphasis on delivery of cancer prevention topics.

American Cancer Society↗

PubMedDate not supplied

Guidelines for colonoscopy surveillance after cancer resection: a consensus update by the American Cancer Society and US Multi-Society Task Force on Colorectal Cancer.

Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society (ACS) and US Multi-Society Task Force on Colorectal Cancer addresses only the use of endoscopy in the surveillance of these patients. Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stage II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In nonobstructed colons, colonoscopy should be performed preoperatively. In obstructed colons, double contrast barium enema or computed tomography colonography should be done preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease. After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection. If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that colonoscopy is normal, then the interval before the next subsequent examination should be 5 years. Shorter intervals may be indicated by associated adenoma findings (see Postpolypectomy Surveillance Guideline). Shorter intervals are also indicated if the patient's age, family history, or tumor testing indicate definite or probable hereditary nonpolyposis colorectal cancer. Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence, compared with those with colon cancer. Although effectiveness is not proven, performance of endoscopic ultrasound or flexible sigmoidoscopy at 3- to 6-month intervals for the first 2 years after resection can be considered for the purpose of detecting a surgically curable recurrence of the original rectal cancer.

American Cancer Society↗

PubMed1998

Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: a randomised trial. European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group, the Gruppo Interdisciplinare Valutazione Interventi in Oncologia, and the Japanese Foundation for Cancer Research.

BACKGROUND: There is conflicting evidence on the efficacy of regional adjuvant chemotherapy, via portal-vein infusion (PVI), after resection of colorectal cancer. We undertook a randomised controlled multicentre trial to investigate the efficacy of PVI (500 mg/m2 fluorouracil plus 5000 IU heparin daily for 7 days). METHODS: 1235 of about 1500 potentially eligible patients were randomly assigned surgery plus PVI or surgery alone (control). The patients were followed up for a median of 63 months, with yearly screening for recurrent disease. The primary endpoint was survival; analyses were by intention to treat. FINDINGS: 619 patients in the control group and 616 in the PVI group met eligibility criteria. 164 (26%) control-group patients and 173 (28%) PVI-group patients died. 5-year survival did not differ significantly between the groups (73 vs 72%; 95% Cl for difference -6 to 4). The control and PVI groups were also similar in terms of disease-free survival at 5 years (67 vs 65%) and the number of patients with liver metastases (79 vs 77%). INTERPRETATION: PVI of fluorouracil, at a dose of 500 mg/m2 for 7 days, cannot be recommended as the sole adjuvant treatment for high-risk colorectal cancer after complete surgical excision. However, these results cannot eliminate a small benefit when PVI is used at a higher dosage or in combination with mitomycin.

Aged↗

PubMed1999

Quality of adjuvant chemotherapy in primary breast cancer in a non-trial setting. A comprehensive cancer centre study. The Breast Cancer Group of the Dutch Comprehensive Cancer Centre East (IKO).

The quality of adjuvant chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) and the compliance with guidelines for this treatment were studied in 323 premenopausal patients with node positive breast cancer, who were treated in the Comprehensive Cancer Centre East of The Netherlands (IKO) from 1988 to 1992, outside the setting of a clinical trial. The interval surgery-chemotherapy, the duration of chemotherapy, dose intensity (DI) and relative dose intensity (RDI) of CMF chemotherapy and validations of dose modifications were evaluated. 295 of 323 patients (91%) received adjuvant chemotherapy. CMF chemotherapy was used in 230 patients (78% of the chemotherapy receiving patients). The median time to the start of chemotherapy was 62 (range-35-139) days after surgery. Forty-two per cent of the patients finished their CMF chemotherapy within 168 days. Two per cent of the patients did not finish the six courses of CMF chemotherapy. The mean DI and RDI of the eligible patients in all CMF using hospitals were 80.4 +/- 28.8% and 78.2 +/- 28.4%, respectively. Aberrations of recommended guideline procedures resulted more often in suboptimal treatment than haematological toxicity. Adherence to the guidelines was variable and resulted in suboptimal adjuvant chemotherapy. The median follow-up of the patients treated in hospitals that agreed to the use of CMF was 5 years. The mean RDI of CMF in the eligible patients who relapsed was 72.2 +/- 32.7%, compared with 81.4 +/- 25.2% for the patients who did not relapse (P 0.01), suggesting a possible influence of the RDI on disease free survival. However, when the patients who did not receive chemotherapy were excluded, the mean RDI of the patients who relapsed was 85.0 +/- 12.6% and of the patients who did not relapse 87.4 +/- 12.6%, which was not significantly different (P = 0.20).

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Prevention of oral mucositis or oral candidiasis for patients with cancer receiving chemotherapy (excluding head and neck cancer).

BACKGROUND: Treatment of cancer with chemotherapy is becoming increasingly more effective but is associated with short and long-term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. OBJECTIVES: To evaluate the effectiveness of oral (and topical) prophylactic agents for oral mucositis and oral candidiasis in patients with cancer (excluding head and neck cancer), compared with placebo or no treatment. SEARCH STRATEGY: Computerised MEDLINE, EMBASE, CINAHL, CANCERLIT, the Cochrane Controlled Trials Register and the Cochrane Oral Health Group Specialist Register search up to July 1999. Reference lists from relevant articles were scanned and the authors of eligible studies were contacted to identify trials and obtain additional information. SELECTION CRITERIA: Studies were selected if they met the following criteria: design - random or quasi-random allocation of participants; participants - anyone with cancer receiving chemotherapy (excluding head and neck cancer); interventions - prophylactic agents prescribed to reduce oral conditions arising from cancer or its treatment; outcomes - mucositis and oral candidiasis. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions and outcome measures and results were independently extracted, in duplicate, by two reviewers (JC & HW). Specialist advice was sought to categorise interventions. Authors were contacted for details of randomisation and withdrawals and a quality assessment was carried out using the Jadad criteria (Jadad 1998). The Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using random effects models where significant heterogeneity was detected (P < 0.1). MAIN RESULTS: Thirty-eight reports of trials were initially included. Two were duplicate reports and nine were excluded as there was no useable information. Of the 27 useable studies 14 had data for mucositis comprising 945 randomised patients and 15 included data for oral candidiasis with 1164 randomised patients. Of the eight prophylactic agents used for mucositis only one, ice chips, was effective (Relative risk 0.57, 95% CI 0.43 to 0.77, chi-square for heterogeneity = 0.26 (df = 1), p = 0.61). The NNT to prevent one extra case of mucositis over the baseline incidence using ice chips was 4 (95%CI: 3 to 7). The NNT for when the baseline incidence of mucositis in the population ranges from 50% to 80% are 5 to 4 respectively. There is evidence that antifungal agents which are partially or fully absorbed from the gastrointestinal tract prevent oral candidiasis and that the partially absorbed agents may be more effective than the fully absorbed agents. The RR for partially absorbed agents was 0.13 (95% CI 0.06 to 0.27, chi-square for heterogeneity = 5.3 (df = 3), P = 0. 15). The NNT to prevent one extra case of oral candidiasis over the baseline incidence using partially absorbed drugs was 3 (95% CI: 3 to 5). The NNT for when the baseline incidence of oral candidiasis in the population ranges from 30% to 70% are 4 to 2 respectively. The general reporting of RCT's was poor however the median Jadad score was acceptable and improved further when the authors provided additional information. The sensitivity analysis confirmed the findings for oral candidiasis. REVIEWER'S CONCLUSIONS: There is some evidence that ice chips prevent mucositis. None of the other prophylactic agents included in this review prevented mucositis. There is evidence that prophylactic use of antifungal agents which are absorbed or partially absorbed from the gastrointestinal tract reduce the clinical signs of oral candidiasis, and the partially absorbed drugs may be more effective. Future trials in this area should address the link between oral and general health including outcomes relevant to the patient. Collaboration between medical and dental teams is indicated.

Administration, Oral↗