 Vol.46 n° 2
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Final Results of a Randomized Phase III Trial of Sequential High-Dose Methotrexate, Fluorouracil, and Doxorubicin Versus Etoposide, Leucovorin, and Fluorouracil Versus Infusional Fluorouracil and Cisplatin in Advanced Gastric Cancer: A Trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group
Purpose: To compare the efficacy and tolerability of etoposide, leucovorin, and bolus fluorouracil (ELF) or infusional fluorouracil plus cisplatin (FUP) with that of the reference protocol of fluorouracil, doxorubicin, and methotrexate (FAMTX) in advanced gastric cancer.
Patients and Methods: A total of 399 patients with advanced adenocarcioma of the stomach were randomized and analyzed for toxicity, tumor response, and progression-free and overall survival. Only reviewed and confirmed responses were considered. The analysis of remission was based on assessable patients with documented measurable lesions. The intent-to-treat principle, log-rank test, and Cox regression model were used for the statistical analysis of time-to-event end points.
Results: The overall response rate for 245 eligible patients with measurable disease was 9% with ELF, 20% with FUP, and 12% with FAMTX, with no significant differences. One hundred twelve patients were eligible for efficacy in assessable, nonmeasurable disease. No change was observed in 66% of patients treated with ELF, 56% with FUP, and 55% with FAMTX. Two patients achieved a complete tumor regression (one each for ELF and FAMTX). With a median follow-up time of 4.5 years, the median survival times were 7.2 months with ELF, 7.2 months with FUP, and 6.7 months with FAMTX, respectively, with no significant differences. Nonhematologic and hematologic toxicities of ELF, FUP, and FAMTX were acceptable, with neutropenia being the major toxicity for all three regimens. Seven treatment-related deaths occurred (two with FUP and five with FAMTX).
Conclusion: All three investigated regimens demonstrate modest clinical efficacy and should not be regarded as standard treatment for advanced gastric cancer. New strategies should be considered to achieve a better clinical efficacy in the treatment of advanced gastric cancer.
A preoperative alternating chemotherapy and radiotherapy program for patients with stage IIIA (N2) non-small cell lung cancer
The objective of the present study was to evaluate the feasibility and toxicity of a preoperative alternating chemotherapy and radiotherapy program followed by surgery in stage IIIA non-small cell lung cancer (NSCLC). The tumor response, resection rate, tumor/lymph node downstaging, and survival were also evaluated. The positive predictive value (PPV) in the diagnosis of mediastinal lymph node metastasis was 81% using conventional magnetic resonance imaging (MRI) with short inversion-time inversion recovery (STIR) technique (STIR-MRI) on our criteria. Eligible patients had clinical N2 lesions (stage IIIA) and a World Health Organization (WHO) performance status of 0-2. The treatment program consisted of two courses of preoperative cisplatin, vindesine, and ifosfamide; alternating with radiotherapy, including two courses of 20 Gy radiation. Surgery was performed within 4 weeks after the treatment. Twenty-two patients with stage IIIA (N2) NSCLC (20 men and two women, age 35-71 years) were enrolled into the study. Hematologic and other toxicities were within na acceptable range. Surgery was not indicated for two patients because of distant metastasis: one patient with renal dysfunction and one with pancytopenia during this treatment underwent surgery subsequently. The clinical response rate was 50% (partial response in 11/22). Definitive surgery was indicated for 18 patients resulting in 17 patients with complete resection and one exploratory thoracotomy. A pathologic complete response of the primary tumor occurred in 41% of the patients (seven of 17; without residual tumor), whereas 58% (ten of 17) were pathologic N0. The median survival was 33 months with an actuarial 4-year survival rate of 33% in 17 patients with complete resection and 30 months with 28% 4-year survival rate in all entered patients. A randomized phase-III study using this approach for stage IIIA (clinical N-2 disease) is warranted.
Lung cancer and tobacco control
Just after being committed as President Elect of the International Association for the study of Lung Cancer (IASLC) in August 1994 at the 7th World Conference on Lung Cancer of Colorado Spring, once back home, I felt obliged to inform the Genoa citizens about lung cancer and the close relationship with tobacco smoking. It should also have represented the starting point of my personal action against cigarette smoking to be developed in the whole of Italy. The IASLC board had approved a ten-point program of tobacco control policy, which covered the most important aspects of the problem, from the tax increases on tobacco product to the plans to encourage smoking cessation (1). Actually, it was the last step forward for the IASLC, to enter the present role as the world leader Society on Lung Cancer.
The second decision was represented by the obligation taken by each officer, to personally pursue antismoking campaigns in his own country. Therefore, when the concerned Director of an Italian newspaper offered me two pages of the local Genuese edition. I filled this space with the following four titles. 'Prevention and surgical approach to lung cancer', 'Three weapons for defeating the killer', 'Sparing tissue and pulmonary function through the advanced sleeve bronchial resection and reanastomosis', and 'Tar and nicotine: a ravager combination'. The last issue informed in depth about the various carcinogens produced by tar and nicotine while burning as well as the addictive effect of nicotine and its virus HIV epidemic-like diffusion among the young generations. Lastly, updated information was also given on the industrial process of modern cigarette making. The last information, which I had just received during the Colorado Springs Conference (2-4), was presenting cigarette as a finished good made by a mixture of chemically refined and somewhere else previously extracted nicotine, with minced residual of dried tobacco leaves and stalks, tobacco powder, glues, ashes, vegetable strengthening fibers and finally, a series of wetting, moistening and seasoning of other compounds!
The potential role of amifostine in the treatment of non small cell lung cancer
Amifostine protects healthy tissues but not tumor cells from the damage induced by cytotoxic treatments, particularly ionizing radiations, alkylating and platinating agents. The clinical effectiveness of amifostine has been demonstrated by randomized trials in ovarian and head-and-neck cancer patients treated with chemotherapy with or without radiation therapy. The available pharmacoeconomic data confirm a favorable cost/utility ratio. The majority of non small cell lung cancer (NSCLC) patients receive radio and/or chemotherapy. A role for amifostine in these patients has been hypothesized, and some experiences performed. The aim of this paper is to outline the present role of amifostine in the treatment of NSCLC.
Popularity of less frequent follow up for breast cancer in randomised study: initial findings from the hotline study
Objective: To compare the experiences of patients with breast cancer who were conventionally monitored with those in whom routine follow up was restricted to the time of mammography.
Design: Randomisation to conventional schedule of clinic visits or to visits only after mammography. Both cohorts received identical mammography and were invited to telephone for immediate appointments if they detected symptoms.
Setting: Combined breast clinic, Chelsea and Westminster Hospital.
Subjects: 211 eligible outpatients with a history of breast cancer.
Main outcome measures: Acceptability of randomisation, interim use of telephone and general practitioner, satisfaction with allocation to follow up.
Results: Of 211 eligible patients, 196 (93%) opted for randomisation in the study. Of these, 55 were under 50 years, 78 were diagnosed fewer than five years before, 90 had stage T2-4 tumours, and 71 had involved axillary nodes. Patients who did not participate were more likely to be under 50 years, to be two to five years after diagnosis, and to have had aggressive primary disease. Twice as many patients in both groups expressed a preference for reducing rather than increasing follow up. No increased use of local practitioner services or telephone triage was apparent in the cohort randomised to less frequent follow up by specialists.
Conclusions: Reducing the frequency of routine follow up has so far proved popular among patients with breast cancer at standard risk in this cohort. A multicentre study is needed to determine the effectiveness and cost-effectiveness of routine follow up with respect to disease outcomes.
Relationship between CA 15-3 serum levels and disease extent in predicting overall survival of breast cancer patients with newly diagnosed metastatic disease
In order to study the relationship between circulating levels of CA 15-3 and the disease extent in predicting survival, we prospectively followed 312 breast cancer (BC) patients, from October 1988 to March 1995, from the time of first relapse. CA 15-3 values were assessed before treatment onset. Disease extent was defined as the percentage of liver or lung involvement and the number of bone segments positive at scintigraphy. The covariates were primary tumour characteristics (T, N and hormone receptor status) and patient characteristics at recurrence (menopause, performance status and age). Higher CA 15-3 serum levels were found in patients with visceral metastases or with pleural effusion. A logistic regression model selected disease extent in liver, lung and bone as independent variables for the determination of abnormal CA 15-3 values. Univariate survival analysis confirmed the positive prognostic influence of low CA 15-3 serum levels, absence of visceral metastases and the presence of only one metastatic site. Multivariate Cox's survival analysis selected disease extent in liver, lung, bone and soft tissue but not level of CA 15-3 as prognostic factors. In conclusion, CA 15-3 is not an independent variable in determining survival, its prognostic role being linked to the disease extent. This association suggests that CA 15-3 may be useful in assessing disease extent when this is not easily assessable.
Routine follow up of breast cancer in primary care: randomised trial
Objective: To assess the effect on time do diagnosis of recurrence and on quality of life of transferring primary responsibility for follow up of women with breast cancer in remission from hospital to general practice.
Design: Randomised controlled trial with 18 month follow up in which women received routine follow up either in hospital or in general practice.
Subjects and setting: 296 women with breast cancer in remission receiving regular follow up care at district general hospitals in England.
Main outcome measures: Time between first presentation of symptoms to confirmation of recurrence; quality of life measured by specific dimensions of the SF-36 schedule, the EORTC symptom scale, and hospital anxiety and depression scale.
Results: Most recurrences (18/26, 69%) presented as interval events, and almost half (7/16, 44%) of the recurrences in the hospital group presented first to general practice. The median time to hospital confirmation of recurrence was 21 days in the hospital group (range 1-376 days) and 22 days in the general practice group (range 4-64). The differences between groups in the change in SF-36 mean scores from baseline were small: - 1.8 (95% confidence interval - 7.2 to 3.5) for social functioning, 0.5 (-4.1 to 5.1) for mental health, and 0.6 (-3.6 to 4.8) for general health perception. The change from baseline in the mean depression score was higher in the general practice group at the mid-trial assessment (difference 0.6, 0.1 to 1.2) but there was no significant difference between groups in the anxiety score or the EORTC scales.
Conclusion: General practice follow up of women with breast cancer in remission is not associated with increase in time to diagnosis, increase in anxiety, or deterioration in health related quality of life. Most recurrences are detected by women as interval events and present to the general practitioner, irrespective of continuing hospital follow up.
An initial experience using concurrent paclitaxel and radiation in the treatment of head and neck malignancies
Background: Combined modality therapy plays a central role in the management of head and neck malignancies. This study examimed tje feasibility and preliminary results of treating a group of patients using concurrent bolus paclitaxel (TaxolTM) and radiation therapy.
Methods: Fourteen patients with a median age of 56 years (range 42-81) were treated. Paclitaxel was given every 3 weeks at a dose of 100 mg/m2 concurrently with external beam radiation. The patients treated included those who had failed to achieve a complete response (CR) to induction chemotherapy with cisplatin, 5-fluorouracil, and leucovorin (PFL), or who had locally advanced disease not previously treated.
Results: Median follow-up from the initiation of treatment is 40 months (range 23-48). The majority of patients (13/14) achieved clinical CRs at the primary site. The development of responses was characterized by a long time course. Three patients who were nonresponders (NRs) to induction PFL chemotherapy were treated. One was a clinical CR at the primary site, one did not achieve a CR, and the other had residual disease in the neck. Four patients have failed, one with local-regional disease, one with a marginal failure, one with distant metastases, and one was not rendered disease-free by the treatment. As expected, significant local toxicity was observed. Most patients were managed with the aid of a percutaneous endoscopic gastrotomy (PEG). Two patients experienced significant moist desquamation and required treatment breaks of greater than 1 week.
Conclusion: Paclitaxel can be given on a 3-week schedule at 100 mg/m2 concurrently with radiation. The preliminary results indicate good local responses and acceptable toxicity. This treatment approach merits further study in the treatment of head and neck malignancies, and should be considered as an option in other sites.
Assessing the risk of breast cancer
Each year in the United States, breast cancer is diagnosed in more than 170,000 women. Despite this substantial burden of disease, however, assessment of breast-cancer risk has received very little attention outside the oncology clinic. In primary care, the main result of the recognition of individual variation in breast-cancer risk is the use of age to determine recommendations regarding mammography (older age is a strong risk factor for breast cancer).
Recent developments in the ability to predict and alter breast-cancer risk warrant a new look at the role of assessment of this risk in primary care. Physicians must become adept at evaluating breast-cancer risk and counseling women about its effect on medical decisions. To provide both the rationale and the tools for evaluating breast-cancer risk, this article examines the effects of breast-cancer risk on medical decisions and explains current methods of assessing risk.
Why evaluate breast-cancer risk?
Several important medical decisions may be affected by a woman's underlying risk of breast cancer. These decisions include whether to use postmenopausal hormone-replacement therapy, at what age to begin mammographic screening, whether to use tamoxifen to prevent breast cancer, and whether to perform prophylactic mastectomy to prevent breast cancer.
Randomized Comparison of Cisplatin/Vincristine/Fluorouracil and Cisplatin/Continuous Infusion Doxorubicin for Treatment of Pediatric Hepatoblastoma: A Report From the Children's Cancer Group and the Pediatric Oncology Group
Purpose: Previous studies demonstrated that chemotherapy with either cisplatin, vincristine, and fluorouracil (regimen A) or cisplatin and continuous infusion doxorubicin (regimen B) improved survival in children with hepatoblastoma. The current trial is a randomized comparison of these two regimens.
Patients and Methods: Patients (N = 182) were enrolled onto study between August 1989 and December 1992. After initial surgery, patients with stage I-unfavorable histology (UH; n = 43), stage II (n = 7), stage III (n = 83), and stage IV (n = 40) hepatoblastoma were randomized to receive regimen A (n = 92) or regimen B (n = 81). Patients with stage I-favorable histology (FH; n = 9) were treated with four cycles of doxorubicin alone.
Results: There were no events among patients with stage I-FH disease. Five-year event-free survival (EFS) estimates were 57% (SD = 5%) and 69% (SD = 5%) for patients on regimens A and B, respectively (P = .09) with a relative risk of 1.54 (95% confidence interval, 0.93 to 2.5) for regimen A versus B. Toxicities were more frequent on regimen B. Patients with stage I=UH, stage II, stage III, or stage IV disease had 5-year EFS estimates of 91% (SD = 4%), 100%, 64% (SD = 5%), and 25% (SD = 7%), respectively. Outcome was similar for either regimen within disease stages. At postinduction surgery I, patients with stage III or IV disease who were found to be tumor-free had no events; those who had complete resections achieved a 5-year EFS of 83% (SD = 6%); other patients with stage III or IV disease had worse outcome.
Conclusion: Treatment outcome was not significantly different between regimen A and regimen B. Excellent outcome was achieved for patients with stage I-UH and stage II hepatoblastoma and for subsets of patients with stage III disease. New treatment strategies are needed for the majority of patients with advanced-stage hepatoblastoma.
Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials
Background: Radiotherapy in addition to systemic treatment after mastectomy prolongs survival in high-risk breast-cancer patients. However, adjuvant radiotherapy has a potential association with ischaemic heart disease. We assessed morbidity and mortality from ischaemic heart disease in patients treated with postmastectomy radiotherapy.
Methods: Between 1982 and 1990, we randomly assigned 3083 women at high risk of breast cancer, after mastectomy, adjuvant systemic treatment with (n = 1538) or without (n = 1545) radiotherapy. An anterior photon field was used against the periclavicular region and the axilla. The chest wall was treated through two anterior shaped electron fields, one including the internal mammary nodes. The intended dose was 48-50 Gy in 22-25 fractions, at four to five fractions per week. We obtained information on morbidity and mortality of ischaemic heart disease over a median of 10 years. Analysis was by intention to treat.
Findings: More women in the no-radiotherapy group than in the radiotherapy group died of breast cancer (799 [52.5%] vs 674 [44.2%]), whereas similar proportions of each group died from ischaemic heart disease (13 [0.9%] vs 12 (0.8%]). The relative hazard of morbidity from ischaemic heart disease among patients in the radiotherapy compared with the no-radiotherapy group was 0.86 (95% CI 0.6-1.3), and that for death from ischaemic heart disease was 0.84 (0.4-1.8). The hazard rate of morbidity from ischaemic heart disease in the radiotherapy group compared with the no-radiotherapy group did not increase with time from treatment.
Interpretation: Postmastectomy radiotherapy with this regimen does not increase the actuarial risk of ischaemic heart disease after 12 years.
Chemoprevention of Colorectal Cancer
Colorectal cancer is the second leading cause of cancer-related deaths in the United States. It is estimated that this cancer will develop in 130,000 people in the United States in 2000 and that 56,000 will die from the disease. Surgical resection remains the only curative treatment, and the likelihood of cure is greater when the disease is detected at an earlier pathological stage. Early detection is the goal of screening programs that use periodic examination of stool for occult blood, with or without intermittent endoscopic examination of the bowel. Three randomized studies have shown a reduction in mortality of 15 to 33 percent in those who undergo routine screening. Flexible sigmoidoscopy has been shown in case-control studies to decrease the incidence of and mortality associated with colorectal cancer. Nevertheless, the optimal method for early detection remains uncertain, and despite widely published recommendations for such screening programs, compliance remains poor.
An alternative approach to reducing mortality from colorectal cancer involves the long-term use of a variety of oral agents that can prevent neoplasms from developing in the large bowel. Such pharmacologic prevention, known as chemoprevention, is directed at preventing the development of adenomatous polyps and their subsequent progression to colorectal cancers. Colon cancers are thought to arise as the result of a series of histopathologic and molecular changes that transform normal colonic epithelial cells into a colorectal carcinoma, with an adenomatous polyp as an intermediate step in this process. Polyps occur universally in those with familiar adenomatous polyposis, an autosomal dominant hereditary condition, but this disorder accounts for only 1 percent of cases of colorectal cancer. Adenomatous polyps are found, in approximately 33 percent of the general population by the age of 50 years and in approximately 50 percent by the age of 70 years.
Molecular analyses of colorectal adenomas and carcinomas have led to a genetic model of colon carcinogenesis, in which the development of cancer results not from any single genetic event but from the accumulation of a number of genetic alterations. By interfering with these molecular events, chemoprevention could inhibit or reverse the development of adenomas or the progression from adenoma to cancer. Recent studies have suggested the potential of this approach in patients with familial adenomatous polyposis as well as in persons with no known genetic syndrome but with a history of sporadic polyps. As evidence emerges of the efficacy of chemoprevention in persons at high risk for colorectal cancer, it seems appropriate to consider a similar strategy for the general population.
Laparoscopic Splenectomy for Haematological Diseases: Review of Current Concepts and Opinions
Laparoscopic splenectomy is now currently used by most surgeons in the treatment of many haematological diseases. The operative technique varies depending on the surgeon, but results are usually comparable among published series. We have reviewed 104 papers about laparoscopic splenectomy for haematological diseases and paid particular attention to surgical aspects and early postoperative results. We searched MEDLINE from January 1989 to April 1998, and of the 104 papers that we found 41 fulfilled our criteria of large series published in peer-reviewed journals that had been cited often. They usually compared laparoscopic and open splenectomy and focused on common problems (such as accessory spleens) and technical aspects (such as bleeding).
Laparoscopic splenectomy is reported by most authors to be as safe and effective as open splenectomy for haematological diseases. It also has several advantages over the open approach, such as shorter and less complicated postoperative stay with better cosmetic results and more rapid return to full activities.
Key words: laparoscopic surgery, splenectomy, haematology, lymphoma, leukaemia, anaemia, idiopathic thrombocytopenic purpura, complications, laparotomy.
Sentinel Lymph Node Biopsy and Axillary Dissection in Breast Cancer: Results in a Large Series
Background: Axillary lymph node dissection is an established component of the surgical treatment of breast cancer, and is an important procedure in cancer staging; however, it is associated with unpleasant side effects. We have investigated a radioactive tracerguided procedure that facilitates identification, removal, and pathologic examination of the sentinel lymph node (i.e., the lymph node first receiving lymphatic fluid from the area of the breast containing the tumor) to predict the status of the axilla and to assess the safety of foregoing axillary dissection if the sentinel lymph node shows no involvement.
Methods: We injected 5-10 MBq of 99mTc-labeled colloidal particles of human albumin peritumorally in 376 consecutive patients with breast cancer who were enrolled at the European Institute of Oncology during the period from March 1996 through March 1998. The sentinel lymph node in each case was visualized by lymphoscintigraphy, and its general location was marked on the overlying skin. During breast surgery, the sentinel lymph node was identified for removal by monitoring the acoustic signal from a hand-held gamma ray-detecting probe. Total axillary dissection was then carried out. The pathologic status of the sentinel lymph node was compared with that of the whole axilla.
Results: The sentinel lymph node was identified in 371 (98.7%) of the 376 patientss and accurately predicted the state of the axilla in 359 (95.5%) of the patients, with 12 false-negative findings (6.7%; 95% confidence interval = 3.5% - 11.4%) among a total of 180 patients with positive axillary lymph nodes.
Conclusions: Sentinel lymph node biopsy using a gamma ray-detecting probe allows staging of the axilla with high accuracy in patients with primary breast cancer. A randomized trial is necessary to determine whether axillary dissection may be avoided in those patients with an uninvolved sentinel lymph node.
Can dietary factors influence prostatic disease?
Prostate cancer is now one of the most commonly diagnosed cancers in the West [1]; worldwide, the incidence is rising annually by 2-3% [2]. In North American men prostate cancer is now the second most commonly diagnosed cancer after skin cancer, and the second most common cause of death from cancer after that of the lung. There were 317 000 new cases diagnosed in the USA in 1996 and 41 000 men died from the disease that year [3].
There is considerable geographical variation in the age-adjusted incidence of cancer of the prostate [4]. However, autopsy studies reveal that the incidence of latent carcinoma of the prostate is the same in men from both East and West [5]. The incidence of clinically malignant disease is highest in black North American men, some 30-fold greater than in Japanese men, and 120 times greater than that seen in Chinese men in Shanghai [4]. For Japanese migrants to North America the incidence increases to about half that of the indigenous population within one or two generations [6]. The epidemiological phenomena observed in migrating populations appears sufficiently quickly to suggest that dietary and environmental factors, rather than genetic ones, are responsible.
Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population-based study
Background: Heterocyclic amines formed in cooked meat and fish are carcinogenic in animal models and form DNA adducts in human beings. We undertook a study to assess whether these substances are related to the risks of cancer in the large bowel and urinary tract.
Methods: In a population-based case-control study, cases were identified from the Swedish cancer registry. Controls were randomly selected from the population register. Information on intake of various foods and nutrients was assessed by questionnaire, with photographs of foods cooked at various temperatures. We measured the content of heterocyclic amines in foods cooked under these conditions.
Findings: Information was retrieved from 553 controls, 352 cases of colon cancer, 249 cases of rectal cancer, 273 cases of bladder cancer, and 138 cases of kidney cancer. The response rate was 80% for controls and 70% for cases. The estimated daily median intake of heterocyclic amines was 77 ng for controls, and 66 ng, 63 ng, 96 ng, and 84 ng for cases with cancer of the colon, rectum, bladder, and kidney, respectively. The relative risk for the intake of heterocyclic amines (highest vs lowest quintile) was 0.6 (95% CI 0.4-1.0) for colon cancer, 0.7 (0.4-1.1) for rectal cancer, 1.2 (0.7-2.1) for bladder cancer, and 1.0 (0.5-1.9) for kidney cancer. Seven cases, but no controls, had an estimated daily intake of heterocyclic amines above 1900 ng.
Interpretation: Intake of heterocyclic amines, within the usual dietary range in this study population, is unlikely to increase the incidence of cancer in the colon, rectum, bladder, or kidney. For daily intakes above 1900 ng, our data are consistent with human carcinogenicity, but the precision was extremely low.
Tomatoes, Tomato-Based Products, Lycopene, and Cancer: Review of the Epidemiologic Literature
The epidemiologic literature in the English language regarding intake of tomatoes and tomato-based products and blood lycopene (a compound derived predominantly from tomatoes) level in relation to the risk of various cancers was reviewed. Among 72 studies identified, 57 reported inverse associations between tomato intake or blood lycopene level and the risk of cancer at a defined anatomic site; 35 of these inverse associations were statistically significant. No study indicated that higher tomato consumption or blood lycopene level statistically significantly increased the risk of cancer at any of the investigated sites. About half of the relative risks for comparisons of high with low intakes or levels for tomatoes or lycopene were approximately 0.6 or lower. The evidence for a benefit was strongest for cancers of the prostate, lung, and stomach. Data were also suggestive of a benefit for cancers of the pancreas, colon and rectum, esophagus, oral cavity, breast, and cervix. Because the data are from observational studies, a cause-effect relationship cannot be established definitively. However, the consistency of the results across numerous studies in diverse populations, for case-control and prospective studies, and for dietary-based and blood-based investigations argues against bias or confounding as the explanation for these findings. Lycopene may account for or contribute to these benefits, but this possibility is not yet proven and requires further study. Numerous other potentially beneficial compounds are present in tomatoes, and, conceivably, complex interactions among multiple components may contribute to the anticancer properties of tomatoes. The consistently lower risk of cancer for a variety of anatomic sites that is associated with higher consumption of tomatoes and tomato-based products adds further support for current dietary recommendations to increase fruit and vegetable consumption.
Stage at Diagnosis and Treatment Patterns Among Older Women With Breast Cancer
Context: Few studies have compared patterns of care in health maintenance organization (HMO) and fee-for-service (FFS) settings.
Objective: To examine breast cancer stage at diagnosis and, for those at na early stage, treatment patterns for elderly women in HMO and FFS settings.
Design: Cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) program linked to Medicare enrollment records.
Settings and Participants: Women aged 65 years or older residing in 11 geographic areas who were newly diagnosed as having breast cancer between 1988 and 1993.
Main Outcome Measures: Standardized percentage of cases diagnosed at late stages for HMO vs FFS; standardized percentage of early-stage cases undergoing initial treatment with breast-conserving surgery (BCS); and, among BCS cases, standardized percentage receiving adjuvant radiation therapy. Standardization was achieved through logistic regression, controlling for patient demographics, cancer history, county of residence, year of diagnosis, and educational attainment at the census tract level. Analyses of treatment patterns were controlled for stage at diagnosis and tumor size.
Results: The HMO enrollees were less likely to have breast cancer diagnosed at late stages than FFS patients (HMO, 7.6%; FFS, 10.8%; difference, - 3.2% [95% confidence interval (CI), - 4.2% to -2.2%]). Among early-stage cases, the percentages undergoing BCS were similar in HMO and FFS settings overall (HMO, 38.4%; FFS, 36.8%; difference, 1.6% [95% CI, 0.0%-3.2%]); percentages varied markedly at the individual plan level. Among women undergoing BCS, HMO enrollees were significantly more likely to receive radiation therapy but, again, results varied by plan (HMO, 69.0%; FFS, 63.7%; difference, 5.3% [95% CI, 2.9%-7.7%]). In general, use of BCS and radiation therapy was substantially higher than that found in an earlier study examining cases diagnosed between 1985 and 1989.
Conclusions: Treatment of early-stage breast cancer in HMOs often differs from local FFS patterns, but not in a consistent way. During the period of our study, elderly HMO enrollees did not appear to have systematic access problems with adjuvant radiation therapy following BCS compared with women in na FFS setting.
The clinical utility of the Revised European - American Lymphoma (R.E.A. L.) Classification: Preliminary results of a prospective study in patients with non-Hodgkin's lymphoma from a single centre
Background: The clinical applicability of the Revised European-American Lymphoma (R.E.A.L.) Classification has been demonstrated in several retrospective studies. The present, ongoing study was initiated to evaluated the clinical and pathological utility of the R.E.A.L. Classification compared with the Working Formulation (WF) in a prospective fashion, in an unselected patient population treated at a single institution.
Patients and methods: Prospective data were collected on 596 biopsies from 557 patients referred with an initial diagnosis of lymphoma. After initial histologic review, 465 biopsies from 441 patients were confirmed as non-Hodgkin's lymphoma (NHL), 412 of which could be classified in R.E.A.L. and WF.
Results: According to WF criteria, 25% were low grade, 58% intermediate grade and 2% high grade. 14% could not be allocated to a WF subtype. According to R.E.A.L., 46% were diffuse large B cell, 19% follicle centre lymphoma, 6% marginal zone, 6% small lymphocytic, 4% mantle cell, and 3% T-cell anaplastic large cell. For those with B-cell NHL, 7% were unclassifiable in WF compared with 1% in R.E.A.L. Corresponding figures for T-cell NHL were 68% and 3%, respectively.
Conclusions: Preliminary results confirm the clinical utility of the R.E.A.L. Classification in a single institution setting, demonstrating that cases were more readily sub-typed in R.E.A.L. compared with WF. Frequencies are comparable with I.L.S.G. data. Further follow up with large patient numbers is on-going to analyse survival data with reference to clinical prognostic factors.
Key words: lymphoma, non-Hodgkin's, R.E.A.L. Classification.
p53 and chemosensitivity
Background: Although hematologic malignancies and some solid tumors such as germ cell tumors and pediatric malignancies can be cured by cytotoxic treatment, the most prevalent solid tumors are relatively resistant to these interventions. Apoptosis is involved in the cell kill of anticancer drugs and p53 is believed to be of principal importance in this process. However p53 also plays a role in cell cycle arrest and DNA repair, cellular processes that can decrease the sensitivity to chemotherapy. Therefore, p53 may play a dual role after exposure to cytotoxic treatment, activating either mechanisms that lead to apoptosis or launching processes directing to DNA repair and survival of the cell.
Design: In this article, we review in details the p53 functions involved in the mediation of chemosensitivity. The preclinical and clinical data published in the recent years about the relation between p53 and chemosensitivity are discussed and the potential pitfalls associated to most of these studies, and that may account for the contradictory results produced so far are also mentioned.
Key words: apoptosis, chemosensitivity, cytotoxicity, p53
Breast cancer risk among women with psychiatric admission with affective or neurotic disorders: a nationwide cohort study in Denmark
Summary: There is a considerable interest in the possible relationship between psychosocial factors and the onset of breast cancer. This cohort study was based upon two nationwide and population-based central registers: The Danish Psychiatric Central Register, which contains all cases of psychiatric admissions, and the Danish Cancer Registry, which contains all cases of cancer. The register-linkage was accomplished by using a personal identification number. The study population comprised all women admitted to psychiatric departments or psychiatric hospitals in Denmark between 1969 and 1993 with an affective or a neurotic disorder. Overall, 66 648 women comprising 199 910 admissions and 775 522 person-years were included. The incidence of breast cancer in the cohort was compared with the national breast cancer incidence rates adjusted for age and calendar time. In all, 1270 women with affective or neurotic disorders developed breast cancer subsequent to the first admission as compared with the 1242 women expected, standardized incidence ratio (SIR) = 1.02 (95% confidence interval 0.97 - 1.08). None of the hypothetical risk factors: type of diagnosis, age or calendar period at cohort entry, age at breast cancer, alcohol abuse, alcohol/drug abuse without further specification, total number of admissions, total length of admissions, or time from first admission showed a statistically significant effect on the relative risk of breast cancer. We found no support for the hypothesis that women admitted to a psychiatric department with an affective or a neurotic disorder subsequently have na increased risk of breast cancer.
Keywords: neoplasm breast; aetiology; affective disorder; neurotic disorders; alcohol abuse; non-specified abuse
Phase II study of cisplatin and 5-fluorouracil in previously treated metastatic breast cancer: an Eastern Cooperative Oncology Group study (PA 185)
Purpose: The present study was conducted to investigate the efficacy and toxicity of a cisplatin and 5-fluorouracil (5-FU) combination in previously treated advanced breast cancer.
Methods: Thirty-six women with recurrent metastatic breast cancer were entered on a phase II study of 5-FU 1000 mg/m²/day given intravenously as a continuous infusion on days 1-3 and cisplatin 30 mg/m²/day given intravenously over 1 h on days 2-4, repeated every 21 days. All subjects had received one previous chemotherapy regimen for metastatic disease and either progressed during treatment or relapsed after responding to previous chemotherapy. Fourteen patients had also received previous adjuvant chemotherapy, 17 patients had previous radiation therapy, and 29 patients had previous hormonal therapy.
Results: Among 32 response-evaluable patients, there were 10 partial remissions (31%) and 1 complete remission (3%), with an overall objective response rate of 34%. Median duration of response was 4 months. Median survival was 10.5 months for responders and 9.5 months for the entire group. Toxicity was mild to moderate in most patients. Overall twelve patients experienced grade 3 toxicity (10 hematologic, 1 mucositis, and 2 nausea). Here were no grade 4 or 5 toxicities.
Conclusion: Infusional cisplatin and 5-FU is a well tolerate and active regimen in women with previously treated advanced breast cancer.
Key words: chemotherapy, cisplatin, 5-fluouracil, metastatic breast cancer.
Economic evaluations of systemic adjuvant breast cancer treatments: methodological issues and a critical review
During the last 2 decades economic evaluations became more and more important. The reason for this is 2-fold. First of all, in this period, there was a high increase in health care costs. Secondly, the available resources are limited. Therefore, it became increasingly important that the available resources were used in an optimal way, that is, in such a way that the most benefit for the patients is obtained. To realise this maximum benefit, economic evaluation is an important tool. Economic evaluation can help to make clear which health care interventions give good value for money, that is, which interventions give a high benefit in relation to what they cost.
Economic evaluations are particularly important in health care areas in which considerable costs are induced. Breast cancer is a major public health problem and therefore leads to considerable costs. Annually, in the USA 183 000 women are diagnosed and 46 000 women are dying of breast cancer [1]. In 1993, the health care costs of initial, continuing and terminal breast cancer treatment in the USA were estimated to be US$ 10813, 1084 and 17 686 per patient, respectively [2].
In the Netherlands, breast cancer is the most frequent invasive tumour among females and accounts for one-third of all cancers in females [3]. The total health care costs of breast cancer in the Netherlands were estimated at 253 million Dutch guilders in 1988, which is about 13% of the total health care costs of cancer [4].
In this article, first we will address some basic concepts of economic evaluations. Afterwards, a review will be given of economic evaluations of adjuvant treatments for breast cancer. After describing briefly which treatments belong to the adjuvant treatments of breast cancer, the economic evaluations of systemic adjuvant breast cancer treatments will be critically examined. Finally, the results of the economic evaluations and the merit of those results will be discussed.
This article was written with clinical researches in mind. The aim of this article is to show clinicians which issues are important in economic evaluations, particularly when they are performed for adjuvant breast cancer treatments.
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Revista Brasileira de Cancerologia - Volume 46 n°2 Abr/Mai/Jun 2000