Patti A. Groome

The IASLC Lung Cancer Staging Project: Proposals for the Revision of the TNM Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours

Introduction: The seventh edition of the TNM Classification of Malignant Tumors is due to be published early in 2009. In preparation for this, the International Association for the Study of Lung Cancer established its Lung Cancer Staging Project in 1998. The recommendations of this committee for changes to the T, N, and M descriptors have been published. This report contains the proposals for the new stage groupings. Methods: Data were contributed from 46 sources in more than 19 countries. Adequate data were available on 67,725 cases of non-small cell lung cancer treated by all modalities of care between 1990 and 2000. The recommendations for changes to the T, N, and M descriptors were incorporated into TNM subsets. Candidate stage groupings were developed on a training subset and tested in a validation subset. Results: The suggestions include additional cutoffs for tumor size, with tumors >7 cm moving from T2 to T3; reassigning the category given to additional pulmonary nodules in some locations; and reclassifying pleural effusion as an M descriptor. In addition, it is suggested that T2b N0 M0 cases be moved from stage IB to stage IIA, T2a N1 M0 cases from stage IIB to stage IIA, and T4 N0–1 M0 cases from stage IIIB to stage IIIA. Conclusions: Such changes, if accepted, will involve a reassessment of existing treatment algorithms. However, they are based on an intensive and validated analysis of the largest database to date. The proposed changes would improve the alignment of TNM stage with prognosis and, in certain subsets, with treatment.

The IASLC Lung Cancer Staging Project: Validation of the Proposals for Revision of the T, N, and M Descriptors and Consequent Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours

Introduction: In 1996, the International Association for the Study of Lung Cancer (IASLC) launched a worldwide TNM staging project to inform the next edition (seventh) of the TNM lung cancer staging system. In this article, we describe the methods and validation approaches used and discuss the internal and external validity of the recommended changes. Methods: The International Staging Committee agreed on a number of general principles that guided the decision-making process. Internal validity was addressed by visually assessing the consistency of Kaplan-Meier curves across database types, geographic regions and addressing external validity, by assessing the similarity of curves generated using the population-based Surveillance Epidemiology and End Results cancer registry data to those generated using the project database. Cox proportional hazards regression was used to calculate hazard ratios between the proposed stage groupings with adjustment for cell type, sex, age, and region. Results: Calls for data by the International Staging Committee resulted in the creation of an international database containing information on more than 100,000 cases. The present work is based on analyses of the 67,725 cases of non-small cell lung cancer. Validation checks were robust, demonstrating that the suggested staging changes are stable within the data sources used and externally. For example, suggested changes based on tumor size were well supported, with statistically significant hazard ratios ranging from 1.14 to 1.51 between adjacent pairs in the Surveillance Epidemiology and End Results data. Conclusions: Lung cancer stage definitions have never been subjected to such an intense validation process. We do accept, however, that this work is limited in ways that can only be addressed by a prospective database, which we intend to develop. In the meantime, we think that this new system will greatly improve the usefulness of TNM lung staging across all of its purposes.

Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries.

PURPOSE To compare the risk for fatal myocardial infarction (MI) after adjuvant radiotherapy (RT) for left-sided breast cancer with the risk for MI after adjuvant RT for right-sided breast cancer. METHODS We studied women with local- and regional-stage breast cancer diagnosed from 1973 to 1992 from the Surveillance, Epidemiology, and End-Results (SEER) cancer registries. We performed life-table analysis, the log-rank test, and Cox proportional hazards regression to compare the time to fatal MI from diagnosis between left-sided and right-sided cases, censoring deaths from other causes. RESULTS Among irradiated patients, the relative risk (RR) for fatal MI in women with left-sided breast cancer was 1.17 (95% confidence interval [CI], 1.01 to 1.36), controlling for age, compared with those with right-sided breast cancer. The RR for fatal MI among left-sided cases was increased for those under the age of 60 years (RR = 1.98; 95% CI, 1.31 to 2.97) compared with right-sided cases, but not at age 60 years or older. Among women with irradiated regional-stage cancer who were younger than 60 years of age, the risk was significantly increased (RR = 2.24; 95% CI, 1.38 to 3.64) for those with left-sided compared with right-sided breast cancer, but not among patients aged 60 years or older. Among irradiated local-stage cases, the risk for those with left-sided breast cancer was not significantly elevated in either age category. Analysis of 5-year conditional survival cohorts showed an increased risk for irradiated left-sided cases among women younger than 60 years of age in the 10- to 15-year conditional survival cohort (RR = 5.28; 95% CI, 1.82 to 15.3). CONCLUSION Adjuvant RT for left-sided breast cancer diagnosed in women younger than 60 years of age is associated with a higher risk for fatal MI 10 to 15 years later compared with adjuvant RT for right-sided cases.

Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer: a population-based study in Ontario, Canada.

PURPOSE To compare the risk of mortality from myocardial infarction (MI) after left-sided postlumpectomy radiotherapy (RT) to the risk after right-sided postlumpectomy RT. METHODS We conducted a population-based cohort study of cases of invasive female breast cancer in Ontario, diagnosed between January 1, 1982 and December 31, 1987 (n = 25,570). Records of the Ontario Cancer Registry (OCR) were linked to hospital procedure and discharge abstracts and to RT records from Ontario cancer centers. A case was labelled as lumpectomy if this was the maximum breast surgery within 4 months of diagnosis. Postlumpectomy RT occurred up to 1 year postdiagnosis. Laterality was assigned from the laterality descriptor of the RT records. A case was labelled as having had a fatal MI if ICD code 410 (myocardial infarction) was recorded as the cause of death in the OCR. We used logistic regression to compare the likelihood of utilization of: 1. Dose per fraction > 2.00 Gy; 2. cobalt vs. linac; and 3. boost RT. We used life table analysis and the log rank test comparing the time to fatal MI from diagnosis of breast cancer between women who received left-sided postlumpectomy RT and women who received right-sided. We used Cox proportional hazards models to study the relative risk for left-sided cases overall, and stratified by age, RT characteristics, and among conditional survival cohorts. RESULTS Postlumpectomy RT was received by 1,555 left-sided and 1,451 right-sided cases. With follow-up to December 31, 1995, 2% of women with left-sided RT had a fatal MI compared to 1% of women with right-sided RT. Comparison of the time to failure between women who had left-sided RT and women who had right-sided RT showed the left-sided RT group to be associated with a higher risk of fatal MI (p = 0.02). Adjusting for age at diagnosis, the relative risk for fatal MI with left-sided postlumpectomy RT was 2.10 (1.11, 3.95). CONCLUSION Among women who received postlumpectomy RT for breast cancer in Ontario between 1982-1987, left-sided postlumpectomy RT was associated with a higher risk of fatal MI compared to right-sided.

The process for continuous improvement of the TNM classification

The TNM classification is a worldwide benchmark for reporting the extent of malignant disease and is a major prognostic factor in predicting the outcome of patients with cancer. The objectives for cancer staging were defined by the International Union Against Cancer (UICC) TNM Committee almost 50 years ago and are still broadly applicable today. To keep pace with the modern demands of evidence‐based practice, the UICC introduced a structured process for introducing changes to the TNM classification. The elements of the TNM process were determined to include the development of unambiguous criteria for the information and documentation required to consider changes in the classification, establishment of a well‐defined process for the annual review of relevant literature, formation of site‐specific expert panels, and the participation of experts from all over the world in the TNM review process. Communication between the oncology community and those involved in the TNM classification was established as being essential to the success of the process. The process, which was introduced in 2002, will be tested over the next 3–4 years and evaluated. In addition to the formal process, individual initiative, involvement by the national staging committees, and group consensus are required. Furthermore, increased involvement by the experts should improve the understanding and dissemination of the TNM classification. Cancer 2004;100:1–5. Published 2003 by the American Cancer Society.

Socioeconomic status and cancer survival in Ontario.

BACKGROUND AND PURPOSE It is known that the socioeconomic status (SES) of the patient is associated with cancer survival in the United States. The purpose of this study was to determine whether the association between SES and survival is also present in Canada, a society with a comprehensive, universal, health insurance program. METHODS A population-based cancer registry was used to identify the 357,530 cases of invasive cancer diagnosed in the Canadian province of Ontario between 1982 and 1991. Information from the 1986 Canadian census was linked to the registry and used to describe the SES of the area in which each patient resided. Cox regression was used to describe the association between median household income and survival while controlling for age, sex, and the region in which the patient resided. The Cox model was fitted in a competing risk framework to assess the association between income and the probability of specific causes of death. RESULTS Lung cancer and cancers of the head and neck region were relatively more common in poor-income communities, and cancers of the breast, CNS, and testis were relatively more common in richer communities. A strong and statistically significant association between community income and survival was observed in cancers of the head and neck region, cervix, uterus, breast, prostate, bladder, and esophagus. Smaller, but significant associations were seen in cancers of the lung and rectum. No significant association between community income and survival was observed in cancers of the stomach, colon, pancreas, or ovary. Analysis of the cause of death showed that community income is associated both with the probability of death from cancer and with the probability of death from other causes. CONCLUSION Although Canadas health care system was designed to provide equitable access to equivalent standards of care, it does not prevent a difference in cancer survival between rich and poor communities.

Associations Between Community Income and Cancer Survival in Ontario, Canada, and the United States

PURPOSE The objectives of this study were as follows: (1) to compare the magnitude of the association between socioeconomic status (SES) and cancer survival in the Canadian province of Ontario with that in the United States (U.S.), and (2) to compare cancer survival in communities with similar SES in Ontario and in the U.S. METHODS The Ontario Cancer Registry provided information about all cases of invasive cancer diagnosed in Ontario from 1987 to 1992, and the Surveillance, Epidemiology and End Results Registry (SEER) provided information about all cases diagnosed in the SEER regions of the U.S. during the same time period. Census data provided information about SES at the community level. The product-limit method was used to describe cause-specific survival. Cox proportional hazards models were used to describe the association between SES and the risk of death from cancer. RESULTS There were significant associations between SES and survival for most cancer sites in both the U.S. and Ontario, but the magnitude of the association was usually larger in the U.S. In the poorest communities, there were significant survival advantages in favor of cancer patients in Ontario for many disease groups, including cancers of the lung, head and neck region, cervix, and uterus. However, in upper- and middle-income communities, there were significant survival advantages in favor of the U.S. for all cases combined and for several individual diseases, including cancers of the breast, colon and rectum, prostate, and bladder. CONCLUSION The association between SES and cancer survival is weaker in Ontario than it is in the U.S. This is due to a combination of better survival among patients in the poorest communities and worse survival among patients in the wealthier communities of Ontario relative to those in the U.S.

Does a centralized radiotherapy system provide adequate access to care

PURPOSE In the Canadian province of Ontario, all radiotherapy is provided by a centrally managed provincial network of nine cancer centers. The primary goal of this study was to determine whether this highly centralized radiotherapy system provides adequate and equitable access to care for the provinces dispersed population. METHODS The Ontario Cancer Registry (OCR) was used to identify 295,386 cases of invasive cancer, excluding nonmelanoma skin cancer, which were diagnosed in Ontario between 1984 and 1991. Electronic radiotherapy records from each of the provinces radiotherapy centers were linked to the registry at the level of the individual case. RESULTS The proportion of incident cases treated with radiotherapy was 18.8% at 4 months after diagnosis, 23.7% at 1 year, 25.8% at 2 years, 28.2% at 5 years, and 29.1% at 8 years. These rates of radiotherapy use are much lower than the accepted national and international targets, and lower than rates reported from other jurisdictions. The rate of radiotherapy use at 1 year varied significantly from county to county across Ontario (range, 18.6% to 32.4%; P < 10(-6)), and the highest rates were recorded in communities close to radiotherapy centers. There was a common geographic pattern of rate variations among several disease groups, including breast cancer, lung cancer, the genitourinary malignancies, and the gastrointestinal malignancies. CONCLUSION The low and uneven rates of radiotherapy use across the province indicate that Ontarios centralized radiotherapy system does not, at present, provide adequate or equitable access to care.

Factors Affecting the Use of Palliative Radiotherapy in Ontario

PURPOSE To describe the use of palliative radiotherapy (PRT) and to identify factors associated with the use of PRT. MATERIALS AND METHODS The Ontario Cancer Registry was used to identify 193,253 adult patients who died of cancer between 1986 and 1995. Radiotherapy records from all Ontario cancer centers and the data on socioeconomic status (SES) from the Canadian Census were linked to the Ontario Cancer Registry data. The proportion of cases who received at least one course of PRT at any time within 2 years of death (PRT(2Y)) was used as a primary measure of the use rate of PRT. RESULTS Overall, 26.4% of cases underwent at least one course of PRT. PRT(2Y) remained relatively constant over the study period. PRT(2Y) was disease-specific and ranged from 4% for pancreatic cancer to 41% for prostate cancer. Age was negatively associated with PRT(2Y) (adjusted odds ratio [OR], 4.5 for the youngest group), and SES was positively associated with PRT(2Y) (adjusted OR, 1.2 for patients from wealthy communities). Patients who were initially diagnosed in a hospital affiliated with a cancer center (adjusted OR, 1.4) or who lived in a county in which a cancer center is located (adjusted OR, 1.2), or who resided in certain regions (adjusted OR, 1.20 for Hamilton and 1.17 for Kingston), were more likely to be treated with PRT. CONCLUSION The use of PRT varied across the dispersed population in Ontario and was influenced by factors unrelated to the patients needs. An effort should be made to reduce barriers to access for disadvantaged groups.

The impact of comorbidity on the survival of patients with squamous cell carcinoma of the head and neck

In North America, cigarette smoking and/or alcohol consumption not only cause head and neck cancer, they also cause many of the other diseases, illnesses, and conditions, also known as comorbidities, frequently found in our patients. Comorbidities can influence treatment decision making and treatment outcome. The aim of this study is to quantify the increased risk of comorbidity in our patients.