Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances

TNM Staging For Melanoma Skin Cancer

The stage of a melanoma skin cancer tells you how thick it is and if it has spread. It helps your doctor decide the best treatment for you. TNM stands for Tumour, Node, Metastasis. TNM staging for melanoma skin cancer is complicated. Talk to your doctor or specialist nurse about your diagnosis. They can help you to understand more about the TNM stage of the melanoma. Doctors might also use a number staging system. This has 5 different stages - from stage 0 to stage 4. They might also use a scale to describe how deeply the melanoma has grown into your skin. This is called the Breslow thickness. Tumour (T) Tumour describes the thickness of the melanoma. It also describes if the skin over the tumour is broken when looked at under a microscope (ulcerated) or not. There are 6 main stages of tumour thickness in melanoma – Tis to T4: Tis means the melanoma cells are only in the very top layer of the skin surface. It is called melanoma in situ. T0 means your doctors can no longer see the melanoma at the place it started (primary site). Or tests show that you have a melanoma that has spread, but your doctors do not know where it started. T1 means the melanoma is 1 mm thick or less. Doctors split T1 into T1a and T1b.   T1a means the melanoma is less than 0.8 mm thick and the skin over it does not look ulcerated. T1b means either: the melanoma is less than 0.8 mm thick and is ulcerated the melanoma is between 0.8 mm and 1 mm thick and may or may not be ulcerated T2 means the melanoma is more than 1 mm thick up to 2 mm thick. T3 means the melanoma is more than 2 mm thick up to 4 mm thick. T4 means the melanoma is more than 4 mm thick. T2, T3 and T4 melanomas are further divided into a and b. This depends on whether the melanoma is ulcerated or not - a means without ulceration, b means with ulceration. The skin is made up of 2 main layers. These are called the epidermis and dermis. The thickness of the epidermis and dermis varies depending on which part of the body the skin is covering. This means that how far a melanoma goes into these layers will also vary.  Node (N) Node describes whether cancer cells are in the nearby lymph nodes. Where a cancer starts is called the primary tumour. Areas of cancer that have spread to another part of the body from the primary tumour are called metastases. Doctors look for cancer cells in the nearby lymph nodes. In melanoma, they also look at whether the cancer has spread to the area between the primary tumour and the nearby lymph nodes. They use different terms for this. These are: microsatellite metastases satellite metastases in-transit metastases Microsatellite metastases mean that your doctor can see melanoma cells next to the primary tumour when they look at it under a microscope. These cancer cells are not touching the primary tumour. Satellite metastases mean that the melanoma cells have visibly spread to an area less than 2 cm away from the primary tumour. These cells are not touching the primary tumour. In-transit metastases mean the melanoma has spread to an area more than 2 cm away from the primary tumour. But it has not reached the nearby lymph nodes. There are 4 main N stages in melanoma: N0 means there are no melanoma cells in the nearby lymph nodes. N1 means one of the following: there are melanoma cells in one lymph node there are in-transit, satellite or microsatellite metastases N2 means there are melanoma cells in either: 2 or 3 lymph nodes one lymph node and there are also in-transit, satellite or microsatellite metastases N3 means there are melanoma cells in: 4 or more lymph nodes any number of lymph nodes and they have stuck to each other (matted lymph nodes) 2 or more lymph nodes and there are in-transit, satellite or microsatellite metastases N1, N2 and N3 can each be further divided into a, b or c. This depends on whether your doctor found the spread to the lymph nodes on your scans or in a sentinel lymph node biopsy. And whether you have any in-transit, satellite or microsatellite metastases. Metastasis (M) Metastasis (M) describes whether the cancer has spread to a different part of the body such as the liver or lungs. There are 2 stages of metastasis – M0 and M1: M0 means the cancer hasn't spread to another part of the body. M1 means the cancer has spread to another part of the body.  M1 can be further divided into a, b, c or d. This depends on which parts of the body the cancer has spread to. Treatment The stage of the cancer helps your doctor decide what treatment you need. Treatment also depends on where the melanoma is and your general health and fitness. Surgery is the main treatment for people with melanoma that has not spread (early melanoma). You usually have other treatment if: the melanoma is at high risk of coming back you are unable to have surgery the melanoma has spread to another part of the body (advanced melanoma) Other treatments include: You may have treatment as part of a clinical trial.

Melanoma Skin Cancer In Situ (stage 0)

Melanoma skin cancer in situ is also called stage 0 melanoma skin cancer. This means there are cancer cells only in the top layer of skin (the epidermis). Surgery is the main treatment for melanoma in situ. What is an in situ cancer? Some doctors call in situ cancers pre cancer. In a way, they are. Although the cells are cancerous, they cannot spread to other parts of the body, so in situ cancers are not a cancer in the true sense. But if they are not treated, in situ cancers can develop into invasive cancer. What is melanoma in situ? Melanoma skin cancer starts in cells called melanocytes. Melanoma in situ means the cancer cells are all contained in the epidermis where they started. They have not grown deeper into the skin. Stage 0 is part of the number staging system. This goes from stage 0 to stage 4. It tells you how thick the melanoma is and if the cancer cells have spread to the lymph nodes or other parts of your body. Your doctor might also use the TNM staging system for melanoma skin cancer. TNM stages Doctors also use another staging system for melanoma called the TNM staging system. It stands for Tumour, Node, Metastasis. T describes the size of the tumour N describes whether there are any cancer cells in the lymph nodes M describes whether the cancer has spread to a different part of the body The TNM staging system describes the cancer in detail. The number staging system puts these details together to give an overall stage. This can be easier to understand. In the TNM staging system melanoma in situ is the same as Tis, N0, M0. Treatment for melanoma in situ The stage of the cancer helps your doctor decide what treatment you need. Treatment also depends on: where the melanoma is your general health and level of fitness Surgery Surgery is the main treatment for melanoma in situ.  After your diagnosis, you usually have an operation to remove 0.5cm or more of healthy tissue around where the melanoma was. This is called a wide local excision.  If your doctor is sure they removed enough tissue, this is all the treatment you need.  Imiquimod cream Surgery can cause scarring and some people may not be well enough to have an operation. Instead of surgery, you might have treatment with a cream called imiquimod. You put imiquimod on the affected area, over a number of weeks. Your doctor, nurse or pharmacist will tell you how long to use it for. You might have another skin biopsy after you have had imiquimod treatment to see if it has worked. Other number stages

Memorial Sloan Kettering Cancer Center

Deborah Schrag, MDAssociate Attending Physician, Department of Epidemiology and Biostatistics,Memorial Sloan Kettering Cancer CenterMay 2007

Problem: Health services researchers and epidemiologists are interested in secular trends in cancer incidence and survival. Analysis of secular trends requires application of consistent staging algorithms across time periods. However, this is made difficult because staging algorithms change over time.

Problem for Colon Cancer Researchers: The most consistent staging algorithm in use by the SEER registries is SEER historic staging system which categorizes patients as local, regional or advanced. The SEER historic staging system has the principal advantage of being recorded consistently across all time periods. Unfortunately, however, the historic staging system is a suboptimal strategy for colon cancer because it does not map easily to the staging schema that is commonly used by clinicians. The system most commonly used today is the AJCC system (now in its 6th edition) which relies on the TNM system.

The problem with SEER historic stage is that it lumps together node negative (Stage II) and node positive (Stage III) colon cancer patients together. This is problematic because clinical trials and practice guidelines support adjuvant chemotherapy for stage III patients but not for stage II patients where the data to support chemotherapy is equivocal. Therefore, distinguishing between these two groups is essential and investigators are dissatisfied with SEER historic stage to describe colon cancer.

Motivation for Constructing AJCC Staging System Across Time Periods: Analyses of secular trends in health care delivery or the study of technology diffusion such as the use of screening colonoscopy requires accurate and reliable information about stage-specific trends in incidence and survival. The desire to consistently stage colon cancer patients from 1970 to the present using a single schema motivated this project.

Unfortunately, AJCC staging was not recorded by the registrars prior to 1988. However, investigators as part of the cancer intervention and surveillance modeling network (CISNET) colorectal group have gone back to construct staging information for those patients who had cancer directed surgery. This is possible because colon cancer staging relies on assessment of regional lymph nodes. Because the number and involvement of nodes has been recorded consistently, the individual components of information can be used to reconstruct AJCC stage for those patients who had definitive surgery. This technical report serves to outline the approach to accomplish this and to remind users of several important points that should be considered in any analyses that rely on these data sets.

i) The AJCC algorithm for CRC has itself changed over time.

ii) The AJCC algorithm is available at http://training.Seer.Cancer.Gov/staging/systems/ajcc/, and the most recent comparison guide is AJCC Cancer Staging Manual, Fifth versus Sixth Edition.

Although the current system in use is the sixth edition. The sixth edition essential subdivides the 5th edition into smaller more refined prognostic groups. The editions of AJCC map neatly from one to the other. In this report, we supply steps for application of the AJCC 5th edition to cohorts from time periods prior to 1988 when AJCC was not recorded. It is important to note that as long as tumor size/depth of invasion, nodal information and metastatasis information are recorded, AJCC staging schema can be followed.

iii) Because of the time delay in reporting statistics (e.G., 2004 data becomes public available in April 2007), AJCC 5th edition is used instead of the latest version (AJCC 6th edition). In addition, the AJCC 6th edition differs primarily in that it adds additional sub-categories (IIIA, IIIB, IIIC)

Methods for Constructing AJCC Stage Prior to 1988: In order to describe long term trends in stage at diagnosis, disease incidence, and cancer survival, CISNET investigators have reviewed SEER historic staging manuals and applied contemporary staging algorithms (AJCC 5th edition) across time. This is possible for colon cancer for patients who have undergone cancer directed surgery. Over 95% of stage I-III colon cancer patients undergo cancer directed surgery. In the absence of apparent metastatic disease (stage IV-advanced) colon cancer staging requires pathologic assessment of regional lymph nodes. Often clinical investigators are interested in defining cohorts of patients with stage II (node negative) and stage III (node positive) and potentially stage I tumors that required surgical excision. Investigators want pathologically staged colon cancer patients. By combining the cancer site specific surgery codes and the staging codes, we have provided investigators with a way to quickly and efficiently identify cohorts of patients who have pathologically staged colorectal cancer. To provide data users with the potential to compare cohorts across time periods, we have used consistent algorithms to apply the AJCC 5 coding schema to patients who were either: 1) not staged by tumor registrars using the AJCC algorithms; 2) staged by AJCC algorithms prior to the 5th edition. This approach enables investigators to look at secular trends in incidence/mortality/survival using a consistent system over time. Investigators are cautioned in using these data and must recognize the approximate nature of these estimates.

v) While colon cancer is quite straightforward, it is imperative for investigators to recognize the complexities related to rectosigmoid and rectal cancer patients. Rectal cancer patients are increasingly treated with preoperative chemotherapy and radiation. As a result, the pathologic stage recorded does not necessarily correspond to the disease severity at diagnosis. Rectosigmoid patients may have cancers that are either above the peritoneal reflection and therefore true colon cancers or below the peritoneal reflection and therefore true rectal cancers. This distinction is not recorded by SEER. For the purpose of these analyses, rectosigmoid cancers are considered with rectal cancers. However, investigators studying rectal cancer should note that some patients with Rectosigmoid (RS) primaries would not clinically be considered to have rectal cancer.

Colon Cancer Staging Variable for SEER Data (1975-2003): A complex user-defined variable was defined to show colorectal cancer rates by AJCC stage, 5th Edition. The variable was created for use with the SEER Limited-Use Data within the SEER*Stat software(software link available soon) in order to apply AJCC 5th Edition stages to colon cases for years when this staging schema was not previously recorded. This will allow investigators to compare cases across time periods using a staging system commonly used in clinical practice.

A SEER*Stat frequency matrix file is provided here to demonstrate how the variable can be used, and how it was created. In the matrix we show malignant colon and rectal cancer by the defined AJCC stage variable, primary site subdivisions, and year of diagnosis within the SEER 17 registries for 1973-2004.

The AJCC stage variable was created by merging several variables in SEER*Stat in order to show statistics by AJCC stages (I, II, III, IV, unstaged) so that colon cancer is staged consistently for all years in the analysis. In order to do so, stage for

1975-1982 was based on a combination of the 13-digit extent of disease fields,

1983-1987 was based on a combination of the 4-digit extent of disease fields,

1988-2003 was based on AJCC stage, 3rd edition.

The following standard SEER variables were used to define the complex variable:

Year of diagnosis;

Site recode with Kaposi and mesothelioma

Expanded EOD(5) - CP57 (1973-1982);

Expanded EOD(7) - CP59 (1973-1982);

Expanded EOD(12) - CP64 (1973-1982);

Expanded EOD(13) - CP65 (1973-1982);

Expanded EOD(10) - CP62 (1973-1982);

SEER historic stage A;

EOD 4 - extent (1983-1987);

EOD 4 - nodes (1983-1987);

AJCC stage 3rd edition (1988-2003);

2-Digit NS EOD part 1 (1973-1982).

How to Use this Variable: The following example demonstrates how this variable can be used.

You must have SEER*Stat and access to the 1973-2004 SEER Limited-Use data to open the file.

If you look at the matrix, you'll notice that:

The frequencies are displayed by AJCC Stage in the column dimension and Year of Diagnosis in the row dimension.

There are no values for stage for the years 1973-74 and 2004. This variable is defined to use for cases diagnosed between 1975-2003.

To view the session information (selections made to define the parameters of the analysis), select Print Preview from the File menu. A summary of the selections, as well as the user-defined variable definitions can be viewed and printed with the frequency table.

To save the user-defined variable for use in your own SEER*Stat sessions:

a. From the Matrix menu in SEER*Stat, select Retrieve Session.B. From the File menu, select Dictionary….C. On the Dictionary window, use the "+" to expand the Merged folder.D. Double-click on the "AJCC stage (Colon, Deb Schrag 1975-03)" variable to open the Edit Merged Variable window.E. Check the Save to Dictionary box and then click OK.F. The variable will be saved for use in other SEER*Stat sessions.

Additional SEER*Stat Selection for Histologies: On the selection tab in SEER*Stat, the selection of Site recode with Kaposi and mesothelioma = 'Colon and Rectum' excludes cancers outside the colon and rectum and also excludes some histologically-based cancers (leukemias, lymphomas, …). See SEER Site recode variable definition for more information. An additional case selection was made on histology to include only those cell types that clinicians may consider to be colorectal cancer. These selections include: Histologic Type ICD-O-3 = 8000-8001,8010,8020,8140,8210-8211,8220-8221,8260-8263,8480-8482,8490.

Definitions of the Variable Groupings

Stage I:({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1975', '1976', '1977', '1978', '1979', '1980', '1981', '1982'AND {Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 1-3AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 0, '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND ({Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = 0OR ({Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Stage.SEER historic stage A} = 'Localized')))OR ({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1983', '1984', '1985', '1986', '1987'AND (({Extent of Disease.EOD 4 - extent (1983-1987)} = 1AND {Extent of Disease.EOD 4 - nodes (1983-1987)} = 0,9)OR ({Extent of Disease.EOD 4 - extent (1983-1987)} = 2AND {Extent of Disease.EOD 4 - nodes (1983-1987)} = 0)))OR ({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1988', '1989', '1990', '1991', '1992', '1993', '1994', '1995', '1996', '1997', '1998','1999', '2000', '2001', '2002', '2003'AND {Stage.AJCC stage 3rd edition (1988-2003)} = 'Stage I')

Stage II:({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1975', '1976', '1977', '1978', '1979', '1980', '1981', '1982'AND (({Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND (({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 4,6-9, '&'AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 0, '-', 'Blank(s)')OR {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 1-9, '&'))OR ({Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Localized'AND (({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 4,6-9, '&'AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 0, '-', 'Blank(s)')OR {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 1-9, '&'OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 5AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = '-', 'Blank(s)')))OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 'Blank(s)'AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.2-Digit NS EOD part 1 (1973-1982)} = 'Regional, direct extension only'AND {Stage.SEER historic stage A} = 'Regional')))OR ({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1983', '1984', '1985', '1986', '1987'AND {Extent of Disease.EOD 4 - extent (1983-1987)} = 4-7AND {Extent of Disease.EOD 4 - nodes (1983-1987)} = 0)OR ({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1988', '1989', '1990', '1991', '1992', '1993', '1994', '1995', '1996', '1997', '1998','1999', '2000', '2001', '2002', '2003'AND {Stage.AJCC stage 3rd edition (1988-2003)} = 'Stage II')

Stage III:({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1975', '1976', '1977', '1978', '1979', '1980', '1981', '1982'AND ((({Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = 1AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0)AND ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 1-9, '&', '-', 'Blank(s)'OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 2-9, '&')))OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 'Blank(s)'AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.2-Digit NS EOD part 1 (1973-1982)} = 'Regional, nodes only', 'Regional, direct extension and nodes'AND {Stage.SEER historic stage A} = 'Regional')))OR ({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1983', '1984', '1985', '1986', '1987'AND {Extent of Disease.EOD 4 - extent (1983-1987)} = 0-7AND {Extent of Disease.EOD 4 - nodes (1983-1987)} = 1,8)OR ({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1988', '1989', '1990', '1991', '1992', '1993', '1994', '1995', '1996', '1997', '1998','1999', '2000', '2001', '2002', '2003'AND {Stage.AJCC stage 3rd edition (1988-2003)} = 'Stage III')

Stage IV:({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1975', '1976', '1977', '1978', '1979', '1980', '1981', '1982'AND (({Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 1AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0, '-', 'Blank(s)')OR {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 1-9, '&'OR {Stage.SEER historic stage A} = 'Distant'))OR ({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1983', '1984', '1985', '1986', '1987'AND ({Extent of Disease.EOD 4 - extent (1983-1987)} = 8OR {Extent of Disease.EOD 4 - nodes (1983-1987)} = 7))OR ({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1988', '1989', '1990', '1991', '1992', '1993', '1994', '1995', '1996', '1997', '1998','1999', '2000', '2001', '2002', '2003'AND {Stage.AJCC stage 3rd edition (1988-2003)} = 'Stage IV')

Unstaged:({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1975', '1976', '1977', '1978', '1979', '1980', '1981', '1982'AND (({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 4,6-9, '&'AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 0, '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Regional')OR ({Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 1-9, '&'AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Regional', 'Unstaged')OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Unstaged')OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Unstaged')OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 5AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Localized')OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 5AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Localized')OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 5AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Regional')OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = 5AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Localized', 'Regional')OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Unstaged')OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 0AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = 0AND {Stage.SEER historic stage A} = 'Unstaged')OR ({Extent of Disease.Expanded EOD(5) - CP57 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(7) - CP59 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(10) - CP62 (1973-1982)} = '-', 'Blank(s)'AND {Extent of Disease.Expanded EOD(12) - CP64 (1973-1982)} = 'Blank(s)'AND {Extent of Disease.Expanded EOD(13) - CP65 (1973-1982)} = '-', 'Blank(s)'AND (({Extent of Disease.2-Digit NS EOD part 1 (1973-1982)} = 'Non-localized, NOS'AND {Stage.SEER historic stage A} = 'Unstaged')OR ({Extent of Disease.2-Digit NS EOD part 1 (1973-1982)} = 'Localized'AND {Stage.SEER historic stage A} = 'Localized')OR ({Extent of Disease.2-Digit NS EOD part 1 (1973-1982)} = 'Unknown', 'Blank(s)'AND {Stage.SEER historic stage A} = 'Unstaged')OR ({Extent of Disease.2-Digit NS EOD part 1 (1973-1982)} = 'Regional, NOS'AND {Stage.SEER historic stage A} = 'Regional')))))OR ({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1983', '1984', '1985', '1986', '1987'AND (({Extent of Disease.EOD 4 - extent (1983-1987)} = 2-7AND {Extent of Disease.EOD 4 - nodes (1983-1987)} = 9)OR ({Extent of Disease.EOD 4 - extent (1983-1987)} = 3AND {Extent of Disease.EOD 4 - nodes (1983-1987)} = 0)OR ({Extent of Disease.EOD 4 - extent (1983-1987)} = 9AND {Extent of Disease.EOD 4 - nodes (1983-1987)} = 0-6,8-9)OR ({Extent of Disease.EOD 4 - extent (1983-1987)} = 1-7,9AND {Extent of Disease.EOD 4 - nodes (1983-1987)} = 5-6)))OR ({Race, Sex, Year Dx, Registry, County.Year of diagnosis} = '1988', '1989', '1990', '1991', '1992', '1993', '1994', '1995', '1996', '1997', '1998','1999', '2000', '2001', '2002', '2003'AND {Stage.AJCC stage 3rd edition (1988-2003)} = 'Unknown')

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