Underwriting cancers: an update

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Underwriting cancersan update

• F. SESTIER, MD, PhD
• NASLAFKIH, MD, PhD
• September 11, 2007

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Objectives

• Better understanding of the pathology reports
• Better understanding of the cancer classification
• Appreciate the prognostic value of the pathologic
  grade of the tumour
• Appreciate the effect on prognosis of the age of
  occurrence of the cancer

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OUTLINES

• Classification of cancers
• Grade of cancer grade and prognosis
• Type of cancer and prognosis
• Age of occurrence and prognosis
• Breast cancer
• Thyroid cancer
• Melanoma
• Hodgkin lymphoma

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OUTLINES

• Classification of cancers
• Grade of cancer grade and prognosis
• Type of cancer and prognosis
• Age of occurrence and prognosis
• Breast cancer
• Thyroid cancer
• Melanoma
• Hodgkin lymphoma

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Staging Systems for cancers
? Specific for each type of cancer ? Often
competing staging systems exist for the same
type ? The universally-accepted staging system is
that of the UICC (International Union against
cancer), which has the same definitions of
individual categories as the AJCC (American
Joint Committee on Cancer). ? Systems of staging
may differ between diseases or specific
manifestations of a disease.
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What is the TNM system?

• The TNM system is one of the most commonly used
  staging systems. This system has been accepted by
  the International Union Against Cancer (UICC) and
  the American Joint Committee on Cancer (AJCC).
• Most medical facilities use the TNM system as
  their main method for cancer reporting. the NCIs
  comprehensive cancer database, also uses the TNM
  system.

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Blood
Lymphoma uses Ann Arbor Staging Hodgkins
disease follows a scale from I-IV and can be
indicated further by an A or B, depending on
whether a patient is asymptomatic or has
symptoms such as fever. It is known as the
"Cotswold System" or "Modified Ann Arbor
Staging System".
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Solid tumors
TNM is by far the most commonly used system, but
it has been adapted for some conditions. Breast
cancer uses TNM Cervical and ovarian cancer
uses "FIGO" (similar to TNM). For premalignant
cervical dysplastic changes, the CIN (Cervical
Intraepithelial Neoplasia) grading system is
used. Colon Cancer originally consisted of
four stages A, B, C, and D (the Dukes staging
system). More recently, colon cancer staging is
indicated either by the original A-D stages or by
TNM.
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Colorectal cancer Stages grouping
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Colorectal CancerMortality Ratio by stage at
diagnosis
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For solid tumors
Kidney cancer uses TNM Cancer of larynx Uses
TNM Liver cancer uses Stages I-IV Lung
cancer uses TNM Melanoma TNM used. Also of
importance are the "Clark level" and "Breslow
depth" which refer to the microscopic depth of
tumor invasion ("Microstaging"). Prostate
cancer outside of US, TNM almost universally
used. Inside US, Jewett-Whitmore sometimes
used. Non-melanoma skin cancer uses TNM.
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Renal Cancer
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• THE TNM system
• ? The extent of the tumor (T),
• ? The extent of spread to the lymph nodes (N),
• ? The presence of metastasis (M).
• A number is added to each letter to indicate the
  size or extent of the tumor and the extent of
  spread.

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• For many cancers, TNM combinations
• correspond to one of five stages.
• Criteria for stages differ for different types of
  
• cancer.
• For example
• Bladder cancer T3 N0 M0 is stage III
• Colon cancer T3 N0 M0 is stage II.

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Primary Tumor (T) TX Primary tumor cannot be
evaluated T0 No evidence of primary tumor Tis
Carcinoma in situ (early cancer that has not
spread to neighboring tissue) T1, T2, T3, T4
Size and/or extent of the primary tumor Regional
Lymph Nodes (N) NX Regional lymph nodes cannot
be evaluated N0 No regional lymph node
involvement (no cancer found in the lymph nodes)
N1, N2, N3 Involvement of regional lymph nodes
(number and/or extent of spread Distant
Metastasis (M) MX Distant metastasis cannot be
evaluated M0 No distant metastasis (cancer has
not spread to other parts of the body) M1
Distant metastasis (cancer has spread to distant
parts of the body)
)
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Many cancer registries, such as the NCIs
Surveillance, Epidemiology, and End Results
Program (SEER), use Summary Staging. This system
is used for all types of cancer. It groups cancer
cases into five main categories ? In situ
early cancer that is present only in the layer of
cells in which it began. ? Localized cancer
limited to the organ in which it began, without
evidence of spread. ? Regional cancer that
has spread beyond the original (primary) site to
nearby lymph nodes or organs and tissues. ?
Distant cancer that has spread from the primary
site to distant organs or distant lymph nodes.
? Unknown is used to describe cases for which
there is not enough information to indicate a
stage.
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Renal Cancer Stages SEER and prognosis
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OUTLINES

• Classification of cancers
• Grade of cancer grade and prognosis
• Type of cancer and prognosis
• Age of occurrence and prognosis
• Breast cancer
• Thyroid cancer
• Melanoma
• Hodgkin lymphoma

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Grade vs. stage
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Tumor grade

• Tumor grade is a system used to classify cancer
  cells in terms of how abnormal they look under a
  microscope and how quickly the tumor is likely to
  grow and spread.
• The specific factors used to determine tumor
  grade vary with each type of cancer.

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Tumor grade (2)

• Histologic grade, also called differentiation,
  refers to how much the tumor cells resemble
  normal cells of the same tissue type.
• Nuclear grade refers to the size and shape of
  the nucleus in tumor cells and the percentage of
  tumor cells that are dividing.

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Tumor grade (3)

• The cells of Grade 1 tumors resemble normal
  cells, and tend to grow and multiply slowly.
  Grade 1 tumors are generally considered the least
  aggressive in behavior.
• Conversely, the cells of Grade 3 or Grade 4
  tumors do not look like normal cells of the same
  type. Grade 3 and 4 tumors tend to grow rapidly
  and spread faster than tumors with a lower grade.
  

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Tumor grade (4)

• The AJCC recommends the following guidelines for
  grading tumors
• Grade
• GX Grade cannot be assessed
  (Undetermined grade)
• G1 Well-differentiated (Low grade)
• G2 Moderately differentiated
  (Intermediate grade)
• G3 Poorly differentiated (High grade) G4
  Undifferentiated (High grade)

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Lung cancer

• Grade 2
• Grade 3
• Grade 3

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Breast cancer Overall survival as function of
histological grade
Volpi et al. Moderne Pathology 2004 17 1038-1044
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Renal Cancer
Survival by Fuhrman grade J.F. Poisson et coll.,
Progrès en Urologie (2005), 15, 1056-1061
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Renal Cancer
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OUTLINES

• Classification of cancers
• Grade of cancer grade and prognosis
• Type of cancer and prognosis
• Age of occurrence and prognosis
• Breast cancer
• Thyroid cancer
• Melanoma
• Hodgkin lymphoma

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Prognostic Deaths/New cases
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OUTLINES

• Classification of cancers
• Grade of cancer grade and prognosis
• Type of cancer and prognosis
• Age of occurrence and prognosis
• Breast cancer
• Thyroid cancer
• Melanoma
• Hodgkin lymphoma

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Age at diagnosis and prognosis

• Cancer in the young are more aggressive and less
  differentiated
• Cancer in the elderly is associated with less
  screening and tend to be undertreated

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OUTLINES

• Classification of cancers
• Grade of cancer grade and prognosis
• Type of cancer and prognosis
• Age of occurrence and prognosis
• Breast cancer
• Thyroid cancer
• Melanoma
• Hodgkin lymphoma

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Breast cancer
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Breast cancer SEER and AJCC stages grouping
Adapted from Taylor et al. Cancer 2006
106 559-565)
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Breast cancer Relative Risk of death according
to stage
From Gil et al. The Breast 2004 1315-22
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Breast cancer stage I  Mortality analysis
according to age and grade
Adapted from  Henson et al. Cancer 2003
98908-917
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Breast cancer stage II  Mortality analysis
according to age and grade
Adapted from  Henson et al. Cancer 2003
98908-917
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Breast cancer stage III  Mortality analysis
according to age and grade
Adapted from  Henson et al. Cancer 2003
98908-917
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Breast cancer in the elderly
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Breast cancer Long-term mortality according to
stage (Chicago cancer registry) 1547 patients,
mean age 54 years, operated from 1945 -1987)
Stage I (T1 N0 M0) (321 Patients)
Adapted from Karrisson et al. JNCI 1999 9180-85
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(Chicago cancer registry)
Stage IIA (T0 N1 M0, T1 N1 M0, T2 N0 M0) (500
Patients)
Adapted from Karrisson et al. JNCI 1999 9180-85
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Stage IIB (T1 N1 M0, T3 N0 M0) (408 Patients)
(Chicago cancer registry)
Adapted from Karrisson et al. JNCI 1999 9180-85
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Stage III (T0-2 N2 M0 / T3 N1-2 M0 / T4 N0-2 M0
/ T0-4 N3 M0) (318 Patients)
(Chicago cancer registry)
Adapted from Karrisson et al. JNCI 1999 9180-85
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Breast cancer Survival curves according to stage
Byung Ho Son et al. Arch Surg 2006 141 155-160
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Breast cancer Overall survival as function of
histological grade
Volpi et al. Moderne Pathology 2004 17 1038-1044
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Breast cancer 5-years Survival in stages I, IIA
Expected survival (US 1998, female) 0.9425
Adapted from CHIS study 16 No 123, Dec. 2000
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Breast cancerSurvival by stage (SEER) Localized
CA Cancer J Clin 2003 53342-355
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Breast cancer Survival by stage (SEER) Regional
CA Cancer J Clin 2003 53342-355
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Breast cancer Survival by stage (SEER) Distant
CA Cancer J Clin 2003 53342-355
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Breast carcinoma
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OUTLINES

• Classification of cancers
• Grade of cancer grade and prognosis
• Type of cancer and prognosis
• Age of occurrence and prognosis
• Breast cancer
• Thyroid cancer
• Melanoma
• Hodgkin lymphoma

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Thyroid cancer
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T1  1cm T2  1 4cm T3 gt 4cm T4  extra
thyroid
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Mortality Ratio by stage according to
histologic type of thyroid carcinoma
Adapted from Hundahl et al. Cancer 1998
832638-2648
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Thyroid Cancers Relative survival by histologic
type
Source Hundahl et al. Cancer 1998 832638-2648
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Thyroid Cancer Papillary Carcinoma Relative
survival by AJCC stages Source Hundahl et al.
Cancer 1998 832638-2648
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Thyroid Cancer Follicular Carcinoma Relative
survival by stages AJCC Source Hundahl et al.
Cancer 1998 832638-2648
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Thyroid Cancer Medullary Carcinoma Relative
survival by AJCC stage
Source Hundahl et al. Cancer 1998 832638-2648
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Thyroid cancer , case 1

• Aug. 2007 100K, life, 38 yo male, non smoker
• Thyroid, papillary cancer , T2N0M0
• Very well differentiated (Grade 1)
• Margins are free 1.2cm
• Total thyroidectomy, Sept 2004
• Radio-active iodine Oct. 2004
• Normal scan June 2006
• No recurrence, last visit, April 2007

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Manual-Optimum
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Mortality Ratio by stage according to
histologic type of thyroid carcinoma
Adapted from Hundahl et al. Cancer 1998
832638-2648
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Thyroid cancer , case 2

• Sept 2007, 300K , life, 27 yo female, non smoker
• Left thyroidectomy, Jan. 2007
• Papillary tumor, .8cm, margin free, T1N0M0
• May 2007 no recurrence

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Manual-Optimum
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Non-Hodgkin Lymphoma
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Non Hodgkin Lymphoma (NHL)
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Stages of NHL Ann Arbor Staging System

• I 1 L.N. site (or one extra nodal site, IE)
• II 2 or more L.N. sites (same side of
  diaphragm)
• III Involvement above and below diaphragm
• IV Diffuse or disseminated involvement of 1 or
  more
• extra lymphatic tissues or organs
• A Absence of systemic symptoms,
• B Presence of B symptoms

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NHL Ann Arbor Staging System

• Suffix A means absence of B symptoms
• Suffix B means presence of B symptoms
• Suffix E means extra nodal disease
• Suffix S means splenic involvement
• Suffix X means bulky disease
• For example Stage IIIB-S means disease above and
  below the
• diaphragm, with B symptoms and Splenic
  involvement

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NHL Two Commonest subtypes

• Diffuse Large Cell Lymphoma
• Follicular Lymphoma

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Diffuse Large Cell NHLInternational Prognostic
Index

• 5 risk factors should be identified in each
  patient.
• Age gt60
• LDHgt normal
• ECOG performance status 2-4
• Stage III or IV
• Two or more extra nodal sites
• Score/risk category 5 yr survival
• Score 0-1 low risk 73
• Score 2 Low Intermed 51
• Score 3 High Intermed 43
• Score 4-5 High risk 26

Shipp et al Blood 1994831165
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NHL-Lymphoma and survival
Krol et al. Leukemia Lymphoma 2003
44(3)451-458.
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Low grades (follicular NHL)
Survival curve in NHL-follicular compared with
the general population
Krol et al. Leukemia Lymphoma 2003
44(3)451-458.
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High grades (Diffuse Large Cell NHL)
Krol et al. Leukemia Lymphoma 2003
44(3)451-458.
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Diffuse Large B Cell NHL Mortality Ratio by
stages Ann Arbor
Adapted from The International Non-Hodgkin's
Lymphoma Prognostic Factors Project. NEJM 1993
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Hodgkins Disease
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Hodgkins LymphomasHistologic types
1- Lymphocyte predominance 2- Nodular
sclerosis 3- Mixed cellularity 4- Lymphocyte
depletion
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Mortality Ratio according to histologic
morphology (SEER and EUROCARE registries)
Adapted from Allemani et al. Cancer 2006
107 352-360. (Hodgkin disease survival in
Europe and the U.S. Prognostic significance of
morphologic groups)
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Hodgkin lymphoma Staging system
Ann Arbor staging system (idem NHL)
Stage I 1 L.N. site (or one extra nodal site,
IE) Stage II 2 or more L.N. sites (same side of
diaphragm) Stage III Involvement above and below
diaphragm Stage IV Diffuse or disseminated
involvement of 1 or more
extra lymphatic tissues or organs A Absence of
systemic symptoms, B Presence of B
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HodgkinPrognostic factors
Worse prognosis

• Age 45 years worse prognosis
• Stage IV disease
• Hemoglobine lt 10.5 g/dl
• Lymphocytes lt 600/mm3 ou lt 8
• Male sex
• Serum Albumin lt 4.0 g/dl
• White-cell countgt 15,000/mm3

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Hodgkins disease Early stages I-II
Adapted from Ng et al. J Clin Oncol 2002
202101-2108
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Hodgkins disease Advanced stages III-IV
The European Organization for Research and
Treatment of Cancer Lymphoma Group. NEJM
20033482396-2406
739 patients , Age (median) 33 years Hodgkin
lymphoma Stage III, IV (1988-2000) MR 1525
at 10 years Life table France 1990-1999, total
population
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Hodgkins disease Comparison of the long-term
mortality in Hodgkins disease patients with
that of the general population From Provencio et
al. Ann Oncol 1999 101199-1205
From Provencio et al. Ann Oncol 1999
101199-1205
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Hodgkins disease Mortality Ratio By age groups,
stages, follow-up, and period of diagnosis
Adapted from Provencio et al. Ann Oncol 1999
10 1199-1205