Extracting Tumor Stage Information

Overview

The Union for International Cancer Control (UICC) has developed a system for classifying malignant tumors called the TNM staging system. Each tumor is assigned an alphanumeric code (the TNM code) that describes the extent of the tumor, lymph node involvement, whether it has metastasized, and several other descriptive factors. The code also includes staging information. ClarityNLP can locate these codes in medical reports and decode them. This document describes the TNM system and the information that ClarityNLP provides for each TNM code that it recognizes.

Information on the TNM system was taken from the reference document [1] and the explanatory supplement [2]. Information on serum marker values was taken from the Wikipedia article on the TNM staging system [3].

Source Code

The source code for the TNM stage module is located in nlp/algorithms/value_extraction/tnm_stage_extractor.py.

Inputs

A single string representing the sentence to be searched for TNM codes.

Outputs

A JSON array containing these fields for each code found:

Field Name	Explanation
text	text of the complete code
start	offset of first char in the matching text
end	offset of final char in the matching text + 1
t_prefix	see prefix code table below
t_code	extent of primary tumor
t_certainty	primary tumor certainty factor
t_suffixes	see T suffix table below
t_multiplicity	tumor multiplicity value
n_prefix	see prefix code table below
n_code	regional lymph node involvement
n_certainty	certainty factor for lymph node involvement
n_suffixes	see N suffix table below
n_regional_nodes_examined	number of regional lymph nodes examined
n_regional_nodes_involved	number of regional lymph nodes involved
m_prefix	see prefix code table below
m_code	distant metastasis
m_certainty	certainty factor for distant metastasis
m_suffixes	see M suffix table below
l_code	lymphatic invasion code
g_code	histopathological grading code
v_code	venous invasion code
pn_code	perineural invasion code
serum_code	serum tumor marker code
r_codes	residual metastases code
r_suffixes	see R suffix table below
r_locations	string array indicating location(s) of metastases
stage_prefix	see prefix table below
stage_number	integer value of numeric stage
stage_letter	supplementary staging information

All JSON measurement results contain an indentical number of fields. Any fields that are not valid for a given measurement will have a value of EMPTY_FIELD and should be ignored.

Algorithm

ClarityNLP uses a set of regular expressions to recognize TNM codes as a whole and to decode the individual subgroups. A TNM code consists of mandatory T, N, and M groups, as well as optional G, L, R, Pn, S, and V groups. A staging designation may also be present.

Prefixes

The set of prefixes used for the groups is found in the next table:

Prefix Letter	Meaning
c	clinical classification
p	pathological classification
yc	clinical classification performed during multimodal therapy
yp	pathological classification performed during multimodal therapy
r	recurrent tumor
rp	recurrence after a disease-free interval, designated at autopsy
a	classification determined at autopsy

Certainty Factor

The T, N, and M groups can have an optional certainty factor, which indicates the degree of confidence in the designation. This certainty factor was present in the 4th through 7th editions of the TNM guide, but it has been removed from the 8th edition [1].

Certainty Factor	Meaning
C1	evidence from standard diagnostic means (inspection, palpitation)
C2	evidence from special diagnostic means (CT, MRI, ultrasound)
C3	evidence from surgical exploration, including biopsy and cytology
C4	evidence from definitive surgery and pathological examination
C5	evidence from autopsy

T Group

The T group describes the extent of the primary tumor:

T Code	Meaning
TX	primary tumor cannot be assessed
T0	no evidence of primary tumor
Tis	carcinoma in situ
T1, T2, T3, T4	increasing size and/or local extent of primary tumor

For multiple tumors, the multiplicity appears in parentheses after the T group code, e.g. T1(m) or T1(3). Anatomical subsites are denoted with suffixes a, b, c, or d, e.g. T2a. Recurrence in the area of a primary tumor is denoted with the + suffix.

N Group

The N group describes the extent of regional lymph node involvement:

N Code	Meaning
NX	reginal lymph node involvement cannot be assessed
N0	no regional lymph node metastasis
N1, N2, N3	increasing involvement of regional lymph nodes

Anatomical subsites are denoted with suffixes a, b, c, or d, e.g. N1b. With only micrometastasis (smaller than 0.2 cm), the suffix (mi) should be used, e.g. pN1(mi).

Suffix (sn) indicates sentinal lymph node involvement.

Examination for isolated tumor cells (ITC) is indicated with the suffixes in parentheses (e.g. pN0(i-)):

ITC Suffix	Meaning
(i-)	no histologic regional node matastasis, negative morphological findings for ITC
(i+)	no histologic regional node metastasis, positive morphological findings for ITC
(mol-)	no histologic regional node metastasis, negative non-morphological findings for ITC
(mol+)	no histologic regional node metastasis, positive non-morphological findings for ITC

Examination for ITC in sentinel lymph nodes uses these suffixes:

ITC(sn) Suffix	Meaning
(i-)(sn)	no histologic sentinel node matastasis, negative morphological findings for ITC
(i+)(sn)	no histologic sentinel node metastasis, positive morphological findings for ITC
(mol-)(sn)	no histologic sentinel node metastasis, negative non-morphological findings for ITC
(mol+)(sn)	no histologic sentinel node metastasis, positive non-morphological findings for ITC

The TNM supplement [2] chapter 1, p. 8 recommends adding the number of involved and examined regional lymph nodes to the pN classification (pathological classification), e.g. pN1b(2/11). This example says that 11 regional lymph nodes were examined and two were found to be involved.

M Group

The M group describes the extent of distant metastasis:

M Code	Meaning
MX	metastasis cannot be assessed; considered inappropriate if metastasis can be evaluated based on physical exam alone; see [1] p. 24, [2] pp. 10-11.
M0	no distant metastasis
M1	distant metastasis
pMX	invalid category ([2], p. 10)
pM0	only to be used after autopsy ([2], p. 10)
pM1	distant metastasis microscopically confirmed

The M1 and pM1 subcategories may be extended by these optional suffixes, indicating the location of the distant metastasis:

Location Suffix	Meaning
PUL	pulmonary
OSS	osseous
HEP	hepatic
BRA	brain
LYM	lymph nodes
MAR	bone marrow
PLE	pleura
PER	peritoneum
ADR	adrenals
SKI	skin
OTH	other

Anatomical subsites are denoted with suffixes a, b, c, and d. The suffix (cy+) is valid for M1 codes under certain conditions (see [2] p. 11).

For isolated tumor cells (ITC) found in bone marrow ([2] p. 11), these suffixes can be used:

Suffix	Meaning
(i+)	positive morphological findings for ITC
(mol+)	positive non-morphological findings for ITC

R Group

The R group describes the extent of residual metastases:

R Code	Meaning
RX	presence of residual tumor cannot be assessed
R0 (location)	residual tumor cannot be detected by any diagnostic means
R1 (location)	microscopic residual tumor at indicated location
R2 (location)	macroscopic residual tumor at indicated location

The TNM supplement ([2], p. 14) recommends annotating R with the location in parentheses, e.g. R1 (liver). There can also be multiple R designations if residual tumors exist in more than one location.

The presence of noninvasive carcinoma at the resection margin should be indicated by the suffix (is) (see [2], p. 15).

The suffix (cy+) for R1 is valid under certain conditions ([2], p. 16).

G Group

The G group discribes the histopathological grading score and has these values:

G Code	Meaning
GX	grade of differentiation cannot be assessed
G1	well differentiated
G2	moderately differentiated
G3	poorly differentiated
G4	undifferentiated

G1 and G2 may be grouped together as G1-2 ([2], p. 23).

G3 and G4 may be grouped together as G3-4 ([2], p. 23).

L Group

The L group indicates whether lymphatic invasion has occurred:

L Code	Meaning
LX	lymphatic invasion cannot be assessed
L0	no lymphatic invasion
L1	lymphatic invasion

V Group

The V group indicates whether venous invasion has occurred:

V Code	Meaning
VX	venous invasion cannot be assessed
V0	no venous invasion
V1	microscopic venous invasion
V2	macroscopic venous invasion

Pn Group

The Pn group indicates whether perineural invasion has occurred:

Pn Code	Meaning
PnX	perineural invasion cannot be assessed
Pn0	no perinerual invasion
Pn1	perineural invasion

Serum Group

The S group indicates the status of serum tumor markers:

S Code	Meaning
SX	marker studies not available or not performed
S0	marker study levels within normal limits
S1	markers are slightly raised
S2	markers are moderately raised
S3	markers are very high

Staging

The staging value indicates the severity of the tumor. A staging assignment depends on the tumor type and is indicated either with digits or roman numerals, and optionally with subscript a, b, c, or d. The stage designation can also have a y or yp prefix as well ([2], p. 18).

References

[1]	(1, 2, 3) J. Brierly, M. Gospodarowicz, C. Wittekind, eds. TNM Classification of Malignant Tumors, Eighth Edition Union for International Cancer Control (UICC) Wiley Blackwell, 2017 https://www.uicc.org/resources/tnm

[2]	(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) C. Wittekind, C. Compton, J. Brierly, L. Sobin, eds. TNM Supplement: A Commentary on Uniform Use Union for International Cancer Control (UICC) Wiley Blackwell, 2012

[3]	https://en.wikipedia.org/wiki/TNM_staging_system