Systemic Treatment for Multiple Primary Cancers

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Systemic Treatment for Multiple Primary Cancers

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Title: Systemic Treatment for Multiple Primary Cancers

1
Systemic Treatment for Multiple Primary Cancers
Arizona Cancer Registry
2
Why a Module on This Topic?

Occasionally, a patient will be diagnosed
concurrently with multiple primaries, and receive
systemic treatment for all of these malignancies.
This does not happen frequently, but when it does
it can be a source of confusion.
The questions for the registrar are
How do you know which treatments are directed at
which cancer?
What and where are the rules addressing these
scenarios?

3
First, a Few Definitions

Concurrent
Simply, happening at the same time
Multiple Primaries
Generally, primaries are separate if you have
Multiple lesions with the same histology
occurring in different sites, unless a physician
states that one is metastatic from the other
Multiple lesions with different histologies
occurring in different sites
Multiple lesions with different histologies
occurring in the same site
The issue of what constitutes multiple
primaries is discussed extensively in FORDS
Revised for 2004, pages 15-20. The three
definitions given above are most relevant to this
discussion.

4
Definitions, Continued

Systemic Therapy
Any treatment that circulates through the
bloodstream is considered to be systemic,
reaching and affecting cells all over the body.
An extensive discussion of systemic therapy can
be found in FORDS Revised for 2004, pages 28F
and 28G.

5
Types of Systemic Therapy

Systemic treatments of the same type, e.g.,
chemotherapy, hormonal therapy, and immunotherapy
can act on different targets.
Chemotherapy
Hormonal Therapy
Immunotherapy
Radioisotopes- In rare cases
Radioisotopes are usually cell-specific and
therefore have particular targets.
Endocrine therapy
Orchiectomy for advanced prostate cancer
Prophylactic oophorectomy for breast cancer
Hematologic transplants

6
Therapy Not Considered Systemic

Radiation
Surgery
Topical antineoplastics
Drugs that are applied to the surface of the
body, often for treatment of skin lesions
The common denominator of these treatment types
is that they are intended for local control of
disease.

7
Radiosensitizers

Radiosensitizers are drugs that make cells more
sensitive to the effects of radiation
Examples include 5-FU, Broxuridine
Radiosensitizers are NOT coded as chemotherapy
---
They are used for the purpose of enhancing
radiation treatment
They are listed as ancillary agents in the
SEERRx database

Next, a brief discussion of the major types of
systemic therapies

9
Chemotherapy

Causes cells to stop growing or to die by
interrupting DNA synthesis and replication.
Alkylating agents such as Cytoxan and Leukeran
interfere with DNA replication.
Antimetabolites change the function of enzymes
used in cell metabolism and protein synthesis.
Examples of antimetabolites include 5-FU and
methotrexate.
Antitumor antibiotics interfere with nucleic acid
(building blocks of DNA) synthesis. Adriamycin
(Doxorubicin) and bleomycin are two antitumor
antibiotics.
Alkaloids target the spindle proteins necessary
for cell division, inhibiting mitosis. Examples
include vincristine and vinblastine.

10
Hormone Therapy Definition and Types

Hormone Therapy
Seeks to slow or stop the proliferation of cancer
cells that are dependent on hormonal action to
grow.
Major types of hormonal therapy
Hormone-releasing factors
Hormones
Antihormones
Selective Estrogen Receptor Modulators (SERMs)
Aromatase Inhibitors

11
Hormone-Releasing Factors

Hormone-releasing factors influence production of
specific hormones via a feedback loop.
e.g., Luteinizing-releasing hormone (LHRH) in
the hypothalamus controls release of
follicle-stimulating hormone and luteinizing
hormone (LH) from the pituitary.
Agonists mimic the action of hormone-releasing
factors.
For instance, if a male receives chronic high
doses of LHRH agonists, this results in
decreased androgen levels by interfering with
the production or action of LHRH or LH via the
feedback loop.
e.g. Lupron and Zoladex

12
Hormones, Antihormones, and SERMs

Hormones- Androgens, estrogens, progestins,
corticosteroids
Used to oppose the activity of other
cancer-fueling hormones
e.g., Androgens can be used to counteract
estrogens and slow the growth of an
estrogen-dependent cancer (e.g.,
fluoxymesterone).
e.g., Prednisone is a corticosteroid.
Antihormones- Antiestrogens, antiandrogens,
adrenal steroid inhibitors
Erect a chemical barrier between the hormone
and its receptor on a cells surface
e.g. Tamoxifen, Casodex
Selective Estrogen Receptor Modulators (SERMs)
Act like estrogen in some organs and like an
anti-estrogen in others
e.g., Raloxifene

13
Aromatase Inhibitors

Aromatase is an enzyme that converts androgens,
produced by the adrenal glands, into estrogens.
Aromatase inhibitors block this conversion,
resulting in decreased estrogen levels and slowed
growth of estrogen-dependent tumors.
e.g., Armidex

14
Biologic Therapy Definition and Types

Manipulates immune system to target and/or
destroy cancer cells also known as
immunotherapy.
Two basic types
Active immunotherapy Boosts the patients
existing defenses immunization of patient with
materials to elicit an immune reaction against
the tumor. May be
Specific- Targets antigens on specific type of
cancer cell
Non-specific- Elicits a more general immune
response
Passive immunotherapy Sometimes called adoptive
immunotherapy gives the patient antibodies and
other agents so that the patient adopts an immune
response that has been developed in a test tube.

15
Active Immunotherapy Interferons

Naturally-occurring proteins that interfere with
virus replication (hence the name interferon.)
Able to be used against cancer because of
advances in recombinant DNA technology.
Mechanisms of action include
Enhancing antigens so that antibodies can seek
out cancer cells more effectively
Inhibiting DNA and protein synthesis
e.g. Interferon alpha-2b is used against
Kaposis sarcoma, hairy cell leukemia, follicular
lymphoma and malignant melanoma.

16
Active Immunotherapy Interleukins

Proteins produced by leukocytes, monocytes, and
other cells that regulate immune response
Work by boosting number and activity of
lymphocytes, especially killer T-cells.
e.g.,Interleukin-2 is used for metastatic renal
cell carcinoma.

17
Passive Immunotherapy Monoclonal Antibodies

Administered to the patient, as opposed to active
immunotherapy which seeks to boost already
existing defenses
Monoclonal antibodies- Lab-engineered products.
Work by
Attaching to specific antigen sites on tumor
cells to interfere with their growth and
replication, OR
Marking cell for destruction by immune system
Two basic types
Naked- Used alone
Conjugated- Used in combination with other drugs,
toxins, or radioactive substances the monoclonal
antibody delivers the agent to the cell by
identifying and tagging the antigen.
e.g. Rituxan for B-cell lymphoma, Herceptin for
breast cancer

18
Endocrine Therapy

Utilizes surgery or radiation to remove source of
hormones, which secondarily slows the growth of
tumor by starving it of the hormones it needs to
grow.
E.g., Orchiectomy for advanced prostate cancer,
oophorectomy for breast cancer
Endocrine therapy is not coded as hormonal
therapy.
Endocrine therapy is coded in the field
Hematologic Transplant and Endocrine Procedures

19
Hematologic Transplants

Bone marrow or stem cell transplants performed
to protect patients from myelosuppression or bone
marrow ablation associated with administration of
high-dose chemotherapy or radiation. (FORDS
Revised for 2004, p. 28F).
Stem cells are immature forms that have the
potential to differentiate into WBC, RBCs, or
platelets.
Types of hematologic transplants
Autologous bone marrow- Uses cells harvested from
the patient, stored, and then infused back into
the patient after high-dose chemo or radiation
Allogenic bone marrow- Uses cells harvested from
a donor
Syngeneic bone marrow- Uses cells harvested from
identical twin
Peripheral blood- Stem cells come from
bloodstream as opposed to bone marrow
Like Endocrine Procedures, Hematologic
Transplants are coded in the Hematologic
Transplant and Endocrine Procedures item.

20
ABSTRACTING CODING ISSUES
21
Why these therapies can pose a challenge for the
registrar

Unlike surgery and radiation therapy, the
systemic therapies just described have the
potential to impact a number of different
tissues.
For this reason, you need to ask yourself two
questions when coding therapy for multiple
primaries
How do you determine which systemic treatment is
directed at which primary?
The bottom-line question then becomes Which
agent has the potential to impact which primary?

22
Where Do You Find Info to Answer These Questions?

There are a large number of resources available
on the World Wide Web.
Two of the more comprehensive sites include
SEERRx- Should be the first source you look to
National Cancer Institute
SEERRx and the NCI web site will be discussed in
some detail here.

23
Additional Guidance is Provided In

SEER Program Coding and Staging Manual 2004 (p.
172) states
If a patient has multiple primaries and the
treatment given for one primary also
affects/treats the other primary, code the
treatment for both primary sites.

24
Introducing SEERRx

Released July, 2005
Must be used in place of SEER Book 8,
Antineoplastic Drugs, and its supplements for
cases diagnosed 1/1/2005 and after.

25
How to Download SEERRx

Go to http//www.seer.cancer.gov/tools/seerrx/
Request a password using the online form.
After your user name and password are emailed to
you, you can install the program by following the
onscreen instructions.

26
Using SEERRx

Each entry contains information on
Generic name
Category (Chemotherapy, Hormone therapy, etc.)
Brand name
Subcategory
Antiangiogenic agent, antiestrogen are two
examples
This field is useful for determining the family
of drugs that an agent belongs to.
Abbreviations
Primary Sites

27
More on Using SEERRx

When you are coding treatment, the most relevant
information will be found in the following
sections
Generic Name
Brand Name
Sometimes a clinician will refer to a drug by one
of several names
Category
Chemotherapy, Hormones and hormonal mechanisms
Biologic Therapy, etc.
Useful for coding purposes
Primary Sites
Malignancies the agent is used for
Remarks
Miscellaneous info, including indicated usages,
FDA-approved, off-label, and clinical trials
Refer to slide 29, Notes of Caution, for
additional info.

28
Using SEERRx, continued

Remember
If a chemotherapy drug that a patient is
receiving is changed to another drug in the same
family, it would not be considered subsequent
treatment. However, if the new drug comes from a
different category, then it would be considered
subsequent treatment.
For example, a switch to Carboplatin from
Cisplatin would not be considered subsequent
treatment, since they are both alkylating agents
and in the same subcategory of Miscellaneous
agent in SEERRx
Code only the original agent (first course).
(Reference FORDS Revised for 2004, pages
28F-28G).

29
Notes of Caution
.

SEERRx is subject to update as more current
therapy information becomes available.
SEERRx is not exhaustive. If a site is not
listed, it is still possible that the drug is
being used to treat the cancer.
A patient can be treated off-label or
off-protocol, which usually implies that the
drug is not being used routinely for a particular
disease, but that the drug may have shown some
efficacy in clinical trials and therefore may
have some effect on the cancer.
If you find only one of the primary sites for the
case you are abstracting, it is a good idea to do
additional research. If the site is not listed in
the entry for a drug, and you find when you look
further that the drug can be used as treatment
for the site/histology in question, code as
appropriate.

30
More Notes of Caution

Do not consider treatment dates when trying to
decide if SEERRx is an appropriate reference.
Only consider the diagnosis date (1/1/2005 and
later ).
Also, spelling needs to be correct. For instance,
if you enter Tamoxifan it wont bring up
Tamoxifen (the right spelling).
Alternatively, entering the first few letters of
an agents name will bring up entries, e.g.,
Tamox.

31
National Cancer Institutehttp//www.cancer.gov

Web site contains a subsection with information
about the treatments for all cancers. This
subsection includes
General info about site/histology
Broad overview of therapies
Summaries of standard treatment options, as well
as those under evaluation, according to stage
References

32
To Get There

http//www.cancer.gov
The Types of Cancer section in the middle of
the page contains two links
Common Cancer Types
All Cancer Types
A to Z list of sites/histologies, including those
listed under Common Cancer Types
Select the primary site

33
To Get There, continued

Selecting a link for the primary site will bring
up a page containing a number of subsections,
each with its own links.
Under the first option, Treatment, (Located in
the center of the page), will be links for
patients and health professionals. Follow the
health professional link.

34
Navigating the Treatment Section of the NCI web
site

The left side of the Treatment page has a list of
options, including
General Information
Cellular Classification
Stage Information
Treatment Option Overview
Stages
Discussion of therapy options by stage
Recurrent
Management of recurrences/progression
Changes to Summary (Date)
Updates as new information becomes available
More Information
Links to specific topics on the NCI web site,
such as prevention, genetics, supportive care,
etc.
The most useful links will be Treatment Option
Overview and the individual stages.

35
To Summarize Some Treatment Information Issues

It may be worth your while to check these
references first
http//seer.cancer.gov/tools/seerrx
http//www.cancer.gov/
Another option, if the above two references dont
give you any answers, is to search on the agents
nameManufacturers usually have a website that
may contain helpful information.
Warning Manufacturers websites may not use
the same terminology as the registrars
websites. For instance, a manufacturer may
refer to an agent as immunotherapy, but SEERRx
may categorize it as something else.
Query the treating physician if you cant find
answers using reference sources.

36
Medical Record Documentation

The way treatment is documented in the record is
not necessarily how it is coded by the registrar.
For instance
Ancillary drugs such as Epogen or Zometa are not
coded as cancer-directed therapy, even though
this may be the impression given in the
documentation.

37
Documentation, continued

If a physician states that the patient was given
an agent for one primary,
AND
You find that the drug is also effective against
the second cancer,
THEN
Code the agent for both primaries. In this case,
you may override what the physician states.

38
And Beware

Of the diagnosis given on order sheets.
The diagnosis information recorded on an order
sheet may not be comprehensive enough to use in
coding treatment.
For instance, an order sheet may state that a
chemotherapy regimen is being given for one
primary, when it may in fact be effective against
the other primary (ies) as well. An example given
later in this module (Case 1) illustrates this
point.

39
Agents Also Used for Non-Malignant Conditions

If a patient is undergoing systemic treatment for
a non-malignant condition, and then develops a
cancer, do not code the systemic treatment for
the cancer.
For instance, a patient being treated with
methotrexate for rheumatoid arthritis develops
prostate cancer.
Do not code the methotrexate as treatment for the
prostate cancer.

And Now for a Few Exercises

41
Case 1

Diagnosis
Sequence 01 C41.3, M9231/3, Myxoid
chondrosarcoma of costal cartilage
Sequence 02 C50.5, M8530/3, Inflammatory
carcinoma of breast
Both primaries diagnosed 5/05.
Treatment
6/05 Ifosfamide, Mesna, Adriamycin, Cisplatin,
Mitomycin-C
Diagnosis on order sheets Breast ca. and
sarcoma
8/05 Partial sternectomy w/reconstruction
Modified radical mastectomy
11/05 Doxorubicin, cyclophosphamide
Diagnosis on chemotherapy order sheet
Breast ca.

42
Case 1

Question
Which primary should the Doxorubicin and
Cyclophosphamide, given in 11/05, be coded to?
Breast
Breast and sarcoma
Remember Use your references.
Also, the therapy given in 11/05 would be
considered subsequent therapy, which is not
required to be reported to the Arizona Cancer
Registry (ACR) this is for illustrative purposes
only.

43
Case 1

Answer
B, Breast and sarcoma
Rationale
Doxorubicin (generic for Adriamycin) and
cyclophosphamide are used for both breast
carcinoma and sarcoma per the drugs entries in
the SEERRx database.
Although the order sheet states the treatment is
being given for breast cancer, the registrar in
this case would need to review references to find
out whether Doxorubicin and cyclophosphamide are
also effective for sarcoma.

44
Case 2

Diagnosis
Sequence 01 C50.1 (L), M8522/3, Infiltrating
duct and lobular carcinoma of breast
Sequence 02 C50.5 (R), M8500/3, Infiltrating
duct carcinoma of breast
Both breast primaries were diagnosed in 2/05.
Sequence 03 C44.2, M8720/3, Malignant melanoma
of external ear
Melanoma diagnosed 4/05
Treatment
3/05 Bilateral modified radical mastectomies
4/05 Wide excision of skin lesion
5/05 Aromasin

45
Case 2

Question
Which primary should Aromasin be coded to?
Breast
Melanoma
Breast and melanoma

46
Case 2

Answer
A, Breast
Rationale
Aromasin is a hormone that, per SEERRx, is
active against breast cancer.
Aromasin does not impact melanoma melanoma is
not mentioned anyplace in the SEERRx entry.
Also, the Treatment Option Overview for
melanoma on NCIs web site does not mention
hormonal therapy as having a role in the
treatment of melanoma. Treatment Option
Overview provides a synopsis of the standard and
experimental therapies used for each stage of
disease. The overview was used in this example
because there is no stage information for the
melanoma. If extent of disease is documented,
following the appropriate stage link will give
you more detailed information.

47
Case 3

Diagnosis
Sequence 01 C16.0, M8140/3, Adenocarcinoma of
gastroesophageal junction
Sequence 02 C64.9, M8310/3, Clear cell carcinoma
of kidney
Both primaries were diagnosed in 10/05.
Physician noted that the kidney ca. would be
addressed after treatment for the GE primary, as
the GE junction cancer had a worse prognosis.
Treatment
11/05 Continuous infusion 5-FU
Diagnosis on order sheets Gastroesophageal ca.
11/05 Begins external beam radiation
3/06 Transhiatal esophagogastrectomy and partial
nephrectomy
No change in size of renal mass from date of
diagnosis to
date of resection

48
Case 3

Question
Which primary should 5-FU be coded to?
Gastroesophageal junction
Kidney
Gastroesophageal junction and kidney

49
Case 3

Answer
A, Gastroesophageal junction
Rationale
According to the SEERRx Remarks entry, 5-FU is
approved for use against GI adenocarcinoma.
Other types of cancers are not mentioned. The
Treatment Option Overview in the kidney cancer
section of NCIs web site states that Systemic
therapy has demonstrated only limited
effectiveness.

50
Case 4

Diagnosis
Sequence 01 C42.1, M9823/3, Chronic lymphocytic
leukemia
Sequence 60 C75.1, M8272/0, Pituitary adenoma
Both primaries were diagnosed in 8/05.
Treatment
9/05 Bromocriptine

51
Case 4

Question
Which primary should Bromocriptine be coded to?
Pituitary adenoma
CLL
Pituitary adenoma and CLL

52
Case 4

Answer
A, Pituitary adenoma
Rationale
The hormonal mechanism for bromocriptine is not
the same as for prednisone or other hormonal
treatments for CLL a review of the CLL Treatment
section on NCIs web site does not mention this
particular drug.
The bromocriptine entry in SEERRx does not
mention pituitary adenomas. However, it briefly
states that the drugs mechanism of action is the
inhibition of prolactin secretion from the
pituitary.
Also, an examination of the Treatment Option
Overview for pituitary adenomas on the NCI web
site specifically states that this agent is used
to treat prolactin-secreting pituitary adenomas.
This case would be a good example of the
importance of learning to rely on multiple
sources.

53
Case 5

Diagnosis
Sequence 01 C25.0, M8140/3, Adenocarcinoma of
head of pancreas, Diagnosed 4/05
Sequence 02 C18.4, M8140/3, Adenocarcinoma of
transverse colon, Diagnosed 5/05
Treatment
4/05 Whipple procedure
5/05 External beam radiation to pancreatic tumor
bed
5-FU given as radiosensitizing agent
Gemcitabine treatment continued through 6/05.

54
Case 5

Question
Which primary should the 5-FU and Gemcitabine be
coded to?
Pancreas
Colon
Pancreas and colon

55
Case 5

Answer
A, Pancreas
Rationale
5-FU is sometimes used as a sensitizing agent
when given concurrently with radiation therapy.
5-FU can also be used as chemotherapy, but if
given as a radiosensitizer it is considered an
ancillary drug and NOT coded.
Note If a patient is diagnosed with a new
primary while undergoing first course treatment
for a cancer diagnosed previously, and the
drug(s) used for the initial cancer is/are
potentially effective against the malignancy that
is diagnosed later
Do not include the regimen in planned first
course of treatment, because obviously it had no
effect on the growth of the new primary.
BUT do mention the drug in a text field when you
abstract the subsequent primary.

56
When Do These Guidelines Become Effective?

Coding Systemic Treatments Potentially Effective
for gt 1 Primary Cancer
ACR polled participants from the 10/27/05
teleconference and found that a majority were
already coding according to these guidelines, but
that a significant minority were coding strictly
per the medical record documentation.
Therefore, the guidelines provided in this module
apply to cases diagnosed on or after 1/1/2005.
Registrars who are already coding using the
principles discussed above do not need to go back
to identify and update applicable cases.

57
Identifying Applicable Cases

Cases diagnosed on or after 1/1/2005 must be
reviewed in order to be corrected where
necessary.
Specifics for identifying these cases in your
database will vary somewhat depending on your
software, but these general procedures could be
utilized across the board
Create a subset based on
Diagnosis date
1/1/2005 and later
Sequence number
gt 00
From the subset, create a listing using the
following fields
Name
Medical record number
Sequence number
Diagnosis date
Date first course treatment
Use the info from this listing as a guide in
determining which cases to review.

58
Dont Forget!

If you are making a change to a case that you
already submitted to the ACR, complete a Critical
Change Form and send it to the state
Updates of first course of treatment fields are
considered to be critical changes.

59
In Summary

Some systemic therapies have demonstrated
activity against more than one malignancy.
It is the job of the registrar to determine which
agent(s) is(are) recorded in which abstract(s)
when a patient is being concurrently treated for
two or more cancers.
Fortunately, there are a number of resources that
a registrar can utilize in order to tease out
this info.

60
SEERRx Summarized

SEERRx
Database of agents active against cancer
Went live in July, 2005.
Can be downloaded free of charge with a username
and password obtained from SEER.
Primary sites and Remarks fields will
probably be the most useful when trying to
determine if an agent is useful against a
specific malignancy.
To be updated periodically with knowledge
advances.
Effective for cases diagnosed 1/1/2005 and after
do not take treatment dates into consideration
when determining if you can use SEERRx for a
case.
Just because a cancer is not listed in the drug
entry does NOT mean it isnt being used for that
cancer.

61
NCIs Web Site in a Nutshell

http//www.cancer.gov
Provides an overview of treatment by stage for
all cancer types.
Information more in-depth than that provided in
SEERRx
Web pages are updated as information about
advances becomes available. View updates by
following the Changes to this Summary link at
the bottom of the treatment by AJCC stage
summaries links.

62
And Remember

The ACR must be notified about changes made to
first-course treatment data on cases that have
already been submitted.
Two options for reporting updates
Critical change form- Available on the ACR web
site, http//www.azdhs.gov/phs/phstats/acr/registr
arresources.htm
Print off abstract and highlight changes.

63
A Few More Helpful Resources

TO NAME JUST A HANDFUL
CancerConsultants - http//professional.cancercons
ultants.com
Online resource center for oncology
professionals. Contains links to articles on
treatment advances.
Can sign up for newsletter free of charge
SEERs Training Web Site - http//training.seer.ca
ncer.gov
Site-specific modules contain information on
current treatments, including names of agents.
Information tends to be general.
CA A Journal for Clinicians - http//caonline.amc
ancersoc.org
Published by American Cancer Society
Good source of information about treatments and
advances (along with many other cancer-related
topics)
Free access to full-text articles
American Society of Clinical Oncology (ASCO) -
http//www.asco.org
Society represents oncology physicians
Free access to article abstracts and some
full-text articles

64
AND PERHAPS THE BIGGEST CHALLENGE OF ALL

Given the vast amount of information available on
the web, finding additional sources shouldnt be
difficult.
BUT
What may be a challenge is sifting through the
material and finding quality information
that is relevant, up-to-date and accurate.

65
Questions? Comments? Additions?