Introduction to Cancer Treatment

Overview of Cancer Treatments

Choice of cancer treatment is influenced by several factors, including the specific characteristics of your cancer; your overall condition; and whether the goal of treatment is to cure your cancer, keep your cancer from spreading, or to relieve the symptoms caused by cancer.  Depending on these factors, you may receive one or more of the following:

• Surgery
• Chemotherapy
• Radiation therapy
• Genetic Testing and Personalized Medicine

One or more treatment modalities may be used to provide you with the most effective treatment.  Increasingly, it is common to use several treatment modalities together (concurrently) or in sequence with the goal of preventing recurrence.  This is referred to as multi-modality treatment of the cancer.

Surgery

Surgery is used to diagnose cancer, determine its stage, and to treat cancer. One common type of surgery that may be used to help with diagnosing cancer is a biopsy.  A biopsy involves taking a tissue sample from the suspected cancer for examination by a specialist in a laboratory. A biopsy is often performed in the physician’s office or in an outpatient surgery center. A positive biopsy indicates the presence of cancer; a negative biopsy may indicate that no cancer is present in the sample.

When surgery is used for treatment, the cancer and some tissue adjacent to the cancer are typically removed.  In addition to providing local treatment of the cancer, information gained during surgery is useful in predicting the likelihood of cancer recurrence and whether other treatment modalities will be necessary.

Chemotherapy

Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill. Chemotherapy is different from surgery or radiation therapy in that the cancer-fighting drugs circulate in the blood to parts of the body where the cancer may have spread and can kill or eliminate cancers cells at sites great distances from the original cancer. As a result, chemotherapy is considered a systemic treatment.

More than half of all people diagnosed with cancer receive chemotherapy.  For millions of people who have cancers that respond well to chemotherapy, this approach helps treat their cancer effectively, enabling them to enjoy full, productive lives. Furthermore, many side effects once associated with chemotherapy are now easily prevented or controlled, allowing many people to work, travel, and participate in many of their other normal activities while receiving chemotherapy.

Radiation Therapy

Radiation therapy, or radiotherapy, uses high-energy rays to damage or kill cancer cells by preventing them from growing and dividing. Similar to surgery, radiation therapy is a local treatment used to eliminate or eradicate visible tumors. Radiation therapy is not typically useful in eradicating cancer cells that have already spread to other parts of the body. Radiation therapy may be externally or internally delivered. External radiation delivers high-energy rays directly to the tumor site from a machine outside the body. Internal radiation, or brachytherapy, involves the implantation of a small amount of radioactive material in or near the cancer.  Radiation may be used to cure or control cancer, or to ease some of the symptoms caused by cancer.  Sometimes radiation is used with other types of cancer treatment, such as chemotherapy and surgery, and sometimes it is used alone.

Genetic Testing and Personalized Medicine

Personalized medicine for cancer patients represents a new approach to treatment planning in which physicians use genetic testing of the tumor to plan treatment and predict disease outcome. New genetic testing methods developed through the Human Genome Sequencing Project www.genomics.energy.gov have made it possible to look inside cancer cells at a patient’s tumor genome and see the diseased version of the patient’s normal genome. Information about the tumor can be used to identify prognostic markers (predictors of disease outcome) and therapeutic targets (features of the tumor that can be targeted by chemotherapy). This new ability to personalize treatment and predict disease outcome using tumor genome analysis represents a new era in cancer care different from the “one-size-fits-all” approach to cancer treatment that has been used in the past. This new approach is a big step forward because it has been known for a long time that even among patients with the same type of cancer, the behavior of their cancer and response to treatment, can vary widely. Through tumor genome testing, it is becoming increasingly clear that specific characteristics of cancer cells and cancer patients can have a profound impact on prognosis and treatment outcome. Although factoring these characteristics into treatment decisions sometimes makes cancer care seem more complex, it is through understanding and embracing the complexity of a tumor genome that the promise of improved outcomes becomes a reality.

What is Personalized Medicine?

Personalized medicine represents a new paradigm for medicine that is based on an understanding of the normal human genome as it was defined by the recently completed Human Genome Sequencing Project www.genomics.energy.gov . The gene-based knowledge and the biotechnology tools that were the result of this important project are becoming increasingly available to cancer patients and their physicians through clinical laboratory genetic testing of the tumor genome. Although most cancer diagnoses are initially organ-based, meaning that the patient is told that he or she has for example “breast cancer” or “prostate cancer” or leukemia, more recently it has been shown that specific characteristics of a patient’s cancer genome can have profound effects on response to treatment and prognosis.

Physicians can now incorporate knowledge about the tumor genome into a plan for the patient that is appropriate for their particular cancer. This allows physicians to be proactive and make personalized medicine-driven healthcare decisions instead of choosing treatments based on “one size fits all” conclusions drawn from large studies and clinical trials. While it is very important for physicians to practice evidence based medicine, the findings of large studies do not always apply to or benefit individual patients. However, it is only recently that laboratory methods have become clinically available to analyze the molecular profile of a patient’s cancer so that it can be used for treatment planning. For this reason, personalized medicine is a new approach to cancer care that is just beginning to be recognized by physicians and patients.

How is personalized cancer care delivered to patients?

Once a cancer diagnosis has been made, the next step is usually treatment planning. It is at this stage that a personalized analysis of the tumor genome can be made through genetic testing of the tumor. Pathologists have known for many years that tumor cells from two different patients with the same form of cancer may look virtually identical under the microscope, and yet the two patients can have very different disease outcomes. These differences in tumor behavior reflect the basic biology of the malignant genome which can be visualized by scanning the tumor genome for prognostic and predictive markers using genetic testing methods. These tests can be ordered by the patient’s oncologist or the diagnostic pathologist and ideally should be incorporated into a single patient evaluation that includes the diagnosis, identification of prognostic markers and presence of potential therapeutic targets.

What forms of cancer benefit from a personalized medicine approach?

Obtaining a complete tumor genome profile is potentially beneficial in any form of cancer. However, the tumor genome patterns of some types of cancer are better understood than others and for these types of cancer, physicians are better able to use genetic testing results to plan therapy. For example, at least four subtypes of breast cancer can be identified at the genomic level, each with a very different prognosis and response to therapy. Patients diagnosed with Luminal A breast cancer have an extremely favorable prognosis and may not need adjuvant chemotherapy. Alternatively, patients diagnosed with HER2 positive breast cancer have amplification of the HER2 gene in the tumor genome, which is an unfavorable prognostic marker which also represents a therapeutic target. Many of these patients will show a good response to a targeted therapy with the drug Herceptin.

Another examples of cancer that benefits from a personalized medicine approach is chronic lymphocytic leukemia (CLL). CLL is often treated with a “watch and wait” approach and many patients live many years with the disease before ever showing symptoms. On the other hand, some patients diagnosed with CLL develop aggressive symptomatic disease within a few months. Physicians can now use CLL tumor genome prognostic markers to distinguish indolent forms of the disease from those that will be aggressive.

References

www.PersonalizedMedicineCoalition.org

 

Genetic Testing of the Tumor Genome

Personalized cancer care begins with genetic testing of the tumor genome followed by identification of prognostic markers and therapeutic targets. Molecular testing can be performed at any time during the disease course, but is most helpful at the time of diagnosis so that information about the tumor genome can be incorporated into therapy decisions such as surgery, chemotherapy, and radiation. Prediction of disease course can often be made at the time of diagnosis and is particularly useful for forms of cancer such as chronic lymphocytic leukemia (CLL) and prostate cancer, which are often treated using a “watch and wait” approach.

What is tested by genetic methods?

In some genetic tests, tumor cells are opened to retrieve the nucleic acids DNA and RNA, while other tests examine proteins encoded by nucleic acids in blood and/or tissue. Approximately 3 billion base pairs of DNA, 30,000 genes and 500,000 proteins characterize the normal human genome. In cancer, many of these normal genome features are disrupted and reorganized by the tumor into a malignant clone (or clones) of cells which escape normal control and regulation mechanisms. This process can occur in any cell, organ, or tissue of the body, and the aggressiveness of the tumor will depend in large part on the extent that the tumor genome differs from the normal genome. In order to get a “good look” at the tumor, the pathologist will use microscopic or laboratory methods to ensure that tissue containing the tumor genome (and not normal tissue) is sent for molecular testing.

However, in some cases molecular testing of the patient’s normal genome is performed to look for information about how the patient may or may not respond to chemotherapy. This is called pharmacogenomics and examples are genetic testing of patients for mutations of genes that help determine how well patients will be able to metabolize or process medications such as CYP2D6, CYP450, TPMT, and UGT1A1. If a patient is found to have a mutation that prevents a drug from being toxic or ineffective, then a different drug can be chosen prior to starting treatment increasing the chances of treatment response and decreasing the chances of deleterious side effects.

What kinds of molecular tests are used for tumor genome testing?

Many of the methods currently used for clinical laboratory testing of tumor genomes were developed during the Human Genome Sequencing project. The method chosen for a particular case will often depend on the type of tumor and the clinical question being asked. The most commonly used techniques are listed below:

Fluorescent in situ hybridization (FISH): used to investigate whether a specific gene is lost, normal, or amplified in the tumor. Examples are amplifications of the HER2 gene in breast , ovarian and other cancers and loss of the TP53 tumor suppressor gene in CLL, multiple myeloma and other solid tumors.

Polymerase chain reaction (PCR): used to find deletions and amplifications of single genes as well as detect fusions where one gene attaches to another and forms and aberrant protein. An example is the BCR/ABL fusion gene in chronic myelogenous
leukemia (CML).

Array comparative genomic hybridization (array CGH): used to obtain genome-scale information about the tumor as well as identify gains and losses of specific genes. Examples are array CGH analysis of breast cancer for subtyping and HER2 gene status, and scanning of the CLL genome to identify prognostic markers.

References:

Utilizing the molecular gateway: the path to personalized cancer management. Clinical Chemistry 2009;55:684-697

Discussion or the applicability of microarrays: profiling of leukemias. Methods in Molecular Biology 2009;509:15-33

Genomic strategies for personalized cancer therapy. Human Molecular Genetics. 2007;16:226-232

Prognostic Markers

Prognostic markers stratify patients for risk of recurrent disease, and predictive markers are used in treatment planning for identification of therapeutic targets. There are many different types of prognostic markers including patient age, physical exam findings, and initial laboratory testing. However, prognostic markers identified within the tumor genome are becoming some of the most powerful clues that a clinician has about how a tumor will behave and what treatments may be effective. Genetic prognostic markers tell us about the tumor biology and increasingly affect the management of cancer. Many patients and their clinicians now request “prognosis and diagnosis” and expect a realistic assessment of their chances of survival and response to treatment that is based on the unique characteristics of their individual tumor.

Therapeutic Targets

A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes.

Conventional cancer treatments, such as chemotherapy and radiation therapy, cannot distinguish between cancer cells and healthy cells. Consequently, healthy cells are commonly damaged in the process of treating the cancer, which results in side effects. Chemotherapy damages rapidly dividing cells, a hallmark trait of cancer cells. In the process, healthy cells that are also rapidly dividing, such as blood cells and the cells lining the mouth and GI tract are also damaged. Radiation therapy kills some healthy cells that are in the path of the radiation or near the cancer being treated. Newer radiation therapy techniques can reduce, but not eliminate this damage. Treatment-related damage to healthy cells leads to complications of treatment, or side effects. These side effects may be severe, reducing a patient's quality of life, compromising their ability to receive their full, prescribed treatment, and sometimes, limiting their chance for an optimal outcome
from treatment.

The idea of matching a particular treatment to a particular patient is not a new one. It has long been recognized, for example, that hormonal therapy for breast cancer is most likely to be effective when the breast cancer contains receptors for estrogen and/or progesterone. Testing for these receptors is part of the standard clinical work-up of breast cancer. What is new, however, is the pace at which researchers are identifying new tumor markers, new tests, and new and more targeted drugs that individualize cancer treatment. Tests now exist that can assess the likelihood of cancer recurrence, the likelihood of response to particular drugs, and the presence of specific cancer targets that can be attacked by new anti-cancer drugs that directly target individual cancer cells.

Hormones are naturally occurring substances in the body that stimulate the growth of hormone sensitive tissues, such as the breast or prostate gland. When cancer arises in breast or prostate tissue, its growth and spread may be caused by the body’s own hormones. Therefore, drugs that block hormone production or change the way hormones work, and/or removal of organs that secrete hormones, such as the ovaries or testicles, are ways of fighting cancer. Hormone therapy, similar to chemotherapy, is a systemic treatment in that it may affect cancer cells throughout the body.

Biological Therapy

Biological therapy is referred to by many terms, including immunologic therapy, immunotherapy, or biotherapy. Biological therapy is a type of treatment that uses the body’s immune system to facilitate the killing of cancer cells. Types of biological therapy include interferon, interleukin, monoclonal antibodies, colony stimulating factors (cytokines),
and vaccines.