Radiation therapy may be an integral part of the treatment of gastric cancer. However, since gastric cancer is not exclusively treated with radiation therapy, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving medical oncologists, radiation oncologists, surgeons, medical gastroenterologists, and nutritionists.
The objective of radiation therapy to the stomach is to kill cancer cells that could otherwise persist and cause the cancer to relapse. Radiation therapy uses high energy x-rays to kill cancer cells that remain in or near the stomach and surrounding lymph nodes. Radiation therapy is usually delivered to the stomach and surrounding lymph nodes from a machine outside the body, called a linear accelerator.
Radiation therapy alone is not usually recommended for primary treatment of gastric cancer because radiation administered in combination with chemotherapy appears superior when compared to treatment with radiation alone. Radiation therapy, however, is utilized as palliative therapy for patients who have inoperable gastric cancer or for patients who cannot undergo surgery or chemotherapy. Radiation therapy can also be utilized to treat patients who have a recurrence after surgery. However, in this situation patients typically also receive simultaneous chemotherapy and radiation therapy.
It is important to understand that some patients with gastric cancer already have small amounts of cancer that have spread into the lymph nodes and cannot be detected with any of the currently available tests. Undetectable areas of cancer are referred to as micrometastases. It is the presence of micrometastases that causes cancer recurrence following treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve a patient’s duration of survival and potential for a cure. The delivery of cancer treatment following local treatment with surgery is referred to as adjuvant therapy and may include chemotherapy, radiation therapy and/or biologic therapy.
Several clinical trials have suggested that chemotherapy administered after surgery may prevent some cancer recurrences; however results from other clinical trials have not shown this effect. In order to determine the effectiveness of chemotherapy after surgery in preventing recurrences, doctors in Canada analyzed results from 13 major clinical trials that compared adjuvant chemotherapy treatment to no additional treatment following surgery for gastric cancer. They found a modest benefit for patients treated with adjuvant chemotherapy. The results indicated that 65% of patients treated with surgery alone experienced a recurrence and died, compared to approximately 61% of patients receiving adjuvant chemotherapy. The greatest benefit appeared to be in patients treated with more modern chemotherapy drugs. Over the past few years, several new chemotherapy drugs have been developed that appear to have more anti-cancer activity and are being evaluated in clinical trials.
Results from a large multi-institutional clinical study also indicate that adjuvant therapy significantly improves survival for patients with gastric cancer and should become the standard of care for this disease. The trial involved over 500 patients with gastric cancer who received surgery alone or surgery plus a combination of chemotherapy and radiation. All patients in the study underwent surgery to remove their cancer and had no evidence of cancer remaining following the surgical procedure. Half of the patients then received adjuvant combination chemotherapy consisting of 5-FU and leucovorin plus radiation. Three years following therapy, 50% of patients treated with surgery followed by adjuvant chemotherapy and radiation survived, compared with only 41% of patients treated with surgery alone. Three years following treatment, 48% of patients treated with adjuvant therapy survived without a cancer recurrence, compared to only 31% treated with surgery alone. The average duration of survival following surgery was 27 months, compared with 36 months for patients receiving surgery and adjuvant therapy.
Another clinical trial evaluated adjuvant chemotherapy without radiation in gastric cancer patients. All patients in this trial had cancer that had spread to nearby lymph nodes and were eligible for curative surgery. Half of the patients received combination chemotherapy consisting of epidoxorubicin, leucovorin and 5-fluorouracil for 7 months following surgery while the other half of patients received no adjuvant therapy (control group). Five years following therapy, 30% of the patients receiving adjuvant chemotherapy were still alive, compared with only 13% from the control group. The average survival time following treatment was 31 months for patients receiving adjuvant chemotherapy and only 18 months for the control group.
Results from both of these clinical trials are consistent with previous studies indicating that adjuvant therapy improves outcomes for patients with gastric cancer. The researchers in these studies have concluded that surgery following adjuvant therapy for stage I to IV gastric cancer reduces cancer recurrences and improves overall survival compared with surgery alone. Adjuvant therapy is considered the standard treatment for patients with gastric cancer for whom all detectable cancer can first be removed by surgery.
The role of radiation therapy is limited in patients with unresectable or stage IV metastatic cancer. The primary treatment remains combination chemotherapy. Radiation therapy alone, however, can be used to decrease the symptoms from gastric cancer in patients with more advanced disease who are medically unable to receive surgery or chemotherapy or for patients who have a recurrence after surgery. However, patients with recurrent cancer usually receive combination chemotherapy.
Modern radiation therapy for gastric cancer is delivered via machines called linear accelerators that produce high energy external radiation beams that penetrate the tissues and deliver the radiation dose deep into the areas where the cancer resides. These modern machines and other state-of-the-art techniques have enabled radiation oncologists to significantly reduce side effect, while improving the ability to deliver a curative radiation dose to cancer-containing areas and minimizing the radiation dose to normal tissue. For example, with modern radiation therapy, skin burns almost never occur, unless the skin is being deliberately targeted or because of unusual patient anatomy.
After an initial consultation with a radiation oncologist, the next session is usually a planning session, which is called a simulation. The simulation session is used to determine radiation treatment fields and most of the treatment planning. Of all the visits to the radiation oncology facility, the simulation session may actually take the most time. During simulation, the patient lies on a table somewhat similar to that used for a CT scan. The table can be raised and lowered and rotated around a central axis. The “simulator” machine is a machine whose dimensions and movements closely match that of an actual linear accelerator. Rather than delivering radiation treatment, the simulator lets the radiation oncologist and technologists see the area to be treated. The room is periodically darkened while the treatment fields are being set and temporary marks may be made on the patient’s skin with magic markers. The radiation oncologist is aided by one or more radiation technologists and often a dosimetrist, who performs calculations necessary in the treatment planning. The simulation may last anywhere from fifteen minutes to an hour or more, depending on the complexity of what is being planned.
Once the aspects of the treatment fields are satisfactorily set, x-rays representing the treatment fields are taken. In most centers, the patient is given multiple “tattoos” which mark the treatment fields and replace the marks previously made with magic markers. These tattoos are not elaborate and consist of no more than pinpricks followed by ink, appearing like a small freckle. Tattoos enable the radiation technologists to set up the treatment fields each day with precision, while allowing the patient to wash and bathe without worrying about obscuring the treatment fields. Radiation treatment is usually given in another room separate from the simulation room. The treatment plans and treatment fields resulting from the simulation session are transferred over to the treatment room, which contains a linear accelerator focused on a patient table similar to the one in the simulation room. The treatment plan is verified and treatment started only after the radiation oncologist and technologists have rechecked the treatment field and calculations, and are thoroughly satisfied with the “setup”.
The majority of patients are able to complete radiation therapy without significant difficulty. Side effects and potential complications of radiation therapy are limited to the areas that are receiving treatment with radiation. The chance of a patient experiencing side effects, however, is highly variable. A dose that causes some discomfort in one patient may cause no side effects in other patients. If side effects occur, the patient should inform the technologists and radiation oncologist because treatment is almost always available and effective.
Radiation therapy to the abdominal/pelvic area may cause diarrhea, abdominal cramping or increased frequency of bowel movements or urination. These symptoms are usually temporary and resolve once the radiation is complete. Occasionally, abdominal cramping may be accompanied by nausea.
Blood counts can be affected by radiation therapy. In particular, the white blood cell and platelet counts may be decreased. This is dependent on how much bone marrow is in the treatment field and whether the patient has previously received or is receiving chemotherapy. These changes in cell counts are usually insignificant and resolve once the radiation is completed. However, many radiation therapy institutions make it a policy to check the blood counts at least once during the radiation treatments. It is not unusual for some patients to note changes in sleep or rest patterns during the time they are receiving radiation therapy and some patients will describe a sense of tiredness and fatigue.
Late complications following radiation treatment of gastric cancer are infrequent. Potential complications do include bowel obstruction, ulcers or second cancers caused by the radiation. The probabilities of these late complications are also affected by previous extensive abdominal or pelvic surgery, radiation therapy and/or concurrent chemotherapy.
The progress that has been made in the treatment of gastric cancer has resulted from improvements in multi-modality treatment and doctor and patient participation in clinical studies. Future progress in the treatment of gastric cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of gastric cancer.
Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Supportive Care.
New Adjuvant Chemo-radiation Therapy: The administration of additional treatment after surgery for the purpose of decreasing the risk of cancer recurrence is referred to as adjuvant therapy. Clinical trials have demonstrated an improvement in survival when adjuvant therapy is used to treat all stages of gastric cancer except stage IA. Clinical trials are ongoing to determine the optimal adjuvant therapy.
Ethyol®: Over the past 50 years, many drugs, called radiation protectors, have been tested in the laboratory for prevention of radiation damage to normal cells and tissues. For such drugs to work effectively, they have to protect normal cells, but not cancer cells, from radiation damage. Ethyol® is the only drug in this category that has been approved for use in patients receiving radiation for cancers of the head and neck. It is logical to assume that Ethyol® may be effective in preventing the side effects of radiation induced by treatment of gastric cancer. Ethyol® is currently being evaluated for the prevention of radiation side effects in patients with gastric cancer.
Preoperative Radiation Therapy (Neoadjuvant Therapy): Several randomized clinical trials have assessed the value of pre-operative radiation therapy in patients with localized gastric cancer undergoing gastrectomy. In these clinical trials directly comparing pre-operative radiation therapy plus surgery to surgical treatment alone, the number of patients able to undergo complete resection of all cancer and the duration of survival has not been improved with the addition of radiation therapy. However, different doses and schedules of preoperative radiation therapy continue to be evaluated in clinical trials.