Principles of Radiotherapy in Hematological Diseases

Overview

Radiotherapy is used in hematological diseases for three separate purposes, each requiring entirely different approaches. Curative and consolidative use is added to chemotherapy, especially in Hodgkin lymphoma and some early-stage lymphomas.

The most notable development in this field is the trend toward reducing the irradiated area and dose; the reason is not questioning the efficacy but that with increased long-term survival, late effects have become the main concern. Hodgkin lymphoma is the best example of this change: as the disease became largely treatable, secondary breast cancer, cardiovascular disease, and hypothyroidism emerged decades later in young survivors.

As a result, approaches have shifted from extensive field irradiation to involved-field and involved-node approaches, doses have been reduced, and in some patients, radiotherapy has been completely avoided with response-adapted strategies. Palliative use provides rapid relief in bone pain, bleeding, mass pressure, and organ obstruction; usually short-term and low-dose regimens are used, which is important in terms of quality of life as it reduces the time the patient spends in the hospital.

Emergency use is vital in two scenarios: in malignant spinal cord compression, functional recovery strongly depends on the condition before starting treatment, and recovery is limited after the ability to walk is lost; in superior vena cava syndrome, although the picture looks dramatic, most cases do not threaten life within hours, and tissue diagnosis should be primarily attempted. This last point is linked to the most critical safety warning of this protocol: since lymphoid tissues are extraordinarily sensitive both to radiation and corticosteroids, treatment given before diagnosis can make tissue diagnosis impossible and the patient's lymphoma subtype may never be learned.

Finally, the irradiated area and dose should be recorded in the treatment summary because long-term effect monitoring entirely depends on this information.

Key considerations

• Back pain with neurological findings: malignant spinal cord compression, vertebral fracture, epidural abscess, disc disease, and leptomeningeal involvement should be differentiated (relevant protocols).
• Superior vena cava syndrome: lymphoma, lung cancer, thymoma, catheter-related thrombosis, and fibrosing mediastinitis should be considered; the sequence of diagnosis and treatment is important (relevant protocol).
• Anterior mediastinal mass: lymphoma, thymoma, germ cell tumor, and thyroid-derived masses should be differentiated; the risk of anesthesia with sedation should be assessed (relevant protocol).
• New mass in the irradiated area: secondary solid tumor, recurrence, radiation changes, and infection should be differentiated.
• Shortness of breath after radiotherapy: lung fibrosis, radiation pneumonitis, cardiac effects, anemia, and infection should be assessed (relevant protocols).
• Fatigue after radiotherapy: hypothyroidism, anemia, cardiac dysfunction, depression, and deconditioning should be differentiated (relevant protocols).
• Bone pain: bone lesion, pathological fracture, avascular necrosis, osteoporotic fracture, and infection should be considered (relevant protocols).

Why it matters

At the core of this protocol are two principles: preserving the diagnosis before starting treatment and establishing proper follow-up after treatment. Both are related not to radiotherapy itself but to the decisions surrounding it, and precisely for this reason, they directly concern hematology practice.

Preserving the tissue diagnosis targets the most common and most permanent errors in the emergency presentations of hematologic malignancies. The sensitivity of lymphoid cells to radiation and corticosteroids is an advantage in treatment; however, the same sensitivity turns into a trap at the diagnostic stage.

Administering a few doses of steroids with good intentions to a patient presenting with shortness of breath or signs of compression can shrink the mass, making the subsequent biopsy nondiagnostic. The loss here is irreversible: the patient's lymphoma subtype can never be determined, while the subtype dictates the treatment regimen, duration, and prognosis.

The result is a treatment process that can last for years based on assumptions. Therefore, even in cases that appear "urgent," a diagnostic pathway should first be sought; nowadays, this is often possible quickly with minimally invasive methods.

There are indeed situations that cannot tolerate waiting, and treatment should not be delayed in those cases, but this decision must be made with clear communication among teams. The change in the role of radiotherapy in hematology is an instructive example of how success can create new problems.

When Hodgkin lymphoma became highly treatable, attention shifted from controlling the disease to the subsequent decades of patients who survived treatment. These patients were mostly young; therefore, secondary cancers in irradiated areas, heart disease, and endocrine disorders over time became the main issue.

The conclusion drawn from this was not to abandon radiotherapy but to use it more judiciously: volumes were reduced, doses lowered, and it was shown that radiotherapy could be avoided in patients responding well at interim evaluation. This is a good example of how the assumption "every effective treatment should be applied to every patient" has been questioned; the decision is now made considering the patient's age and remaining years.

The predictability of late effects according to the area makes follow-up manageable, and this is the most practical aspect of the protocol. Initiating early breast cancer screening in a woman who has received chest irradiation, monitoring thyroid function in a patient who has received neck irradiation, discussing fertility preservation before pelvic irradiation; all of these are simple steps and all depend on knowing the irradiated area.

Therefore, record-keeping is the most tedious but most defining recommendation of this protocol: when the field, dose, and date are not written in the treatment summary, the physician seeing the patient years later cannot know which screening is necessary, and follow-up becomes arbitrary. Finally, the warning not to confuse the irradiation of blood products with therapeutic radiotherapy targets a risk arising from similarity in terminology.

They serve entirely different purposes, and skipping this step in a patient requiring irradiated products almost always leads to a complication that can be fatal.

Critical complications

• Early side effects: mucositis, dermatitis, nausea, fatigue, and organ-specific acute effects according to the irradiated area (relevant protocols).
• Radiation pneumonitis and long-term pulmonary fibrosis are seen in irradiations that involve the lung.
• Cardiac late effects: valvular disease, constrictive pericarditis, and early coronary artery disease (onco-cardiology protocol).
• Secondary solid tumors can appear in the irradiated area decades later; early breast cancer in women who received chest irradiation is the best-known example.
• Hypothyroidism and other endocrine disorders are seen in neck and cranial irradiations.
• Gonadal damage and infertility may be irreversible in pelvic irradiation (late effects protocol).
• Neurocognitive effects and pituitary dysfunction are especially seen in children after cranial irradiation.
• Loss of tissue diagnosis due to treatment given before diagnosis permanently disrupts treatment choice and prognostic assessment.

Special considerations

• Children and young adults: the group with the highest risk of late effects; there is a clear tendency to avoid radiotherapy or minimize the field, and lifelong follow-up is necessary (relevant protocol).
• Women receiving irradiation to the chest region: early breast cancer screening should be planned and started at a much earlier age than the general population.
• Patients of reproductive age: fertility preservation should be discussed before pelvic irradiation; the opportunity window is limited to before treatment (relevant protocol).
• Patients with heart or lung disease: the risk increases for irradiations involving these organs, and monitoring should be intensified.
• Transplant patients: late effects should also be considered in regimens that include total body irradiation (relevant protocols).
• Patients receiving palliative care: short schedules should be preferred, and transport difficulties and life expectancy should be included in the decision (relevant protocol).
• Patients who have previously received radiation to the same area: the decision for re-irradiation is limited due to dose constraints and requires evaluation by radiation oncology.
• Patients with connective tissue disease: in some cases, radiation toxicity may increase, and the decision should be individualized.

Follow-up plan

Follow-up in patients receiving radiotherapy is considered in two periods. In the early period, acute side effects are monitored: depending on the irradiated area, mucositis, dermatitis, nausea, and fatigue are evaluated; in patients whose lungs are included in the field, cough and shortness of breath should be assessed for radiation pneumonitis.

Supportive care needs should be met, and symptoms should be adequately controlled. Long-term follow-up is the main emphasis of this protocol and begins when treatment is completed.

The first condition of follow-up is recording the irradiated area, dose, and date in the treatment summary and providing this summary to the patient in writing; without this information, which late effects to screen for cannot be determined. Patients should be informed of the importance of keeping this document and showing it to every doctor they visit.

Follow-up should be planned according to the irradiated area. In women who received radiation to the chest area, early breast cancer screening should be started and continued at intervals according to institutional protocol; in the same patients, cardiac monitoring and assessment of respiratory functions should be planned.

In patients who received radiation to the neck area, thyroid functions should be regularly checked, and examination for thyroid nodules should be performed. Gonadal function and reproductive health should be evaluated in patients who have received pelvic irradiation.

In patients who have received cranial irradiation, pituitary functions and neurocognitive status should be monitored. In all patients, irradiated areas should be examined for secondary solid tumors, and age-appropriate national screening programs should be fully implemented.

Sun protection should be recommended for irradiated skin areas, and examination for skin cancer should be conducted. Strict control of cardiovascular risk factors is especially important in patients whose heart is in the radiation field because tissue that is already compromised is less tolerant to additional stress.

Growth, development, and endocrine functions should be monitored in patients who received radiotherapy in childhood, and the transition to adult follow-up should be done in a planned manner. Patients should be clearly informed in writing about which symptoms require medical attention; emphasis should be placed on new masses or skin lesions in the irradiated area, shortness of breath, decreased exercise capacity, and increased fatigue.