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Principles of radiotherapy


Key points

  • The clinical application of radiation oncology balances the dual goals of improved tumor control with reduced treatment-related morbidity.

  • Over time, technological and biological advances have offered many opportunities to further reduce normal tissue complications and improve tumor control with radiotherapy.

  • More recent and emerging technologies promise further improvements in the therapeutic ratio.

  • Rational application and critical appraisal of these new technologies will remain essential responsibilities for the field of radiation oncology.

Introduction

The discipline of radiation oncology involves the therapeutic application of ionizing radiation in the management of benign and malignant diseases. In fact, x-rays were used to treat a patient with ulcerated breast cancer less than 2 months after their discovery in November 1895. Therapeutic radiology, like its diagnostic counterpart, has undergone considerable evolution since then. Still, the practice of radiation oncology has at its core several fundamental concepts that have guided, and will continue to guide, management decisions.

Tumors and their neighboring organs will remain in proximity to one another. These tumors and their normal tissue counterparts will have varying responsiveness to ionizing radiation. Therefore, an ideal radiation treatment will balance optimal tumor control with acceptable acute side effects and late toxicities. Over time, new technological or biological advances will promise improved differentiation of these two populations, with better clinical outcomes. Some of these advances will actually work, shifting paradigms and reinforcing the ongoing need for rigorous testing before widespread adoption and changes to accepted standards of care.

With each new patient encounter, the radiation oncologist considers these concepts and determines the most appropriate treatment approach. A simplified algorithm is shown in Figure 4-1 , showing the general thought processes and decision points involved. The global decisions regarding treatment and goals of therapy are usually reached within a multidisciplinary context with other medical providers and informed consent of the patients and their support networks. Once the decision has been made to incorporate radiation therapy into the treatment plan, the more specific questions regarding timing, dose, treatment volume, and technology are considered. The solid and dashed arrows between the various boxes represent the interrelated nature of these questions and how they may each in turn influence the decision-making process.

Figure 4-1, Treatment algorithm. This simplified algorithm shows the general questions when encountering a patient under consideration for radiation therapy. The questions are interrelated, as shown by the dashed arrows to the right. Technological advances can often redefine what is possible when it comes to treatment delivery. This, in turn, reemphasizes the importance of clinical investigations to demonstrate the safety and superiority of these new techniques.

This chapter will briefly describe these concepts, along with specific clinical examples with various malignancies to illustrate the interplay between the decision points. We will focus on the therapeutic ratio, selection and definition of radiation target volumes, side effects and toxicity considerations, dose fractionation, and the impact of technological advances on these topics.

Therapeutic ratio

The overriding goal in patient care is to optimize treatment efficacy while minimizing toxicity. This concept is represented by the therapeutic ratio ( Figure 4-2 ). Depending on the tumor type and the surrounding normal tissues, a given amount of radiation dose will yield an expected range of both tumor control probability (TCP) and normal tissue complication probability (NTCP). The vertical white lines illustrate how an increase in dose (dashed line to solid line) leads to both higher tumor control and normal tissue complications. An example would be the dose escalation experience in prostate cancer. Multiple randomized trials have shown an improvement in prostate-specific antigen disease-free survival with higher doses of radiation at the cost of increased rectal and urinary complications.

Figure 4-2, Therapeutic ratio. The blue solid curve represents tumor control probability (TCP), whereas the red solid curve shows normal tissue complication probability (NTCP). As radiation dose increases (dashed vertical line to solid vertical line), both tumor control and toxicity are likely to increase. The final dose chosen strikes the optimal balance between the two outcomes. Various strategies can be employed to separate the two curves. Factors that sensitize tumors to radiation may shift the TCP curve to the left (dashed blue curve), whereas agents that protect normal tissues may mitigate treatment-related toxicity, shifting the NTCP curve to the right (dashed red curve).

Ideally, the two curves can be further separated, with the same radiation dose providing extremely high TCP and low NTCP. Strategies that preferentially radiosensitize tumor cells and shift the curve left (dashed blue curve) may allow for improved TCP with the same physical dose. Alternatively, techniques that preferentially protect normal tissues (dashed red curve) may reduce treatment morbidity without compromising efficacy.

In clinical practice, agents that sensitize tumors often affect normal tissues as well, leading to improved outcomes at the cost of increased toxicity. Examples of this include the use of concurrent chemotherapy with radiation compared to radiation alone in the management of lung, head and neck, cervical, esophageal, and gastrointestinal cancers. At the same time, radioprotection agents have had less clinical impact than expected. For example, the compound amifostine is U.S. Food and Drug Administration (FDA)-approved for mitigation of xerostomia in head and neck cancer patients treated with radiation alone. In practice, very few centers now utilize this agent because of its cumbersome administration, its own toxicity profile, the superiority demonstrated of concurrent chemoradiation in head and neck cancer, and the subsequent development of new radiation technologies that better spare the parotid glands.

One example where technological advances may have improved the therapeutic ratio is the use of four-dimensional computed tomography simulation (4DCT) and intensity-modulated radiotherapy (IMRT) planning in locally advanced lung cancers. Simulation with 4DCT allows for capture of respiratory motion to avoid missing the tumor, whereas IMRT planning has the capacity to deliver more conformal dose distributions with reduction in high-dose normal tissue irradiation. In a retrospective series, the use of 4DCT/IMRT compared with conventional computed tomography (CT) and planning resulted in improvements in overall survival with decreased rates of radiation-induced pneumonitis.

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