The most important contribution of radiobiology to clinical radiation oncology is in the field of fractionation. Although conventional fractionation regimen is a debatable term, altered fractionation regimens (hyper fractionation, accelerated fractionation, hypo fractionation) have been employed in a number of tumor sites with success, improving local tumor control and overall survival, albeit with occasionally observed increase in acute adverse events (Steel, 2002; Halperin et al., 2004; Smith and McKenna, 2004; Price and Sikora, 2005; Hall and Giacca, 2006). Increasing the total dose with hyper fractionation, by using a higher number of smaller fraction sizes, improved survival in head and neck cancer and lung cancer, among others, whereas accelerated fractionation, aiming to overcome accelerated repopulation of tumor clonogens, did so in lung cancer. Both types of fractionation use at least partially (e.g., in concomitant boost regimen) two fractions per day. Besides altered fractionation, hypoxia was addressed adequately in a number of studies, especially in head and neck cancer and cervix cancers, thus showing that its existence adversely influences overall treatment outcome. In addition, special chemical compounds, namely radiosensitizers and radioprotectors, hold great promise to enable differential radiosensitization of tumor cells but not normal cells (sensitizers) or preferentially protecting normal tissue (protectors) while not doing so on tumor cells/tissues, respectively. More clinical research is needed to optimize these approaches, a quest frequently identified as the ‘Holy Grail’ of radiation oncology.
The impact that new technology made upon the clinical science of radiation oncology was first observed through better imaging. With the use of CT and magnetic resonance imaging (MRI) scans, it was possible to better visualize tumors and embark on more effective treatment planning. This was followed by the wider introduction of positron emission tomography (PET) technology in pretreatment diagnosis and staging of cancer, but also in evaluations of response and follow-up efforts. Finally, PET-CT is increasingly being used for treatment planning. Besides imaging, substantial improvement in computerized sciences enabled wide introduction of powerful software programs that made treatment planning system more sophisticated and faster. Radiation oncology has slowly but definitely moved from 2D to 3D and recently to 4D treatment planning, by taking into account not only volume but also temporal (movement in time) aspects of a tumor tissue in a host. These improvements enabled more conformal radiation therapy to be performed than ever before. It became possible to precisely tailor the radiation therapy dose to the tumor and its immediate vicinity in order to raise the dose to higher levels, while protecting normal tissues. A number of dose escalation studies reconfirmed an important premise of radiation therapy that increased tumor dose should lead to an improvement in local tumor control and ultimately overall survival (Halperin et al., 2004; Smith and McKenna, 2004; Price and Sikora, 2005).
Intensity-modulated radiation therapy is an especially advanced form of 3D conformal radiation therapy that incorporates sophisticated computer-controlled radiation beam delivery and computer-optimized treatment planning design. This is achieved by varying the beam intensity within each beam portal, as opposed to the uniform beam intensities used in conventional 3D conformal radiation therapy. Although there is a huge interest in this technology, clinical experience is still confined to single institutional data, and major evidence coming from big prospective, preferably randomized, studies is lacking. This technique was mostly used in cancers of the prostate and head and neck.
In addition to intensity-modulated radiation therapy, other technological advances such as tom therapy or a special device called ‘cyber knife’ are increasingly being used in the clinic. These tools hold promise for better therapeutic ratio in various tumor types, an ultimate goal of radiation therapy.
Biology and technology meet through clinical studies, which are seen as a necessary pathway toward adoption of a method or a treatment technique, largely based on existing evidence. Practicing evidence-based oncology is one of the ‘musts’ in the contemporary setting, since it represents the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence-based oncology means integrating individual clinical expertise with the best available external clinical evidence from systematic research. The major component of this exercise comes through existing meta-analyses and prospective randomized clinical trials offering strong support pro or contra one technique, method of delivery, or treatment regimen. Radiation oncologists are largely involved in the design and performance of clinical studies, although much clinical research still needs to be done to identify and address important questions in radiation oncology.
Bibliography:
- Hall EJ and Giacca AJ (2006) Radiobiology for the Radiologist, 6th edn. Philadelphia, PA: Lippincott.
- Halperin EC, Schmidt-Ullrich RK, Perez AC, and Brady LW (2004) The discipline of radiation oncology. In: Halperin EC, Schmidt-Ullrich RK, Perez AC, and Brady LW (eds.) Principles and Practice of Radiation Oncology, 4th edn., pp. 1–95. Philadelphia, PA: Lippincott.
- Price P and Sikora K (2005) Treatment of Cancer. 4th edn. London: Arnold.
- Smith RP and McKenna WG (2004) The basics of radiation oncology. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, and McKenna WG (eds.) Clinical Oncology, pp. 535–578. Philadelphia, PA: Elsevier, Churchill Livingstone
- Steel GG (2002) Basic Clinical Radiobiology. London: Arnold.