The role of external beam radiotherapy in the treatment of hepatocellular cancer.

Hepatocellular carcinoma (HCC) is increasing in incidence and mortality. Although the prognosis remains poor, long-term survival has improved from 3% in 1970 to an 18% 5-year survival rate today. This is likely because of the introduction of well tolerated, oral antiviral therapies for hepatitis C. Curative options for patients with HCC are often limited by underlying liver dysfunction/cirrhosis and medical comorbidities. Less than one-third of patients are candidates for surgery, which is the current gold standard for cure. Nonsurgical treatments include embolotherapies, percutaneous ablation, and ablative radiation. Technological advances in radiation delivery in the past several decades now allow for safe and effective ablative doses to the liver. Conformal techniques allow for both dose escalation to target volumes and normal tissue sparing. Multiple retrospective and prospective studies have demonstrated that hypofractionated image-guided radiation therapy, used as monotherapy or in combination with other liver-directed therapies, can provide excellent local control that is cost effective. Therefore, as the HCC treatment paradigm continues to evolve, ablative radiation treatment has moved from a palliative treatment to both a "bridge to transplant" and a definitive treatment.

[Technical and methodical developments of radiation oncology from a physician's point of view]. / Die technischen und methodischen Entwicklungen der Radioonkologie aus ärztlicher Sicht.

Technical and methodical developments have changed radiation oncology substantially over the last 40 years. Modern imaging methods, e.g., computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasound (US), have not only improved the detection of tumors but have also become tools for computed treatment planning. Megavoltage irradiation with accelerators using photons and electrons with large and small fields, intensity modulation (IMRT), image-guided radiotherapy (IGRT), stereotactic irradiation and radiosurgery, intraoperative radiotherapy (IORT), and modern remote controlled afterloading brachytherapy have made high precision radiotherapy increasingly possible. Hadron therapy has potential for further developments. Radiation oncology today is an interdisciplinary modality and increasingly considers interactions with new drugs and differentiated surgical methods. There is a strong need for comprehensive evaluation of the new methods and also for translational research in biology of tumors and normal tissue biology as well as in medical physics and techniques.

JCOG Radiation Therapy Study Group: history and achievements.

The Radiation Therapy Study Group (RTSG) of the Japan Clinical Oncology Group (JCOG) was established in 2003. The missions of this group are to develop new standards of care with innovative, advanced technology radiation therapy, both for single- and multi-modality cancer treatment, and to improve radiation therapy quality and outcomes of JCOG trials conducted by other organ-oriented groups. In 2004, the first RTSG trial, a Phase II study of stereotactic body radiation therapy for Stage IA non-small cell lung cancer (JCOG 0403), was initiated. Four other trials are currently open for accrual. JCOG 0702 is a Phase I study of stereotactic body radiation therapy in patients with T2N0M0 non-small cell lung cancer. JCOG 0701 is a Phase III study comparing accelerated fractionation with conventional fractionation radiation therapy for T1-2N0M0 glottic cancer. JCOG 0906 is a multicenter safety trial of hypofractionated radiation therapy after breast-conserving surgery in patients with margin-negative invasive breast cancer. JCOG 1015 is a Phase II study of intensity-modulated radiation therapy with chemotherapy for loco-regionally advanced nasopharyngeal cancer. Other RTSG activities include a medical physics working group responsible for dosimetry audits; a genetic analysis working group involved in accompanying research to analyze single-nucleotide polymorphisms to identify predictors of radiation toxicities; a working group that has developed atlases of clinical target volumes for uterine cervical cancer; and participation in the Harmonisation Group to promote global harmonization of radiotherapy and radiotherapy quality assurance among trial groups. Further efforts to improve radiation therapy quality and outcomes of cancer treatment are necessary.

Combatting cancer in the third millennium--the contribution of medical physics.

In this invited opening Plenary Lecture at the 1st European Conference on Medical Physics, I indicated some of the roles of medical physics, and specifically medical radiation therapy physics, in the development of improved cancer care for the third millennium. It is said that you are only asked to predict the future if you are seriously old and/or will not be around long enough to know if you were correct. Hopefully, however, I will be able to contribute to this field for many years to come and many of my suggestions will be enacted. "Crystal ball gazing" is, however, a very unscientific process. Scientists are trained to study and analyse situations, report their findings and stop at that. "Future gazing" is not predicting the short-term developments; it is about being bold, radical and stating what today is impossible or almost unthinkable. So-called "scientific prophets" can be entertaining (which I also hope I was in this lecture) but at worst look egocentric and possibly ridiculous. I seem to have survived three previous requests to make scientific predictions [Webb S. The future of photon external-beam radiotherapy: the dream and the reality. Physica Medica 2001;17(4):207-15; Webb S. Radiotherapy physics: the next ten years of technical development. Imaging and Oncology 2005;1:43-50; Webb S, Evans PM. Innovative techniques in radiation therapy editorial, overview and crystal ball gaze to the future. In: Webb S, Evans PM, editors. Innovative techniques in radiation therapy. Seminars in Radiation Oncology 2006;16(4):193-8]. I proposed that important progress usually comes from two quite distinct directions. Firstly, there is "big hit science", that is discoveries or inventions so important that the medical world changes forever because of them. These are what people remember, what reaches the media and what make some people household names. These are rare. Secondly, there is "incremental development" which is how the vast majority of scientists work. Small parts of a big problem are dissected out, solved and contribute to the progress of a bigger field. Sometimes the second way leads to the first, often unplanned to be so. To set the scene I briefly told the story of a few famous "big hit science" stories in which medical physicists have played a leading role--the invention of X-ray computed tomography (CT), the development of intensity-modulated radiation therapy (IMRT) and the invention of the emission tomography imaging modalities: single-photon emission computed tomography (SPECT) and positron emission tomography (PET). I suggested some of the areas I consider important for development. Some are fairly easy to identify and others are more speculative and unusual. I suggested that the goal of medicine and supporting science is to ensure that people live long and die quickly and I contrasted this with the past scenarios. Digressing to philosophy I suggested that there may be a difficulty in that the highly developed world works mainly to make itself even more developed and that many developed governments and aspiring medical physicists may not be as interested as they should be in assisting developing countries. There is therefore, sadly, likely to be an ongoing imbalance of resources. Scientific publishing is also at cross roads where the need to act independently, openly and with wide availability clashes somewhat with the need to generate revenue and support learned societies. Turning to detailed observations, I described how I think the following fields can be advanced: (1) improving the diagnosis of disease, (2) improving the planning of radiotherapy, (3) improving the delivery of radiation treatment and (4) improving the assessment of response to treatment. I ended on a highly philosophical note, which is somewhat critical of how much practical medical physics is currently organised in universities and hospitals and I suggested what should be the real agenda for scientific progress.

Modern radiation treatment planning and delivery--from Röntgen to real time.

The field of radiation oncology has advanced exponentially since the discovery of X-rays just over 100 years ago. With the advent of three-dimensional treatment planning, the therapeutic index was increased by dose escalation and more accurate shielding of normal tissues. Now, even greater advances are under way with IMRT, image-guided radiation therapy, delineation and control of organ motion, and real-time imaging. Similarly, the use of particle therapies such as protons has the potential to effect even more accurate dose distributions. Clinical studies investigating these modalities will likely further increase the efficacy of radiation in years to come.

Radiotherapy for soft tissue sarcoma: 50 years of change and improvement.

Radiotherapy for soft tissue sarcoma (STS) has advanced significantly over the past 50 years. This review focuses briefly on the period from 1964 to 1999 and more substantially on the changes of the past 15 years, such as IMRT and image-guided radiotherapy (IG-RT), especially when brought together (IG-IMRT) in the same planning and delivery process to treat localized STS. In particular, the introduction of IG-RT, target volume definitions for IG-RT, and review of recent clinical trials using IG-RT to treat localized STS in extremity will be reviewed. Finally, potential investigational agents combined with IG-RT to improve outcomes in patients with localized STS are discussed.

Photons or protons for non-central nervous system solid malignancies in children: a historical perspective and important highlights.

Over the years, major advances have occurred in radiotherapy techniques, delivery, and treatment planning. Although radiotherapy is an integral treatment component of pediatric solid tumors, it is associated with potential acute and long-term untoward effects and risk of secondary malignancy particularly in growing children. Two major advances in external beam radiotherapy are intensity-modulated radiotherapy (IMRT) and proton beam radiotherapy. Their use in the treatment of children with cancer has been steadily increasing. IMRT uses multiple modulated radiation fields that enhance the conformality of the dose distribution to the target volume and avoid high doses to normal tissues. However, IMRT may be associated with increased volume of normal tissue that receives low doses and potential risk of secondary malignancy. Contrary to IMRT, proton beam radiotherapy uses a few beams and a fast dose fall-off distal to the target volume. Although both modalities require substantial personnel time and effort, the very high cost and limited availability of proton radiotherapy have constrained its widespread use. It is anticipated that both modalities may markedly improve tumor control and quality of life for long-term cancer survivors. Clinical trials with long-term follow-up are needed to confirm the premise that proton beam therapy will decrease late effects and secondary malignancies without compromising local control in pediatric patients with cancer.