Journal of Medical Physics
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Year
: 2016  |  Volume : 41  |  Issue : 1  |  Page : 73--76

”Observations in medical physics” - Excerpts from oration of Prof. I J Das on Ramaiah Naidu Memorial Oration Award* 2015


 

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. ”Observations in medical physics” - Excerpts from oration of Prof. I J Das on Ramaiah Naidu Memorial Oration Award* 2015.J Med Phys 2016;41:73-76


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. ”Observations in medical physics” - Excerpts from oration of Prof. I J Das on Ramaiah Naidu Memorial Oration Award* 2015. J Med Phys [serial online] 2016 [cited 2019 Jul 15 ];41:73-76
Available from: http://www.jmp.org.in/text.asp?2016/41/1/73/177289


Full Text



 Observations and Curiosity



In a night, have you gazed at the sky over your head? Tiny specks of white dots known as stars fill the sky. Have you thought of what they are, how far they are, and how many of them are there? Looking at a clean beach washed with the ocean breeze, have you thought of counting the sand particles? How can we count? How many are on the earth? As far as you can see, water in the ocean; do you know how much water is there? How it was created? Can we count the water molecules? Rising on the horizon, giant mountains with snow-clad tops; do you have a curiosity about the amount of snow, height of the mountain, and number of snowflakes?

You must have walked in garden and fields during many seasons. Did you notice large and small flowers on the ground as well as on the tree tops? Have you noticed the color, shade, texture, uniqueness and brilliance, and fragrance of these flowers? Did you notice that they all come from nearly the same type of plants, shrubs, and trees but have remarkable differences? Why?

As scientists, we have developed and constantly refined methods to understand the mystery of nature with curiosity and a quest for “why?” To be a scientist, one must have a passion for observations, develop questions based on curiosity, and then try to provide a possible answer to observation. Nobel prize is the ultimate award in sciences that is given based on observations and its solutions in each discipline of science.[1]

 Time Past



Earth is nearly 4.5 billion years old, and the existence of civilized form of human probably began around 4000 years before Christ (BC). We have evolved from elements created from big-bang to chemical compounds to molecules making single cell living entity to complex systems with highly developed brain of humankind. We have evolved to think and have consensus for observations. Circular stones that had been washed and shaped by wind and rain gave curiosity to early human in developing the biggest discovery ever known, as “wheel.” How was it invented? Maybe simply watching circular stones role over with force of wind! No one knows, but it is thought that wheel was developed by early human around 3800 BC. This lead to evolution of carts for transport, gears for industry and wheels for modern industries, cars, trains, and planes.

Curiosity and observations also gave birth to religion, for example, Buddha and Christ observed human sufferings and gave their thoughts that became the respective religious texts. In the late 1800s, scientists started solving puzzles of nature by simply observing the trend, behavior, and mechanism, thus explosion of scientific discovery took place. One could say that birth of large-scale science and technology took place near 1850 and exploded which has given us every branch of science with specialization and provided every aspect of comfort and improvement in our lives including health. A pictorial view of this growth is shown in [Figure 1] along with the picture of Roentgen, Becquerel, Marie Curie, and Pierre Curie.{Figure 1}

Soon after Roentgen discovered X-rays in 1895[2] and Becquerel discovered radioactivity in 1896, followed by discovery of radium by Marie Curie and Pierre Curie in 1898, a new field of science was introduced, now known as Radiological Science. These discoveries were immediately put into patient care soon after they were discovered. Transition from simple gas-filled tube to Coolidge tube was product of observation. From kilovoltage to megavoltage, from Co-60 to linear accelerators, computed tomography (CT) scanners, magnetic resonance imaging (MRI), single photon emission computed tomography, and positron emission tomography are all remarkable devices that were invented with observation, desire to improve, and provided a step to next set of discoveries. Research in atomic and radiological physics made contributions in every aspect of science as documented by International Atomic Energy Agency.[3] Medical physics is a branch of radiological science that has evolved from a very simple to advanced technological level with high degree of complexity. The branch has further matured into four arms: radiology, radiation oncology, nuclear medicine, and health physics with super specialization to a level that most universities provide separate degrees in these fields. I will mainly concentrate now on radiation oncology, my main area of expertise. Review of 100 years of historical achievement on radiation oncology can be found in European Society for Therapeutic Radiology and Oncology book.[4] From 1995, many advances such as three-dimensional conformal therapy (3DCRT),[5] image guided radiotherapy, intensity modulated radiotherapy (IMRT),[6] stereotactic radiosurgery and therapy (SRS),[7],[8] stereotactic body radiotherapy (SBRT),[9] and particle beams [10] have evolved to provide patient care with hope of better outcome and survival.

[Inline:1]

 Cancer



World population is getting close to 8 billion people with nearly 14 million cancer cases per year. Among the cancer patients, 1/3 of these patients suffer from lung cancer.[11] It is expected that nearly 50 to 60% of these patients will be treated with radiation therapy, sometime during their care. Based on observation, it is noted that mortality in male and female for most killer diseases such as heart, stroke, and cancer is falling rapidly.[12] In addition, from nearly 1990, cancer mortality rate in every type of cancer in male and female is falling, indicative of significant gain from a combined treatment approach with radiation.[11] Unfortunately, these observations may be true only in advanced countries like the USA whereas the scenario may be different in the Indian subcontinent and the African continent which remain neglected for cancer care mainly due to large investment needed in treatment facilities. The resource allocation and disproportionate usage between USA and India are 4.5 fold.[13] India needs significant resources to tackle cancer mortality. This certainly may provide opportunity for employment, health care development, and scientific exploration.

 Observation in Treatment and Complications



Soon after discovery of X-rays, its use in cancer treatment started in major hospitals. In 1903, London Hospital in England started treating patients for breast and cervix. When these patients were followed, it was noted that they have significant skin erythema with severe desquamation and necrosis. Complications associated with kilovoltage X-rays were observed as bone fractures and radiation osteitis.[14],[15],[16],[17] These complications (desquamation, necrosis, and fracture) observed were later explained based on radiation dose to skin and bone which was not understood earlier.[18] We now know that when bone (rich in calcium, high atomic number material) is exposed with low energy beam, the photoelectric interaction gives very high dose to bone matrix and bone marrow. This is known as f factor which peaks around 2 mm Al half-value layer with the magnitude of near 4.5, suggesting that if 1 Gy radiation is given to soft tissue, bone gets 4.5 Gy. This magnitude is higher by a factor of five in bone marrow.[19],[20] This high dose/fraction explains the complications associated with early kilovoltage treatments.

 Dosimetric Accuracy



Evolution of dose (Gy) from exposure (Roentgen) took a long time. In the meantime, dosimetry had been refined, but still there were no clear guidelines as to how accurate dose should be delivered to the patients. It was not till 1987 that a clear observation between dose and outcome was noted. It was noted that a good radiation oncologist could observe difference in outcome if dose is varied +7% and −5%.[21],[22] This became seminal research work linking accuracy in dose and outcome which was soon adopted by ICRU-50[23] and recommended that the +7% and −5% dose criterion should be maintained. This was independently verified in analysis based on 8 years of follow-up in head and neck cancer patients. Using a cut-off dose and grouping patients in <56.12 Gy and >56.12 Gy, it was observed that high dose patients have 15% higher survival.[24] Evaluations based on technology also showed better survival in high energy beams compared to Co-60 beam in gynecological cancer possibly due to better depth dose.[25] Hanks et al.[26] using patterns of care data analysis showed that locoregional failures dropped significantly (>8%) in prostate, cervix, and Hodgkin disease when high energy beams were used compared to Co-60 beam.[27]

Dosimetry has been evolving from assuming patient body as water to actual elemental composition of the human body based on CT data that related electron density to radiation dose.[28] Such processes have led us to use inhomogeneity corrections that have shown a significant correlation in the outcome. Accurate dosimetry is needed; hence, model-based algorithms involving total energy released in media, dose kernel based on Monte Carlo derived pencil beam, superposition, and convolution, leading to collapsed cone algorithms have been evolved.[29],[30],[31],[32] When comparing treatment plans based on various models, large dosimetric variation is observed, indicating superiority of some algorithms.[33],[34] Similar analysis for small field treatment used in SBRT and SRS noted that pencil beam algorithm is not suitable for low-density materials like lung.[35],[36]

 Observations in Clinical Trails



Clinical trials are conducted to answer specific questions that have been observed. It is supposed to provide uniform and unbiased patient outcome data. Unfortunately, quality control in dose and related radiation outcomes are less perfect. Moore et al.[37] showed that treatment planning in radiation therapy oncology group (RTOG) clinical trials have been suboptimal. When a secondary analysis based on preplanning was performed, significant sparing of normal tissues (bladder and rectum) was achieved in the simplest and most standard IMRT in prostate cancer. Ohri et al.[38] showed that clinical protocol violation in radiotherapy has poor outcome, based on meta-analysis of cooperative clinical trials. It was shown that ≥5% dose and ≤5 mm margin delivers nearly 10% overdoses to organs at risk (OAR).

 Observations in Modern Radiation Treatment



IMRT has now become the standard of care within just 15 years of its innovation. Even though IMRT provides superior dosimetry and sparing OAR, it has larger variation in dose reflected by multi-institutional dosimetry.[39] Even with such variability, clinical outcomes have been shown as superior in IMRT. For example, in oraopharyngeal cancer comparing 3DCRT to IMRT over a minimum of 5 years of follow-up, a net gain in the outcome (15%) was achieved in IMRT arm.[40] In mediastinal lymphoma, IMRT with chemotherapy showed significant improvement in the outcome in either consolidated or salvage IMRT.[41] As mentioned earlier, lung cancer is the most common cancer in every country with usually bleaker outcome around 30% at 3 years. However, when IMRT and 3DCRT are compared, a net gain of 12% is found in IMRT-treated patients.[42] In women, breast cancer is the most common disease with good cure rate but higher complication rate associated with radiation treatment. The complication rate increases with radiation dose mainly for cardiac toxicity.[43] To reduce toxicity in breast treatment, IMRT has been used. There are several studies indicating superior outcome with IMRT compared to 3DCRT.[44],[45] In prostate cancer, dose escalation is possible with IMRT where higher dose is directly related to better outcome.[46] All these findings come with clinical observation with meticulous data collection.

 Summary



Keen observation with curiosity always leads to a new finding. It is my conviction that younger physicists should keep their eyes open and have curiosity to observe. It is often important to find a mentor, collaborator, or friend who can give critical points in the right direction. Always be critical to the observation that may lead to significant improvement. These require hard work.

(Indra J. Das, Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, Phone: 317-944-1303, Fax: 317-944-2486, E-mail: idas@iupui.edu) thanked AMPI for providing an opportunity to speak and conferring Dr. Ramaiah Naidu Oration Award-2015 on him. He also expressed gratitude to many mentors, e.g. Dr. U Madhvanath, Prof. Herb Attix, and Dr. Faiz Khan. Finally, shared the success with his wife Sununta and children Avanindra and Anita for their understanding and full support during his career.)

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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