GPA (Graded Prognostic Assessment)

It is a prognostic index for patients with brain metastases. It was originally developed from a database of patients accrued to four Radiation Therapy Oncology Group (RTOG) protocols [1-4] for patients with brain metastases. It was validate twice by Sperduto et al. [5,6]:

GPA Criteria For Brain Metastases
Variable	0 Points	0.5 Points	1 Point
Age (years)	>60	50-59	<50
KPS	<70	70-80	90-100
No. of CNS metastases	>3	2-3	1
Extracranial metastases	Present	-	Absent

CNS = central nervous system; KPS = Karnofsky performance status.

Source: [5].

GPA Survival
GPA Score	Median OS
0-1	2.6 months
1.5-2.5	3.8 months
3.0	6.9 months
3.5-4.0	11.0 months

OS: overall survival.

Source: [7].

GPA Criteria For Brain Metastases
Variable	0 Points	0.5 Points	1 Point	2 Points	3 Points	4 Points
NSCLC/SCLC
Age	>60	50-59	<50	-	-	-
KPS	<70	70-80	90-100	-	-	-
No. of cranial metastasis	>3	2-3	1	-	-	-
Extracranial metastases	Present	-	Absent	-	-	-
Renal/Melanoma
KPS	<70	-	70-80	90-100	-	-
No. of cranial metastases	>3	-	2-3	1	-	-
Breast/GI
KPS	<70	-	70	80	90	100

CNS = central nervous system; GI = gastrointestinal; KPS = Karnofsky performance status; NSCLC = non–small-cell lung cancer; SCLC = small-cell lung cancer.
Source: [6,7].

Median OS Survival (months)
GPA Score	NSCLC	SCLC	Melanoma	Renal cell	Breast	GI
0-1	3.0	2.8	3.4	3.3	6.1	3.1
1.5-2.5	6.5	5.3	4.7	7.3	9.4	4.4
3.0	11.3	9.6	8.8	11.3	16.9	6.9
3.5-4.0	14.8	17.0	13.2	14.8	18.7	13.5
Overall	7.0	4.9	6.7	9.6	11.9	5.4

GI = gastrointestinal; NSCLC = non–small-cell lung cancer; OS: overall survival; SCLC = small-cell lung cancer.
Source: [7].

GPA is now used to stratify clinical trials [8].

Bibliographic references:

[1] Komarnicky LT, Phillips TL, Martz K, et al. A randomized phase III protocol for the evaluation of misonidazole combined with radiation in the treatment of patients with brain metastases (RTOG-7916). Int J Radiat Oncol Biol Phys. 1991 Jan;20(1):53-8. Available at: http://dx.doi.org/10.1016/0360-3016(91)90137-s.

[2] Sause WT, Scott C, Krisch R, et al. Phase I/II trial of accelerated fractionation in brain metastases RTOG 85-28. Int J Radiat Oncol Biol Phys. 1993 Jul 15;26(4):653-7. Available at: http://dx.doi.org/10.1016/0360-3016(93)90284-3.

[3] Phillips TL, Scott CB, Leibel SA, et al. Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: report of RTOG trial 89-05. Int J Radiat Oncol Biol Phys. 1995 Sep 30;33(2):339-48. Available at: http://dx.doi.org/10.1016/0360-3016(95)00168-x.

[4] Murray KJ, Scott C, Greenberg HM, et al. A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104. Int J Radiat Oncol Biol Phys. 1997 Oct 1;39(3):571-4. Available at: http://dx.doi.org/10.1016/s0360-3016(97)00341-6.

[5] Sperduto PW, Berkey B, Gaspar LE, et al. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):510-4. Available at: http://dx.doi.org/10.1016/j.ijrobp.2007.06.074.

[6] Sperduto PW, Chao ST, Sneed PK, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010 Jul 1;77(3):655-61. Available at: http://dx.doi.org/10.1016/j.ijrobp.2009.08.025.

[7] En.wikibooks.org. (2013). Radiation Oncology/Palliation/Brain Metastases/Overview - Wikibooks, open books for an open world. [online] Available at: https://en.wikibooks.org/wiki/Radiation_Oncology/Palliation/Brain_Metastases/Overview#Graded_Prognostic_Assessment_.28GPA.29 [Accessed 22 May 2016].

[8] Brainmetgpa.com. (n.d.). GPA Index. [online] Available at: http://brainmetgpa.com/ [Accessed 22 May 2016].

RANO (Response Assessment in Neuro-Oncology) criteria

They are used to assess response to first-line treatment of glioblastoma (as well as lower grade astrocytoma). They divides response into 4 types based on magnetic resonance imaging (MRI) and clinical features: 1) complete response, 2) partial response, 3) stable disease, and 4) progression.

A measurable lesions is measured as follows: either computed tomography or MRI, contrast enhancing, clearly defined margins, visible on two or more axial slices (preferably <5 mm thick with 0 mm skip), maximal diameter and second perpendicular measurement at least 10 mm in size (if slice thickness <5 mm), or 2 times slice thickness (if slice thickness >5 mm), and do not measure cystic cavity. Non-measurable lesions are generally those that do not meet the criteria above. Additionally, and worthy of specific mention, is a cystic/necrotic tumour, or one with a surgical cavity. In such cases only a solid peripheral nodular component should be measured, provided it fulfills the above "measurable" criteria. The measurements are obtained from axial post contrast T1 images. The maximal diameter is obtained, and then the second diameter is obtained at right angles to the first. The product of these measurements is then used for the purpose of comparison.

Criteria for complete response: imaging (disappearance of all enhancing disease [measurable and non-measurable], sustained for at least 4 weeks, stable or improved non enhancing fluid attenuation inversion recovery [FLAIR]/T2 lesions, and no new lesions) and clinical features (no corticosteroids [physiological replacement doses allowed], and clinically stable or improved.

Criteria for partial response: imaging (50% or more decrease of all measurable enhancing lesions, sustained for at least 4 weeks, no progression of non-measurable disease, stable or improved non enhancing FLAIR/T2 lesions, and no new lesions) and clinical features (stable or reduced corticosteroids [compared to baseline], and clinically stable or improved).

Criteria for stable disease: imaging (does not qualify for complete response, partial response or progression, and stable non-enhancing FLAIR/T2 lesions) and clinical features (stable or reduced corticosteroids [compared to baseline] and clinically stable).

Criteria for progression: imaging (25% of more increase in enhancing lesions despite stable or increasing steroid dose, increase [significant] in non-enhancing T2/FLAIR lesions, not attributable to other non-tumour causes, and any new lesions) and clinical features (clinical deterioration [not attributable to other non-tumour causes and not due to steroid decrease]).

Bibliographic reference: Luijkx, T. and Gaillard, F. (2016). RANO criteria for glioblastoma | Radiology Reference Article | Radiopaedia.org. [online] Radiopaedia.org. Available at: http://radiopaedia.org/articles/rano-criteria-for-glioblastoma [Accessed 21 May 2016].

TROG

Trans Tasman Radiation Oncology Group.

Bibliographic reference: Trog.com.au. (2013). TROG Cancer Research - Home. [online] Available at: http://www.trog.com.au/ [Accessed 21 May 2016].

Radiate

To diverge or spread from the common center. To issue and raise. It shares a common root and related meanings with other English words such as ray, radius, and radial.

Bibliographic reference: Halperin E, Wazer D, Perez C. Chapter 1 - The Discipline of Radiation Oncology. In: Halperin E, Wazer D, Perez C, Brady L, ed. Perez and Brady's - Principles and Practice of Radiation Oncology. 6th ed. Philadelphia, USA: Lippincott Williams & Wilkins, a Wolters; 2013. Box 1.2 - The Etymology of Radiate.

HiT, Health systems in Transition

The HiT profiles are country-based reports that provide a detailed description of a health system and of policy initiatives in progress or under development. They are produced by country experts in collaboration with the Observatory staff. The profiles are based on a template which, revised periodically, provides detailed guidelines and specific questions, definitions and examples needed to compile HiT. 

Bibliographic reference: Mossialos E, Allin S, Figueras J. Health Systems in Transition Template. Copenhagen, Denmark: World Health Organization & European Observatory on Health Systems and Policies; 2006 p. VII-IX. Available at: http://www.euro.who.int/__data/assets/pdf_file/0019/108820/E88699.pdf [Accessed 19 May 2016].

Gy, gray

The international unit of radiation dose: one joule per kilogram of matter.
Bibliographic reference: Fowler, J. (2006). Part I: Basic Concepts in Treatment Planning, 1. Practical Time-Dose Evaluations, or How to Stop Worrying and Learn to Love Linear Quadratics. In: S. Levitt, J. Purdy, C. Perez and S. Vijayakumar, ed., Technical Basis of Radiation Therapy, Practical Clinical Applications, 4th ed. Springer-Verlag Berlin Heidelberg, pp.3-31.

Hypofractionation

Fewer (and larger) dose/fraction than 1.8-2 Gy [1].

Bibliographic reference: [1] Fowler, J. (2006). Part I: Basic Concepts in Treatment Planning, 1. Practical Time-Dose Evaluations, or How to Stop Worrying and Learn to Love Linear Quadratics. In: S. Levitt, J. Purdy, C. Perez and S. Vijayakumar, ed., Technical Basis of Radiation Therapy, Practical Clinical Applications, 4th ed. Springer-Verlag Berlin Heidelberg, pp.3-31.

Hyperfractionation

More (and smaller) dose/fraction than 1.8-2 Gy [1]. «Fractional doses smaller than conventional, given 2 or 3 times daily to achieve an increase in the total dose given in the same overall time as conventional [2].»

Bibliographic references:

[1] Fowler, J. (2006). Part I: Basic Concepts in Treatment Planning, 1. Practical Time-Dose Evaluations, or How to Stop Worrying and Learn to Love Linear Quadratics. In: S. Levitt, J. Purdy, C. Perez and S. Vijayakumar, ed., Technical Basis of Radiation Therapy, Practical Clinical Applications, 4th ed. Springer-Verlag Berlin Heidelberg, pp.3-31.

[2] Thames HD Jr, Peters LJ, Withers HR, Fletcher GH. Accelerated fractionation vs hyperfractionation: rationales for several treatments per day. Int J Radiat Oncol Biol Phys. 1983 Feb;9(2):127-38. Available at: https://doi.org/10.1016/0360-3016(83)90089-5.

RE (relative effectiveness)

One multiplies total dose by RE to obtain BED. RE=(1+d/α/β), where d is the dose per fraction.
Bibliographic reference: Fowler, J. (2006). Part I: Basic Concepts in Treatment Planning, 1. Practical Time-Dose Evaluations, or How to Stop Worrying and Learn to Love Linear Quadratics. In: S. Levitt, J. Purdy, C. Perez and S. Vijayakumar, ed., Technical Basis of Radiation Therapy, Practical Clinical Applications, 4th ed. Springer-Verlag Berlin Heidelberg, pp.3-31.

BED (biologically effective dose)

"In fracionated radiotherapy, the total dose that would be required in very small dose fractions to produce a particular effect" [1]. It is proportional to log cell kill, and it's more conceptually useful as a measure of biological damage than a physical dose, the effects of which vary with fraction size and dose rate. Formally, it is the radiation dose equivalent to an infinite number of infinitely small fractions or a very low dose-rate. It corresponds to the intrinsic radiosensitivity (α) of the target cells when all repairable radiation damage (β) has been given time to be repaired. In linear quadratic modeling, BED=total dose x relative effectiveness (RE), where RE=(1+d/α/β), with d=dose per fraction [2]. "Otherwise known as extrapolated total dose (ETD). BED values calculated from different α/β ratios are not directly comparable. For time-dose calculations, EQD2 is preferred" [1].

Bibliographic references:

[1] Joiner, M. and van der Kogel, A. ed., (2009). Glossary of terms in radiation biology. In: Basic Clinical Radiobiology, 4th ed. London, United Kingdom: Hodder Arnold, an Hachette UK Company, p.353.

[2] Fowler, J. (2006). Part I: Basic Concepts in Treatment Planning, 1. Practical Time-Dose Evaluations, or How to Stop Worrying and Learn to Love Linear Quadratics. In: S. Levitt, J. Purdy, C. Perez and S. Vijayakumar, ed., Technical Basis of Radiation Therapy, Practical Clinical Applications, 4th ed. Springer-Verlag Berlin Heidelberg, pp.3-31.

EQD2

Biologically equivalent total dose at 2 Gy/fraction, considering certain α/β [1,2]. The total dose of a schedule using 2 Gy per fraction that gives the same log cell kill as the schedule in question [2].

Bibliographic references:
[1] Hijazi H, Chevallier D, Gal J, Chand M, Gautier M, Hannoun-Levi J. Prostate cancer boost using high-dose-rate brachytherapy: early toxicity analysis of 3 different fractionation schemes. jcb. 2013;4:203-209. doi:10.5114/jcb.2013.38657.
[2] Fowler, J. (2006). Part I: Basic Concepts in Treatment Planning, 1. Practical Time-Dose Evaluations, or How to Stop Worrying and Learn to Love Linear Quadratics. In: S. Levitt, J. Purdy, C. Perez and S. Vijayakumar, ed., Technical Basis of Radiation Therapy, Practical Clinical Applications, 4th ed. Springer-Verlag Berlin Heidelberg, pp.3-31.

α/β, alpha/beta ratio

The ratio of “intrinsic radiosensitivity” to “repair capability” of a specified tissue (in units of Gy). This ratio is large (>8 Gy) for rapidly proliferating tissues and most tumors. It is small (<6 Gy) for slowly proliferating tissues, including late normal-tissue complications. This difference is vital for the success of radiotherapy. When beta (β) is large, both mis-repair and good-repair are high. It is the mis-repair that causes the cell survival curve to bend downward [1]. It is the "dose for which the number of acutely responding cell deaths is equal to the number of late-responding cell deaths (the dose for which the linear and quadratic components of cell death are equal). (...) The α/β ratio may differ among tumor types" [2]. It is the fractionation factor [13]. For skin tumors, the α/β for 90% control rate is 13.8 Gy [3].

	List of α/β (Gy)
Heart	3 [3]
Spinal cord (radiation myelopathy)	0,87 [12], 2 [4,5]
Lung	3 [4], 4 (fibrosis), 5 (pneumonitis) [5], 2.7-4 (late reactions) [6]
Liver (fibrosis)	1 [4,5]
Kidney (nephropathy)	2 [5], 3 [4], 2-2.4 (late reactions) [6]
Parotid gland	2 [4]
Salivary glands (permantent xerostomia)	3 [5]
Lachrymal system (dry eye, ulceration)	3 [5]
Nervous system	3 [4]
Central nervous system (brain, spinal cord) (late reactions)	1.8-2.2 [6]
Eye lens (cataract)	1-2 [5]
Optic nerve (neuropathy)	2 [5]
Chiasma opticum (loss of vision)	2 [5]
Testicle	1 [4]
Testis (early reactions)	12-13 [6]
Ovary	1 [4]
Eye	1 [4]
Bone	3 [4]
Bone marrow	10 (transient hypoplasia), 5 (lethal aplasia [1 year]) [5]
Cartilage	1 [4], 6 [5]
Larynx (chronic oedema, necrosis)	2-4 [5]
Rectum (chronic inflammation, ulcer)	5 [4,5], 2.5-5 (late reactions) [6]
Urinary bladder	2 [4], 10 (acute cystitis), 5-10 (shrinkage, ulceration) [5], 3-7 (late reactions) [6]
Skin (acute erythema, dry radiodermatitis)	8.8 (erytema) (confidence interval: 6.9; 11.6) [14], 9-10 [5], 9-12 (early reactions) [6], 11,2 (desquamation) (confidence interval: 8.5; 17.6) [14], 12.3 (erytema) (confidence interval: 1.8; 22.8) [15]
Hair follicles (hair loss)	7 [5]
Mucosa (early reactions)	9-10 [6]
Oral mucosa (acute ulcerative mucositis)	10 [5]
Stomach (ulcer)	4 [5]
Small intestine (acute malabsorption)	8 [5]
Jejunum (early rections)	6-10 [6]
Small intestine (ulcer/obstruction)	4 [5]
Colon (early reactions)	9-11 [6]
Breast, adult (fibrosis/atrophy)	2-3 [5]

Human tumors	List of α/β (Gy)
Malign melanoma	0.57 [7], 1.5 [2]
Prostate adenocarcinoma	1.2 [8], 1.49 [9], 1.5-3.5 [2,10]
Bladder cancer (transitional cell carcinoma)	13 (for external beam radiotherapy [EBRT]) and 24 (for EBRT and brachytherapy) [16]
Rhabdomyosarcoma	2.8 [11]
Skin	13.8 [3]
Vocal cord	9.9 (Harrison et al., 1988, cited in [6])
Oropharynx	13-19 (Rezvani et al., 1993, cited in [6])
Larynx	25-35 (Maciejewski et al., 1988, cited in [6]), 50-infinity (Chappell et al., 1995, and Roberts et al., 1998, cited in [6])

Bibliographic references:
[1] Fowler, J. (2006). Part I: Basic Concepts in Treatment Planning, 1. Practical Time-Dose Evaluations, or How to Stop Worrying and Learn to Love Linear Quadratics. In: S. Levitt, J. Purdy, C. Perez and S. Vijayakumar, ed., Technical Basis of Radiation Therapy, Practical Clinical Applications, 4th ed. Springer-Verlag Berlin Heidelberg, pp.3-31.
[2] Beyzadeoglu, M., Ozyigit, G. and Ebnuli, C. ed., (2010). 2.6.2. Linear-Quadratic Model (LQ Model). In: Basic Radiation Oncology, 1st ed. Berlin: Springer Berlin Heidelberg, p.104.
[3] Maia MAC, Oliveira SC. Radioterapia nos tumores de pele. In: Âmbito Editores Ltda, 3.ª ed. Manual de condutas diagnósticas e terapêuticas em oncologia [Portuguese]. São Paulo, Brazil: Kowalski LP, Guimarães GC, Salvajoli JV, Feher O, Antoneli CBG (eds.); 2006; 327-330.
[4] Sfjro.fr. (2010). eLQ - Radiation Therapy Equivalent Dose Calculator. [online] Available at: http://www.sfjro.fr/ilq/en/biblio.html [Accessed 25 Jul. 2016].
[5] Dörr, W. (2009). 13 - Pathogenesis of normal-tissue side-effects. In: M. Joiner and A. van der Kogel, ed., Basic Clinical Radiobiology, 4th ed. London, United Kingdom: Hodder Arnold, an Hachette UK Company, pp.179-181.
[6] Fowler JF. The radiobiology of prostate cancer including new aspects of fractionated radiotherapy. Acta Oncol. 2005;44(3):265-76. Available at: http://dx.doi.org/10.1080/02841860410002824.
[7] Bentzen SM, Overgaard J, Thames HD, Overgaard M, Vejby Hansen P, von der Maase H, et al. Clinical radiobiology of malignant melanoma. Radiother Oncol. 1989 Nov;16(3):168-82. Available at: http://dx.doi.org/10.1016/0167-8140(89)90017-0.
[8] Brenner DJ, Martinez AA, Edmundson GK, Mitchell C, Thames HD, Armour EP. Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio) comparable to late-responding normal tissue. Int J Radiat Oncol Biol Phys. 2002 Jan 1;52(1):6-13. Available at: http://dx.doi.org/10.1016/s0360-3016(01)02664-5.
[9] Fowler JF. Biological factors influencing optimum fractionation in radiation therapy. Acta Oncol. 2001;40(6):712-7. Available at: http://dx.doi.org/10.1080/02841860152619124.
[10] Brenner DJ, Hall EJ. Fractionation and protraction for radiotherapy of prostate carcinoma. Int J Radiat Oncol Biol Phys. 1999 Mar 15;43(5):1095-101. Available at: http://dx.doi.org/10.1016/S0360-3016(98)00438-6.
[11] Timmerman RD, Mendonca M. In regard to Donaldson et al: results from the IRS-IV randomized trial of hyperfractionated radiotherapy in children with rhabdomyosarcoma-a report from the IRSG. IJROBP 2001;51:718-728. Int J Radiat Oncol Biol Phys. 2002 Dec 1;54(5):1579-80; author reply 1580. Available at: http://dx.doi.org/10.1016/S0360-3016(02)03015-8.
[12] Schultheiss TE. The radiation dose-response of the human spinal cord. Int J Radiat Oncol Biol Phys. 2008 Aug 1;71(5):1455-9. Available at: http://dx.doi.org/10.1016/j.ijrobp.2007.11.075.
[13] Dale RG, Hendry JH, Jones B, et al. Practical methods for compensating for missed treatment days in radiotherapy, with particular reference to head and neck schedules. Clin Oncol (R Coll Radiol). 2002 Oct;14(5):382-93. Available at: http://dx.doi.org/10.1053/clon.2002.0111.
[14] Turesson I, Thames HD. Repair capacity and kinetics of human skin during fractionated radiotherapy: erytema, dequamation, and telangiectasia after 3 and 5 year's follow-up. Radiother Oncol. 1989 Jun;15(2):169-88. Available at: https://doi.org/10.1016/0167-8140(89)90131-x.
[15] Bentzen SM, Christensen JJ, Overgaard J, Overgaard M. Some methodological problems in estimating radiobiological parameters from clinical data. Alpha/beta ratios and electron RBE for cutaneous reactions in patients treated with postmastectomy radiotherapy. Acta Oncol. 1988;27(2):105-16. Available at: https://doi.org/10.1016/0167-8140(89)90131-x.
[16] Pos FJ, Hart G, Schneider C, Sminia P. Radical radiotherapy for invasive bladder cancer: What dose and fractionation schedule to choose? Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1168-73. Available at: https://doi.org/10.1016/j.ijrobp.2005.09.023.