Gonadotropin-releasing hormone (GnRH) antagonists

 

Gonadotropin-releasing hormone (GnRH) agonists

 

Gaseous myelography or pneumomyelography

«Myelography developed as an imaging technique to assess the status of the thecal sac, spinal cord, and nerve roots in diverse pathologic conditions. Before the development of myelography, the only definitive means of evaluating these structures was laminectomy and direct inspection [1].»

«Myelographic techniques have evolved over time. The requirement for dural puncture, although invasive, offered the opportunity to acquire cerebrospinal fluid (CSF) specimens for laboratory analysis as a part of the procedure. (...). After spinal puncture, a myelographic contrast agent was slowly injected into the subarachnoid space with fluoroscopic confirmation. (...). Myelography is an invasive procedure, requiring puncture of the subarachnoid space. The spinal puncture is generally done below the L1-2 disc space level. Subarachnoid puncture also can be performed in the cervical spine at the C1-2 level via a lateral approach, or at the craniocervical junction via a posterior midline approach. (...). Although myelography has become a relatively safe test, it is invasive. MR imaging of the spine with its improved soft tissue delineation and excellent ability to depict and characterize extradural, intradural, and intramedullary lesions has led to a significant decrease in the use of myelography [1].»

«Several contrast agents have been used for myelography»: air and other gases, Thorotrast® (a suspension containing particles of the radioactive compound thorium dioxide), Lipiodol (ethiodized oil), Abrodil (sodium iodomethane sulfonate), Conray (iothalamate meglumine), Pantopaque (iophendylate), Dimer-X (methylglucamine iocarmate), metrixamide, iohexol and other nonionics [1].

«In 1919, Dr. Walter Dandy [2] suggested that the intraspinal air that was used for pneumoencephalography could be also used for the diagnosis of intraspinal pathology. A few years later, Dandy [1922, cited by 1] reported his experience with pneumomyelography in the diagnosis of spinal cord tumors. Attractive features of gas, specifically air, as a contrast medium include low cost, lack of allergic reactions, and spontaneous reabsorption. Other gases, such as oxygen, were also used for pneumomyelography because of their greater diffusibility and more prompt resorption. Gas is a negative contrast agent, and the optical contrast provided by plain radiography or tomography was poor. Although not chemically toxic, a variety of unpleasant side effects, such as headache, nausea, and transient neurologic symptoms, were common with air myelography. (...). The other disadvantage of pneumomyelography was that fluoroscopic images could not be used; rather, radiographs were obtained using overpenetrated technique. Even with the best technique, these studies were extremely challenging to perform and interpret [1].» «Advancements in contrast media development have led to significant improvement in their safety profile [1].» «The development of water-soluble contrast media allowed the use of post-myelographic computed tomography, which was a major advance [1].»

«Although myelography has largely been supplanted by MRI [magnetic resonance imaging], it will continue to be a necessary tool and is most useful in evaluation of cerebrospinal fluid leaks and in patients unable to undergo MRI [1].»

Bibliographic references:

[1] Price DB, Ortiz AO. Myelography: From Lipid-Based to Gadolinium-Based Contrast Agents. Magn Reson Imaging Clin N Am. 2017 Nov;25(4):713-724. Available at: https://doi.org/10.1016/j.mric.2017.06.005.

[2] Dandy WE. Roentgenography of the brain after the injection of air into the spinal canal. Ann Surg. 1919 Oct;70(4):397–403. Available at: https://doi.org/10.1097/00000658-191910000-00004.

Gorlin syndrome, nevoid basal cell carcinoma syndrome, or Gorlin-Goltz syndrome

It «is a condition that affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors. (...). Individuals with Gorlin syndrome typically begin to develop basal cell carcinomas during adolescence or early adulthood. (...). Some people with Gorlin syndrome never develop any basal cell carcinomas, while others may develop thousands of these cancers. (...). Most people with Gorlin syndrome also develop noncancerous (benign) tumors of the jaw, called keratocystic odontogenic tumors (...). Individuals with Gorlin syndrome have a higher risk than the general population of developing other tumors. A small proportion of affected individuals develop a brain tumor called medulloblastoma during childhood. A type of benign tumor called a fibroma can occur in the heart or in a woman's ovaries (...). Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal abnormalities involving the spine, ribs, or skull [1].» «Ectopic calcification, particularly in the falx, is present in more than 90% of affected individuals by age 20 years [2].»

Mutations in the PTCH1 (protein patched homolog 1) gene cause Gorlin syndrome [1,3]. This protein «is the receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis. This gene functions as a tumor suppressor. The PTCH1 gene product is a transmembrane protein that suppresses the release of another protein called smoothened, and when sonic hedgehog binds PTCH1, smoothened is released and signals cell proliferation [3].» «The characteristic features of Gorlin syndrome can also be associated with a chromosomal change called a 9q22.3 microdeletion, in which a small piece of chromosome 9 is deleted in each cell. This deletion includes the segment of chromosome 9 that contains the PTCH1 gene [1].

«Gorlin syndrome is inherited in an autosomal dominant pattern [1].»

«Life expectancy (...) is not significantly different from average [2].»
These patients have a relative contraindication for radiotherapy [4].

Bibliographic reference:

[1] Gorlin syndrome. Genetics Home Reference. https://ghr.nlm.nih.gov/condition/gorlin-syndrome#genes. Published 2018. Accessed July 11, 2018.

[2] Evans DG, Farndon PA. Gorlin syndrome - Conditions - GTR - NCBI. Ncbi.nlm.nih.gov. https://www.ncbi.nlm.nih.gov/gtr/conditions/C0004779/. Accessed July 11, 2018.

[3] PTCH1. En.wikipedia.org. https://en.wikipedia.org/wiki/PTCH1. Published 2017. Accessed July 11, 2018.
[4] Singer L, Yom SS. Chapter 1 - Skin Cancer. In: Hansen EK, Roach III M. Handbook Of Evidence-Based Radiation Oncology. 3rd ed. Cham, Switzerland: Springer; 2018:10. Available at: https://doi.org/10.1007/978-3-319-62642-0.

Gleason score

«The Gleason is a grade assigned to prostate cancer specimens that reflects the degree of aggressiveness based on the tumor's resemblance to normal glandular tissue. A primary (or predominant) pattern is recorded followed by a secondary or lesser pattern. The Gleason score is the sum of the primary and secondary pattern values and can be between 2 and 10» [1].

The original Gleason grading system diagram:

Source: Gordetsky J, Epstein J. Grading of prostatic adenocarcinoma: current state and prognostic implications. Diagn Pathol. 2016 Mar 9;11:25. Available at: https://doi.org/10.1186/s13000-016-0478-2. The link to the Creative Commons Attribution 4.0 International License is http://creativecommons.org/licenses/by/4.0/.

«Grade 1: small, well-formed glands, closely packed;

Grade 2: well-formed glands, but more tissue between them;

Grade 3: darker cells, some of which have left the gland and are invading the surrounding tissue;

Grade 4: few recognizable glands with many cells invading the surrounding tissue;

Grade 5: no recognizable glands; sheets of cells throughout the surrounding tissue» [1].

The current guidelines for the Gleason grading system and recent changes from the 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma include five distinct grade groups based on the modified Gleason score groups. Grade Group 1 = Gleason score ≤6, Grade Group 2 = Gleason score 3 + 4 = 7, Grade Group 3 = Gleason score 4 + 3 = 7, Grade Group 4 = Gleason score 8, Grade Group 5 = Gleason scores 9 and 10. This new ISUP grading system is simpler and more accurately reflects prostate cancer biology, and it is recommended by the World Health Organization (WHO) to be used in conjunction with Gleason grading [10].

Bibliographic references:

[1] Shah A. 53 - Low-Risk Prostate Cancer. In: Hristov B, Lin S, Christodouleas J. Radiation Oncology. 2nd ed. Philadelphia, USA: Wolters Klumer Health; 2015:364.

[2] Gordetsky J, Epstein J. Grading of prostatic adenocarcinoma: current state and prognostic implications. Diagn Pathol. 2016 Mar 9;11:25. Available at: https://doi.org/10.1186/s13000-016-0478-2. The link to the Creative Commons Attribution 4.0 International License is http://creativecommons.org/licenses/by/4.0/.

GETUG

Groupe d'Études des Tumeurs Uro-Génitales, the French Genitourinary Study Group.

GTV (gross tumor volume)

It is the volume that includes palpable, visible, or demonstrable extent of a tumor. It may consist of the primary tumor, metastatic disease, or lymphadenopathy. It usually represents the part of the malignant growth where the tumor cell density is the largest [1]. It is the best estimate of tumor volume visualized by radiological, computed tomography scan, magnetic resonance, ultrasound imaging, or positron emission tomography [2].

Bibliographic references:

[1] Fisher, B. and Daugherty, L. (2013). G. In: L. Brady and T. Yaeger, ed., Encyclopedia of Radiation Oncology, 1st ed. Springer-Verlag Berlin Heidelberg, pp.295-304.

[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.

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].

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.