text: Template:User author

title: Template:User author


text:
User:Josen~enwikibooks

Archived pages(not all made by me)
User:Josen/Dicefree

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: User:Josen~enwikibooks


text:
How to Make a Comic

Welcome to the How to Make a Comic Wikibooks. This wikitext was written for those interested in learning more about comics, which have existed as a creative medium for hundreds of years. This wikibook aims to provide information on web comics, comic strips, comic books and graphic novels, and will include information about creating comics either as a hobby or professionally. The goal of this book is to aid those who wish to draw, write or simply learn about the process of creating one of the world's most versatile and beloved entertainment mediums: Comics. This wikitext aims to be useful as both a guide and a quick reference. If you feel something is missing please feel free to either add it in yourself or put a request on this text's discussion page.

Basic Information

 * /History of Comics/
 * /Types of Comics/
 * /Workspace/
 * /Equipment/
 * /Format/

Story

 * /Plot/
 * /Storyboarding/
 * /Script/
 * /Characterization/

Art

 * /Anatomy/
 * /Clothing/
 * /Setting/

Digitizing

 * /Scanning/
 * /Colouring/

Publishing

 * /Online Publishing/
 * /Self-Publishing/
 * /Professional Publishing/

title: How to Make a Comic


text: User:Draganta~enwikibooks

title: User:Draganta~enwikibooks


text:
Cookbook:Chicory

| Spices and herbs

Chicory is a class of greens used for their leaves and roots.

Characteristics
All chicory varieties fall into the bitter greens category, and they tend to be quite hearty compared to more delicate greens like spinach. However, there are several different varieties of chicory with different leaf shapes, colors, and levels of bitterness (see below).

Curly endive/Frisée
As the name implies, this variety of chicory has ruffled or curly leaves. In some heads, the outer leaves are dark green and more bitter while the inner portion is yellow and milder. When used raw, it adds textural intrigue.

Belgian endive/Witloof chicory
Belgian endive is very pale yellow to white in color and smooth in texture, which is a result of it being shielded from light when grown. The flesh is watery, crisp, and relatively mild compared to other chicories. The leaves can be easily separated from the core to produce individual "cups".

Escarole
Somewhere between frisée and endive in texture, escarole has loose, broad leaves that look a lot like those of lettuce. Like frisée, the paler inner leaves are milder, while the outer leaves are tougher and more bitter.

Radicchio
Radicchio tends to look like a head of red cabbage, though much more bitter and with greater white streaking on the outside. It is extremely bitter, especially when raw, and it can overpower a dish if too much is used. However, the color is great as an accent.

Seasonality
Chicories are in season during cooler weather, so they tend to be most available during late fall through to early spring.

Selection and storage
Like other greens, choose chicories that aren't blemished, bruised, wilted, or slimy. Endives should be pale and without color. Store them for up to several days in the fridge without washing them. Some of the more compact varieties will keep for weeks—you'll generally be able to tell when they've gone bad due to wilting, browning, and sliminess.

Use
The large root of the chicory plant can be roasted, ground, and used as a coffee substitute or added to coffee grounds. Although this was originally used as a cost-effective method to extend the use of the more expensive coffee, some prefer the taste. It can be purchased alone or pre-blended with ground coffee.

Leafy and mild chicories can be included in salads, where they add some bitter textural character. Endives specifically can be used in crudité arrangements, where they can be filled or dipped. In these cases, adding a sweet, sour, and/or rich component will help balance out the bitterness. Cooking is also a good option for many chicories, as it mellows out the bitterness, and the leaves are hardy enough to tolerate it. Sautéing, roasting, and grilling all work well and add complexity of flavor through browning.

title: Cookbook:Chicory


text:
User:Robth

w:User:Robth

Just here to transwiki, at least for now.

title: User:Robth


text:
Cookbook talk:Chicory

information taken from wikipedia's entry, with non-culinary information arbitrarily deleted

title: Cookbook talk:Chicory


text:
User:Bunder

Real Name : Felipe Olmos

title: User:Bunder


text:
User talk:Ankhamun/Intro to Ancient Egyptian Civilization

test


text:
Talk:False Friends of the Slavist/Map stolica

Untitled
Stolica in Slovak languege mean: faeces, chair, capital


text:
Talk:False Friends of the Slavist/Map pokoj

Untitled
Pokoj in slovak language: rest, quiet, peace


text:
Talk:False Friends of the Slavist/Map chas

Untitled
in slovak: time, weather


text:
User talk:Cpitter

Hi my name is Christof Pitter! My interest are Computer Architecture, WCET and multiprocessor SoC's.

title: User talk:Cpitter


text:
User:EvMatra

Interesting things (websites, organisations, concepts, facts, stats etc.) we've discovered and want to share:

Ed M:

 * 02/07/06: WikiBooks- Open textbooks on any subject, including How To's. Part of the non-profit Wikimedia Foundation (i.e. same as Wikipedia). Possibly a good platform for EvMatra / HumCentre to develop and 'publish' international/sustainable development related 'modules' (building on the ISF course and IDC lecture RLOs etc.)? Nb. I'm slightly wary of the 'copycat' Wikia which seems to be a For-profit company.

title: User:EvMatra


text:
User:BulletBlog

Interesting things (websites, organisations, concepts, facts, stats etc.) we've discovered and want to share:

(Click 'edit' to the right of your name- nb alphabetical order- to add your 'bullet points' to your 'mini-blog'... hence 'bullet-blog'!)

Ed M:

 * 02/07/06: WikiBooks- Open textbooks on any subject, including How To's. Part of the non-profit Wikimedia Foundation (i.e. same as Wikipedia). Possibly a good platform for EvMatra / HumCentre to develop and 'publish' international/sustainable development related 'modules' (building on the ISF course and IDC lecture RLOs etc.)? Nb. I'm slightly wary of the 'copycat' Wikia which seems to be a For-profit company.
 * 04/07/06: Cittaslow, Italian for "slow town", is an international network of towns working towards a set of goals that aim to improve quality of life, and that have passed an assessment top be admitted as a member of the network. "Cittaslow is a way of thinking. It is about caring for your town and the people who live and work in it or visit it. It is about protecting the environment, about promoting local goods and produce, and about avoiding the ‘sameness’ that afflicts too many towns in the modern world."

Priti P:
(Add names by clicking "edit this page" at the top)

title: User:BulletBlog


text:
Horticulture/Lawns

The quest for a beautiful lawn is a well-tread path, and there are a great many techniques and tricks that can be used to make it easier.

 * What is a lawn?
 * Lawn Types
 * Lawn plants
 * Basic Lawn Care
 * Installation
 * Seed
 * Sod
 * Mowing
 * Fertility
 * Basic Weed and Pest Control
 * ../Edging/
 * Lawn Weeds
 * Lawn Pests
 * Lawn Diseases
 * Lawn Chemicals
 * Organic lawn care
 * Creating a woodland lawn

/Lawns

title: Horticulture/Lawns


text:
Horticulture/What Is a Lawn?

The definition of a lawn is often in the eye of the beholder. The most common definition is an area of mowed grasses, though lawns often contain broadleaf plants as well either as weeds or as desirable components. The common element is that lawns are maintained by regular mowing, as opposed to meadows or fields which are mown less frequently.

/Lawns

title: Horticulture/What Is a Lawn?


text:
Horticulture/Lawn Plants

Grasses

 * Bluegrasses
 * Ryes
 * Fescues

Broadleafs

 * Clovers
 * Chamomile
 * Mazus

Bulbs

 * Grape Hyacinth
 * Scilla
 * Crocus
 * Colchicum

Other Plants (sometimes encouraged)

 * Daisy (Leucanthemum vulgare)
 * Dandelion (Taraxacum)
 * Pennywort (Hydrocotyle sibthorpioides)
 * Mock Strawberry (Duchesnea indica)

/Lawns

title: Horticulture/Lawn Plants


text:
Talk:Fortran/Fortran structure and style

Moving
To comply with the standard wikibook naming policy, I will be moving this page to a section in the Fortran wikibook, if there are no objections. -Arthurv


text:
Template:Technique

Effect

 * This template changes name of the tab the article is under to "Cooking technique"
 * Unless the parameter noincludecat is specified, the article is added to Category:Cooking techniques
 * For example,  will not add the article to any categories
 * This template takes an optional sort key for the category:

title: Template:Technique


text:
Hokkien/Lesson 1

It is appropriate to start off the introduction to Min Nan with the common greeting: Lí hó. Below is a dialogue between two people meeting each other for the first time.

The Han characters provided below are for reference and are consistent with the Taiwanese Minnan Recommended Hanzi Usage (台灣閩南語推薦用字) which has been promoted by the government of Taiwan. Individual usage may vary from speaker to speaker based on preference.

Vocabulary
Note: Visit this lesson's Stroke Order subpage to see images and animations detailing how to write the following characters. Audio files of the words are linked from the POJ when available. Problems listening? See media help.

Basic Sentences
1. 我叫Amy.
 * Góa kiò Àiměi.
 * I'm called Amy.

Sentences using sī [是]
1.
 * Góa sī Tiong-kok-lâng.
 * I am a Chinese person.

2. 伊是Jenny.
 * I sī Jenny.
 * She is Jenny.

3.
 * In sī Eng-kok-lâng.
 * They are English.

1. 伊毋是Tony.
 * I m̄-sī Tony.
 * He is not Tony.

2.
 * Góa m̄-sī Bí-kok-lâng.
 * I am not American.

The question particle sī-bò· [是無]
The declarative example sentence in #1 is transformed into an interrogative in #2.

1. 伊是Jenny.
 * I sī Jenny.
 * She is Jenny.

2. 伊是Jenny是無？
 * I sī Jenny sī-bò·?
 * She is Jenny, isn't she?

The question particle ne [呢]
1. 我叫Tony, 你呢？
 * Góa kiò Tony, lí neh?
 * I'm called Tony. How about you?

2.
 * Amy sī Tiong-kok-lâng, i neh?
 * Amy is Chinese. How about him?

Question words
1. 怹是佗位的人？
 * In sī tó-ūi ê lâng?
 * Where are they from?

2.
 * siáⁿ-lâng sī Bí-kok-lâng?
 * Who is American?

3. 伊是啥人？
 * I sī siáⁿ-lâng?
 * Who is she?

title: Hokkien/Lesson 1


text:
Category:Pawpaw recipes

Recipes involving pawpaw.

title: Category:Pawpaw recipes


text:
User:Pikminkid

I dont usually look at the chat thing :)

title: User:Pikminkid


text:
Category:Pecan recipes

Recipes involving pecans.

title: Category:Pecan recipes


text:
OpenOffice.org/Math

= Adding a Formula = Math is used to insert a formula into a document. Open a new text document in OpenOffice. Then move the cursor to the point in the document where you want to insert your formula. Next select "Insert" "Object" and "Formula" from the tab, drop-down, and pop-out menus, respectively.

This will cause a new pane to appear below your text page and change the symbols at the top of the page. The formula elements are added in the lower pane while the formula itself will appear in the top pane.

When you first start Math, you should see two panes, one showing the text you have entered to get the formula (bottom pane), and one showing the rendered mathematical formula (top pane). There should also be a window open with some symbol buttons which can be used to enter code into the text window.

Example Formulas
$$a^2 + b^2 = c^2$$

a^2 + b^2 = c^2

$$\int_{-\infty }^{\infty } \frac{1}{ 1+ x^2} \, dx = \pi $$

int_{-infinity}^{infinity} {1 over {1 + x^2} } dx = %pi

$$\sum_{n = 1}^{\infty} \frac{1}{n!} = \frac{\pi^2 }{6} $$

sum from {n = 1} to {infinity} {1 over fact{n}} = {%pi^2 over 6}

$$\mathbf{F}_e = \frac{ q_1 q_2 }{4 \pi \epsilon_0 r^3 } \mathbf{\hat{r}} $$

{nitalic bold F}_e = {{ q_1 q_2 } over { 4 %pi %varepsilon_0 r^3 }} {nitalic bold hat r}

= Symbols = To quickly access a list a of non-math-specific non-standard symbols, click Catalog (the "Σ" button).

= View - Selection =

sum from{i,j} ln((P(d_{ab}^{ij}) mline C) over (P(d_{ab}^{ij})))

= Relations and Equalities =

= Set Operations =

= Common Functions =

= Operators =

= Vectors and Dots =

= Fonts, Colors and Size =

= Other =

= Enclosures - Braces, Brackets and Parentheses =

Use the curvey brackets to group formula elements. For example, if you want to divide something by n - 1, your Math formula would include "over {n -1}"

= Sub, Super =

To get a subscript, include the following in your formula "{ X sub i}"

To get a superscript, include "{X ^ Y}"

= Spaces, Returns and Alignment =

= Saving = The file with the math formulas is a text file, so just use the normal "save" or "save as" under the FILE tab.

= Printing =

OpenOffice.org/Math

title: OpenOffice.org/Math


text:
User:Edudobay

My name is Eduardo Sangiorgio Dobay, and I live and was born in São Paulo, Brazil.

My main interests are: music, (human) languages, computer programming, Mathematics, Physics.

Interwiki

 * Wikipedia
 * Portuguese Wikibooks
 * Wiktionary

title: User:Edudobay


text:
Electrodynamics/Electric Charge

Electric Force
Subatomic particles, such as the electron and the proton, exist that display an ability to affect each other without physical interaction. As an example of the type of interaction we are talking here, consider the pull of gravity between the sun and the earth: the sun and the earth are not touching each other, but they still have a relationship because of the force of gravity. Similar to gravity, the electric force is able to affect objects at a distance.

Some objects are affected by an electric force, and some objects are not. Inside the atom, to continue our example, there are three types of particles: electrons, protons, and neutrons. Of these three, the neutron is not charged and has no electric force. Protons and electrons affect each other in a complicated way, as demonstrated by this table:

Two charges will exert an electric force on each other. This force can either repel (in the case of like-signs) or can attract (in the case of opposite signs). The strength of the force depends on how far away the two charges are: if they are close the force will be strong, if they are far, the force will be weak. We will see the exact relationship that governs this force in the next chapter on Coulomb's Law.

Charge Conventions
As a matter of mathematical interest, it helps to quantify the different charges in some way. We could, in a naive way, say that an electron has a charge value of 1, and a proton has a charge value of 2. However this system would be of very limited usefulness, and it would actually take more work for us to write equations that used this system. Modern science has settled on the convention of assigning a +1 charge to a proton, and a −1 charge to an electron. The system could easily have been reversed and many of our equations would still hold true (or would need a simple sign change). However, as a matter of convention we say that electrons are negatively charged, and protons are positively charged, and that neutrons are neutrally charged (with a charge of 0).

Point Charges
When dealing with small electric charges mathematically, it is the most easy for us to consider a point charge. Point charges have mass and charge but no volume and are infinitely small. Of the fundamental particles the electron is perhaps the closest approximation to a point charge as all experimental evidence is consistent with it being a point charge. Protons etc. are believed to be composed of quarks and thus have a finite volume but in most cases can be considered as point charges.

Charge Density
We can define a function ρ(x, y, z) to be the charge density. The charge density is a measurement of the average amount of charge per unit volume. If the charge is distributed over a fine layer on a surface, it is also useful to define a superficial or surface charge density σ(x, y, z). The surface charge density measures the amount of charge per unit area.

Units
The amount of charge transferred between two points at 1 ampere over 1 second is the amount of electric charge and its derived SI unit is called a coulomb. Its base SI units are ampere-seconds.

title: Electrodynamics/Electric Charge


text:
User talk:Pikminkid

Kirby Amazing Mirror and Pokémon:Contest Basics
The book Pokémon:Contest Basics was already deleted after a WB:VFD discussion, so unfortunately your work will not be usable here on Wikibooks. Please copy/paste any content that you would like to keep, after which I will delete the page again. I recommend you move your work to a Pokemon wiki.

Additionally, Kirby Amazing Mirror in its current form is also not acceptable for Wikibooks. All of our books must be textbooks for classes taught at accredited institutions. Do you intend to write a textbook on the textbook? Walkthroughs do not fall into that category and will have to be deleted. Fortunately, StrategyWiki will gladly accept you work, so I recommend you work on your book there. Alternatively, you can contribute to the Wikipedia article on the subject. Please tell me on this page when it is okay to delete your Pokemon page and what your plans are with the Kirby book. Thanks, hagindaz 15:58, 3 July 2006 (UTC)

 * StrategyWiki is a separate project. You can get there by clicking here. Please mark pages that are no longer needed for deletion by typing on each page. Thanks, hagindaz 22:58, 3 July 2006 (UTC)

title: User talk:Pikminkid


text:
Electrodynamics/Vector Calculus Review

This page is going to review some of the necessary background information in physics and vector calculus. In this page, we will make extensive use of an analogy between vector fields and the flow of water so that you will gain intuitive understanding of the material.

The Del Operator
The del operator, ∇ is defined as follows:

 * $$\nabla = \hat{x}\frac{\partial}{\partial x } + \hat{y}\frac{\partial }{\partial y } + \hat{z}\frac{\partial }{\partial z } $$

This operator, while confusing at first, is the method by which vectors and scalars can be differentiated.

The Gradient
When ∇ operates on a scalar field, like so:

 * $$\nabla\Phi = \hat{x}\frac{\partial\Phi}{\partial x } + \hat{y}\frac{\partial\Phi }{\partial y } + \hat{z}\frac{\partial\Phi }{\partial z } $$

it simultaneously differentiates the scalar by all 3 axes (x, y, z). The result is called the "Gradient" of the scalar. The gradient is a vector that points in the direction in which the original scalar field is changing most rapidly (has the largest derivative).

In addition, $$\nabla\Phi \cdot \hat{n}$$ gives the rate of change of $$\Phi$$ in the direction of $$\hat{n}$$. Thus, the perpendicular lines to the gradient form an equipotential surface, or a surface where $$\Phi$$ are all equal.

The Divergence
The ∇ operator can be loosely treated as a "vector" whose components are the partial differential operators. If we operate on a vector field as a "dot product", we obtain:

 * $$\nabla\cdot A = \frac{\partial A_x}{\partial x } + \frac{\partial A_y }{\partial y } + \frac{\partial A_z }{\partial z } $$

This is called the "Divergence" of the vector field. It measures how much the vector "diverges" from a single point. It measures the "sources" and "sinks" of the vector field. Imagine the velocity vector field of a pool of water. The faucets are places of high positive divergence, because it is the source of the water velocity field, and the sinks (drains) are places of high negative divergence, because this is where all the water is converging.

The Curl
If we cross ∇ onto a vector field, we obtain another important operator:

 * $$\nabla\times A = \hat{x}(\frac{\partial A_z}{\partial y}-\frac{\partial A_y}{\partial z}) +

\hat{y} (\frac{\partial A_x}{\partial z}-\frac{\partial A_z}{\partial x}) + \hat{z} (\frac{\partial A_y}{\partial x}-\frac{\partial A_x}{\partial y}) $$

The resulting vector is the "Curl" of the original vector. It measures the "curling" or the "rotation" of the vector field at a single point. Thus, going back to the pool analogy, a whirlpool would be a place with a large curl. In a steady flow, the curl is 0, since the field doesn't want to curl around that point.

The Laplacian
The gradient ∇Φ introduced above is a vector field. What happens if we take its divergence?

 * $$\nabla\cdot \nabla\Phi = \nabla^2\Phi = \frac{\partial^2 \Phi}{\partial x^2}

+ \frac{\partial^2 \Phi}{\partial y^2} + \frac{\partial^2 \Phi}{\partial z^2}$$

This important operator is known as the "Laplacian". The Laplacian is also defined for vector fields:

 * $$\nabla^2 A = \hat{x}\nabla^2 A_x + \hat{y}\nabla^2 A_y + \hat{z} \nabla^2 A_z $$

The Divergence of the Curl
One might also expect to obtain an important operator by taking the divergence of a curl:

 * $$\nabla\cdot (\nabla \times A) =

\frac{\partial}{\partial x}(\frac{\partial A_z}{\partial y}-\frac{\partial A_y}{\partial z}) + \frac{\partial}{\partial y}(\frac{\partial A_x}{\partial z}-\frac{\partial A_z}{\partial x}) + \frac{\partial}{\partial z}(\frac{\partial A_y}{\partial x}-\frac{\partial A_x}{\partial y}) = 0 $$

While zero is certainly an important concept, it does not provide us with a useful operator. This identity, however, is interesting in its own right. It turns out that every vector field that is divergence-free is the curl of another vector field.

The Curl of the Gradient
Likewise,

 * $$ \nabla \times \nabla\Phi =

\hat{x}(\frac{\partial^2 \Phi}{\partial z \partial y} - \frac{\partial^2 \Phi}{\partial y \partial z}) + \hat{y}(\frac{\partial^2 \Phi}{\partial z \partial x} - \frac{\partial^2 \Phi}{\partial x \partial z}) + \hat{z}(\frac{\partial^2 \Phi}{\partial y \partial x} - \frac{\partial^2 \Phi}{\partial x \partial y}) = 0 $$

It also turns out that every vector field that has no curl is the gradient of a scalar field.

Vector Fields
Vector fields are 3 dimensional volumes, for which every point within that volume can be assigned a vector magnitude, based on some given rule. Gravity is one example of a vector field, where every point within a gravitational field is being pulled with some force magnitude towards the center. A vector field is denoted by a 3-dimensional function, such as A(x, y, z). The value of the function for each triplet is the magnitude of the vector field at that point.

Flux
In speaking of vector fields, we will discuss the notion of flux in general, and electric flux specifically. We can define the flux of a given vector field G(x, y, z), through an infinitesimal area dA, which has a normal vector n:

 * $$\operatorname{Flux}(dA, n) = G \cdot n dA$$

Which we read as "The flux passing through dA, in the direction of n".

The concept of flux originally came from hydrodynamics. The flux passing through a small surface is the amount of liquid that flows through it. If the velocity field is big, then the flux would naturally turn out to be big. Also, if the surface is parallel to the velocity field, then the flux is 0, because no water is passing through the area. It turns out flux is a very useful concept in Electrodynamics also.

If we integrate this equation with respect to dA, we get the following:

 * $$\operatorname{Flux}(A, n) = \int_A v \cdot dA$$

We can also show (although the derivation can be long), that the flux traveling into or out of a given vector field, G, can be given by the divergance of the vector field:

 * $$\operatorname{Net Flux} = \nabla \cdot G$$

Let's say that we have an arbitrary volume, V, in a vector field, G, bounded by a surface, S, with surface-area, A. Gauss' Theorem states that the flux flowing into this volume is equal to the amount of flux flowing through the surface, S.

 * $$\int_{V} (\nabla \cdot G) dV = \int_{S, V} (v \cdot n) dA$$

This formula is intuitively true because as we seen before, the divergence of a field is how much the field spreads from that point. If we add the spreading of every point inside a volume, that should be the amount that is leaving the volume through the closed surface. The flux through any closed surface of a divergence free field is 0.

Line Integration
Suppose we have a path $$\gamma$$, composed of small length elements $$ ds$$. The line integral of a vector field A is how much the field lies along the path. Formally, it is given by:
 * $$\int_{\gamma} A \cdot ds$$

Suppose that A is a curl-free field. As seen above, this means it could be written as the gradient of a certain field. Say that $$A=\nabla \Phi$$. It turns out that the line integral of A along any path connecting two points are the same. Moreover,
 * $$\int_{\gamma} A \cdot ds =\Phi(b)-\Phi(a)$$

where a and b are the start and end points of the path. Also, the line integral along a closed loop of such a field is always 0. A curl-free field is called conservative. The reason for this terminology came from mechanics: In mechanics, if you have a force field in space that is curl-free, you can always define a potential energy function, so that the work done in moving an object from a to b is the difference in potential energy. In this case, mechanical energy is conserved.

As we will see, the electrostatic field is a conservative field, whereas the magnetic field and the general electric field are not.

In general, however, the line integral of a vector field along a closed loop is nonzero. It turns out, however, that:
 * $$ \int_{\gamma} F \cdot ds=\int_{A} (\nabla \times F) \cdot dA$$. In other words, the line integral of a vector field is equal to the flux of the curl of the field through the loop. Through which surface are we finding the flux? Any surface! Any surface enclosed by the loop will suffice.

An intuitive understanding of this theorem can come as follows: the line integral of a closed loop is like how much the field wraps around the loop. However, the curl at a point gives how much the field rotates around it. Thus, the total integral over the surface gives the total "wrapping" around the loop.

Divergence and Curl
We have shown that the divergence of an arbitrary vector A is given by:

 * $$\operatorname{Divergence}(A) = \nabla \cdot A$$

and likewise, we define an operator called Curl that acts on a vector field and is defined as such:

 * $$\operatorname{Curl}(A) = \nabla \times A$$

We will be using divergence and curl throughout the rest of the chapters on electromagnetism.

title: Electrodynamics/Vector Calculus Review


text:
Java Programming/Keywords/throw

is a keyword; it 'throws' an exception. In a throw statement, the three types of objects that can be thrown are:,  , and

Syntax: ;

For example:

title: Java Programming/Keywords/throw


text:
Java Programming/Keywords/super

is a keyword. Syntax: .([zero or more arguments]); or: ([zero or more arguments]); For example:
 * It is used inside a sub-class method definition to call a method defined in the super class. Private methods of the super-class cannot be called. Only public and protected methods can be called by the keyword.
 * It is also used by class constructors to invoke constructors of its parent class.
 * Super keyword are not used in static Method.

Running the above program:

In Java 1.5 and later, the "super" keyword is also used to specify a lower bound on a wildcard type parameter in Generics.

See also: Java/Palavra-chave/super

title: Java Programming/Keywords/super


text:
Wikibooks:Featured books

Featured books are quality books that the community believes to be the best of what Wikibooks has to offer and should inspire people to improve the quality of other books. To nominate one of our Wikibooks, visit the Nominations page. All nominations should meet the minimum criteria to be featured.

Featured books
—

— — — — — — — — — — — — — — — — C# Programming (PDF) — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — Stuttering (PDF) — — — —

— — — — — — — — — — — —

— — — — —

es:Wikilibros:Libros destacados fr:Wikilivres:Vitrine it:Wikibooks:Vetrina de:Wikibooks:Empfehlenswerte Bücher pl:Wikibooks:Polecane książki pt:Wikilivros:Melhores do Wikilivros

title: Wikibooks:Featured books


text:
Wikijunior:How Things Work/Refrigerator

Who invented it?
The refrigerator cannot be said to have been invented by any one person. Many people created different types of refrigerators between 1847 and 1910 when home refrigerators became common.

How does it get power?
The main component of a refrigerator that needs power is the compressor (see below). It is essentially a pump which is driven by a motor. The motor can either be one that is powered by electricity (as in a home refrigerator), or a motor that is present for some other reason (for example, the engine in a motor vehicle provides power for the compressor in the air-conditioning system).

The Basic Refrigeration Cycle
Shown in the figure to the right is the basic refrigeration cycle. You can see that a basic refrigeration system is comprised of four main components. All of these components work together to change the state of the refrigerant in the pipe-line. Let's talk about what these different components do.

Evaporator
This is the element which removes the heat from what you are trying to cool. In the case of an air conditioning system, this would usually be the air of a room. When the low temperature refrigerant passes through evaporator, it absorbs the heat from the room air and becomes a low pressure vapor or gas. This process brings the temperature of the room air down and the room turns cooler. This cool air is then circulated back and forth in the room using fans, thus providing comfort to the occupants.

The evaporator works in a method similar to putting a small amount of rubbing alcohol on your hand and letting it evaporate. The heat of your hand causes the liquid to turn into a gas, absorbing energy in the process and making your hand feel cooler. Air conditioners and other refrigeration equipment do the same, except on a much larger scale. Unlike rubbing alcohol on the hand, however, the refrigeration cycle will begin turning this evaporated gas back to a liquid on our next stop, the "compressor."

Compressor
A compressor is a machine that can take a substance and pressurize it by forcing it into a small space. Think of the bike pump that you may use to refill your bike wheels--it uses your muscular energy to compress air into a smaller volume. Now, if you pump the tires up for a while and place your hand near the part where the air hose connects to the cylinder, it might feel quite warm. This is the result of compressing a gas into a smaller space: heat is released.

In a compressor, a powerful motor drives a piston or a high speed fan (called an impeller) that compresses the vaporized gas to a far higher pressure. But why is it needed for air conditioning or refrigeration? After absorbing heat from room air (and thus cooling it down), the refrigerant loses its pressure in order to keep its volume. This low pressure refrigerant may cause problems in circulating in the system and also make the condenser work very inefficiently. Therefore, at this stage, the compressor increases its pressure by compressing it and thus raising its temperature even further.

How do we get rid of all this heat, then? It's not good to put it back into the room where we're trying to cool! Thus, we release this hot gas to where it belongs in our next component, called the "condenser."

Condenser
This is the stage where the hot, high pressure gas exiting the compressor flows into a series of stacked pipes called the "condenser." It's usually placed somewhere else, away from the location to be cooled (like outside). Good ventilation, either through convection, forced air (fans), or even water are thus used to keep this set of pipes cool so that we can get rid of all the heat built up so far. Essentially, the condenser's purpose is to transform the hot vaporized refrigerant back into a cooler liquid so that the refrigeration cycle can start once again.

Something you can observe similarly to a condenser is to watch how a cold metal spoon held over a boiling pot will build up small drops of water over a period of time. This is because the cooler surface of the spoon will lower the temperature of steam nearby, and cause the water molecules to come closer to each other, thus turning the steam back into liquid. Heat energy is released during this process, causing the spoon to get warm.

One last step remains before the cooling process can start over at the evaporator: the thermal expansion valve.

Thermal expansion valve
So far, the refrigerant has been a low pressure liquid, a low pressure vapor, a high pressure vapor, and finally a high pressure liquid. Now we need a way to take all that pressure that the compressor has created out of the system. This is where the expansion valve comes in. It allows the refrigerant to expand and lose its pressure which causes a drastic reduction in temperature also. Now the refrigerant is a low pressure and low temperature liquid again, ready to go back through the evaporator and cool some more air!

The thermal expansion valve is a very important step in the refrigeration process. Think of it as a sort of carefully-drilled pinhole that separates a high pressure location from a low pressure location. The (now cold) high pressure liquid, coming out of the condenser, is trying very hard to force through such a small space into the evaporator, where it can once again boil and absorb heat. However, if the hole wasn't present, and instead a normal pipe were to be placed there instead, there would be no pressure difference, and no cooling would take place! Thus, manufacturers of air conditioners, refrigerators, and other such equipment need to carefully choose the right expansion valve size so that the correct pressures are established. Too large of a difference (as in, a too-small hole), and the compressor might overheat, the evaporator could ice over, and other nasty problems might occur. Too small of a difference (a larger hole), and there wouldn't be enough cooling!

The thermal expansion valve's size dilemma could be solved in large refrigeration systems by placing a special "thermal bulb" near the part where the evaporator connects to the compressor. A long, thin tube connects the bulb to a large diaphragm mounted on the valve's body, which controls the size of the hole. The thermal bulb contains a mix of various liquids that makes it act a lot like a traditional alcohol thermometer you might have used when you get sick. Essentially, its purpose is to tell the valve when the evaporator temperature is too low (this means the hole is too small), or when the evaporator temperature is too high (the hole is now too big), and change the size of the hole so that the opposite effect will take place. Since the temperature of almost all of the pieces in the refrigeration system are always rising and falling, the thermal expansion valve's job "governs" the whole thing to cool at the right temperature--all the time.

Now you know
Now you know the basic principles behind the refrigeration cycle. These principles can be applied to virtually any refrigeration system: your parents' car, your home's and school's air conditioners, your refrigerator/freezer, and even odd items like soda and ice cream machines! Without refrigeration, we would be very uncomfortable and wouldn't be able to prevent things from getting too hot.

How dangerous is it?
Refrigerants in old refrigerators and air conditioners were bad for the environment. The most commonly used refrigerant used today is non-toxic, but because of its density it displaces oxygen and can cause you to suffocate if released in an airtight room.

What does it do?
It lowers the temperature of a space.

Size
Refrigeration systems can vary in size from the smallest "dorm fridges" meant for college and office use, to gigantic cooling towers around industrial buildings. Even then, their processes are quite similar; only the parts differ in size most of the time.

For example, small piston-based freezer compressors can be about the size of a small soccer ball in an average refrigerator, use normal 120 volt house current, and run on one motor cranking out out perhaps 1/10 of a horsepower. The largest centrifugal compressors used in cooling large buildings can be as big as a bus, run 3-phase 480 volt current, and utilize multiple motors that are over a thousand horsepower each!

Condensers are also another part that can differ vastly in size. Dorm refrigerator condensers are about 12-16" in width and height, and contain perhaps just a few feet of copper tubing. This is because the amount of heat that has to be removed from such a small space is quite minimal. On the other hand, industrial condenser systems are often many stacks of refrigerant-filled tubes encased in very large drums with lots of water (or a mix of water and a sort of antifreeze) flowing through them. This "cooling water" is pumped to a separate cooling tower outside (the largest of which may look like nuclear reactor cooling towers), where it flows through troughs while air from large fans disperse the heat into the atmosphere. The water is then recirculated via pumps back to the condensing drums.

Technology
There is another technology by which the Refrigeration (cooling) is achieved. This is called the Vapor Absorption process.

In this technology dual fluids are used as refrigerant. One of which is in gas form and another is in liquid form. The main property of the liquid that is employed is the ability of the liquid to absorb the gas.

In the room where cooling is to be done the gas (vapor) is absorbed  by the liquid there by creating a low pressure and temperature. Once the liquid is saturated with vapor, it is then transferred to the coil which is placed outside the room. Here the temperature is high and at higher temperature the liquid releases the vapor.

How has it changed the world?
Refrigerators allow us to keep food longer; how would ice creams be kept from melting in the summer if we lacked fridges? Air conditioning lets us cool down houses and buildings in the summer, reducing the chance of heat stroke.

What idea(s) and/or inventions had to be developed before it could be created?
Air conditioning systems are surprisingly easy to understand. The refrigerant cycle can be a very exciting example of how useful changing matter can be. Refrigeration allows us to live our lives more comfortably and more cost effectively. With a couple of basic concepts you can be on your way to knowing all about AC&R, air conditioning and refrigeration, in no time at all.

Heat Transfer
It is important to remember that air conditioning systems do not cool the air that passes through them, they remove the heat from it. Any time two objects are placed near each other they have a tendency to equalize their respective temperatures. The greater the difference in temperature, the faster this heat transfer occurs. Heat transfer always occurs from a hot object to a cold object. Heat transfer occurs through one of three ways: radiation, convection, and conduction.

Radiation
Radiation is when heat moves through a surface without that surface contacting the origin of the heat. For example, if there is a fire in the fireplace, the fire will radiate heat and you will be able feel it if you are nearby, even though you are not touching it. -

Convection
Convection is the natural circulation of heat. You may already know that warmer air rises and cooler air sinks. This process is known as convection. Many objects that we use every day use this principle, for example, an oven. You place your food in the middle of an oven with heating elements at the bottom. The elements heat up the air and it rises until it cools enough to begin sinking where it is heated again by the elements, thus creating a circulation of the air inside the oven.

Conduction
Conduction is probably the form of heat transfer that you are most familiar with. Conduction occurs when two materials come into contact with each other. For example, you place your hand on a hot plate. By coming into direct contact with the plate you allow the heat to be transferred to your much cooler hand.

You now know the basic principles of heat transfer, the single most important concept when learning how an air-conditioning system operates.

States of Matter
Before we continue we will review the states of matter and how they relate to each other. Matter exists in four states: solid, liquid, gas, and plasma. Matter can change states when heat transfer occurs. By heating a liquid you can cause it to become a gas. For example; water exists in three states, solid (ice), liquid, and gas (evaporated water). When you heat a block of ice it will melt and become a liquid. When you heat the liquid it turns into a vapor which can be observed as steam.

Pressure Creates Heat
When matter is compressed, its temperature increases. Conversely, when pressure is released from matter, the temperature of the matter decreases. This can be observed with an aerosol spray can. After expelling the matter from the container, which reduces the pressure of the contents of the container, the temperature of the container is decreased.

Refrigerant
Refrigerant is a colorless compound that is used in air conditioning and refrigeration systems for its unique temporal properties. The most common type used is R-134a. In the past R-12 and R-22 were common, but their use was discontinued when it was discovered that, when released into the atmosphere, they had an adverse effect on the environment. Refrigerant changes from a gas to liquid and back again many times throughout the basic refrigerant cycle. Refrigerant is naturally very cold. In fact, its boiling point is only -26.08°C, or -14.94°F! (At atmospheric pressure, commonly 101,4 kPa. )This property makes it ideal for use in refrigeration. Its ability to maintain low temperatures in a liquid state allows it to absorb a large amount of heat from the air around it. You should never handle refrigerant, it can be very dangerous if you are not trained to use it. When refrigerant comes into contact with a flame it can break down into gases that can be harmful if they are inhaled.

title: Wikijunior:How Things Work/Refrigerator


text: Category:Book:Systems Theory

title: Category:Book:Systems Theory


text:
Adventist Youth Honors Answer Book/ADRA/Refugee Resettlement

1. Be at least in the 8th grade.
If you attend school outside the North American Division or under a different structure, this is equivalent to being in the grade that most 13 year-olds are in.

2. Explain why refugees from other countries arrive in your nation. What are the causes and what governmental authorities must certify each case before the individual or family is allowed to travel?
The 1951 Refugee Convention spells out that a refugee is someone who "owing to a well-founded fear of being persecuted for reasons of race, religion, nationality, membership of a particular social group or political opinion, is outside the country of his nationality, and is unable to, or owing to such fear, is unwilling to avail himself of the protection of that country."

Refugees are different from migrants. Migrants, especially economic migrants, choose to move to other countries in search of better economic or educational opportunities for themselves or their families. Refugees flee from their home countries save their lives or preserve their freedom. They have no protection from their own country. In fact, it is often their own government that is threatening to persecute them. If other countries do not welcome them, and help them, then they may be condemning them to death - or to an intolerable life without the ability to survive and without rights. Poverty does not make a person a refugee. Persecution does.

The United Nations High Commission for Refugees (UNHCR) is the primary initial screening organization determining refugee status. Once an individual or family has passed the UNHCR screening and been verified as having refugee status, the case is open for countries that resettle refugees to consider the case and conduct an interview. Some of these countries also have alternate routes to refugee status, but the primary route is UNHCR referral.

Of the more than 14 million refugees of concern to UNHCR around the world, less than one per cent is submitted for resettlement. As of 2015, 28 countries participate in UNHCR's resettlement program. The United States is the world's top resettlement country, while Australia, Canada and the Nordic countries also resettle significant numbers of refugees annually. However, while the United States resettles a significantly higher total number of refugees than any other country, Australia and Canada resettle more refugees per capita than the United States.

Each country has its own government entity for processing refugee cases for resettlement. Here are a few: - In the United States, the U.S. Department of Homeland Security Refugee Processing Center processes refugee cases. - In Canada, The Immigration and Refugee Board (IRB) makes decisions about refugee claims. - In Australia, the Immigration Department determines which refugee cases are accepted for resettlement.

(For this honor, be able to name the government entity that processes refugee cases in your country.)

3. List the immediate needs that a refugee has when they arrive in your country. Describe the feelings that the refugee may have about a new language, culture and environment.
Needs: shelter will be the first, then water, clothing, food, and possibly medical attention.

It can be overwhelming to come to a place where language and culture vary so much from your own. During an already stressful period of having to abandon all that you know, entering a strange land may cause some individuals under such stress to need a great deal of social assistance to gain control over their emotions.

Environmental changes can be anything from a strange place to sleep to a geographically dynamic change. As above, stress can be emotionally overwhelming and those socio-cultural differences must be attended to. Among these can be the change of "home environment," having lost your home and now having to dwell in some form of shelter or housing not known to you before. Geographic changes can be a harsh physical barrier: those from areas normally wet have trouble adjusting to dry seasons. Consistently different temperatures can cause illness as well. For such matters medical professionals are needed to help gain control over physical illnesses that arise.

== 4. Find out about the organizations in your community that assist refugees and immigrants. Use the telephone or visit the office of at least one such organization and ask how they would assist if your local church were to cosponsor a newly-arrived refugee with ADRA or Adventist Community Services. ==

In the United States, you can visit the Refugee Processing Center web site to find a list of State, Federal, and volunteer organizations who assist refugees.

In New Zealand, visit the RMS Refugee Resettlement web site.

Visit Citizenship and Immigration Canada for information in Canada.

In the United Kingdom, try the Information Center about Asylum and Refugees (ICAR).

For Australia, visit The Refugee Council of Australia (RCOA).

If you know of an organization for a country not listed here, please add it. You can find them by using an Internet search engine with the terms "Refugee resettlement" and your country of interest.

== 5. Write a plan of at least 500 words describing the arrangements that your local church could make if it were the cosponsor with ADRA or Adventist Community Services for a refugee arriving in your community. == You can contact Xtreme Youth Resources International for a sample plan. We will work to having posted directly here.

== 6. Interview a person who immigrated to your country. Ask them about the contrast between the culture in your community and the community where they were raised. Ask them to describe the process they went through to become comfortable in your community. Take notes during the interview. == Note that there is no requirement for the person you interview to be a refugee. You can meet this requirement by interviewing any person who has moved to your country.

Most people are proud of their heritage, and even though an immigrant has left his or her homeland, they are likely to still be very fond of their place of birth. Because of this, it is very important that you check your attitude. Do not go in thinking that your interviewee is glad to be away from some dismal wasteland and isn't he glad to be in your obviously superior country. While he may have left a dismal situation, he will likely still long to return there - that's home to him. Be mindful of this possibility.

== 7. Give a report of at least 10 minutes duration to a Sabbath School program, Pathfinder Club, church committee, or civic club on what you have discovered in completing the requirements for this honor. Tell why the refugee situation is so important and make specific recommendations to the group of ways in which they can help meet the needs of refugees. == This report should be given before any concerned or potentially involved group you have access to. You should remember (as when giving any report) to include proper acknowledgement for those resources you gathered information from. If possible, when giving information of such education to a group, make copies of your outline and any charts, posters, or pictures you used to give as handouts to attendees.


text: Category:Book:SPARC Assembly

title: Category:Book:SPARC Assembly


text: Category:Book:MIPS Assembly

title: Category:Book:MIPS Assembly


text:
Category:Book:X86 Assembly

he:קטגוריה:אסמבלי x86 pt:Categoria:Assembly x86

title: Category:Book:X86 Assembly


text:
Radiation Oncology/Hodgkin

 * Official Guidelines
 * Staging
 * Overview
 * Adult early stage
 * Lymphocyte predominant
 * Early stage general
 * Early stage favorable
 * Adult advanced stage
 * Pediatric
 * Randomized Evidence
 * EORTC HD Trials ("H" trials)
 * German HD Trials ("HD" trials)
 * Review

title: Radiation Oncology/Hodgkin


text:
Radiation Oncology/Hodgkin/Early stage

Early Stage Hodgkin's Disease

Treatment Overview

 * Initially, high cure rate was achieved through prophylactic extended field radiation, to adjacent areas next to involved regions
 * Since staging laparotomy showed infradiaphgragmatic occult disease in ~20% patients with supradiaphragmatic disease, prophylactic radiation was extended to para-aortic fields or all lymph node areas. Spleen was either removed or irradiated
 * Local and distant relapses continued to occur despite extensive RT; combined chemotherapy (MOPP) and radiation (EFRT) was shown to result in 80-90% 5-year survival. Randomized trials showed that combined chemotherapy + EFRT and combined chemotherapy + IFRT was superior to RT alone
 * Because maximal combined treatment resulted in significant toxicity (late sepsis in splenectomy patients, second malignancies, heart and lung disease, and sterility), efforts were undertaken to reduce radiation field size after administration of chemotherapy
 * to be continued ...
 * German HD8 and EORTC H9 showed ABVD x4 cycles + IFRT 30 Gy as the superior approach for unfavorable disease over chemotherapy + EFRT
 * to be continued ...

RT alone

 * Princess Margaret Hospital; 1992 (1978-86) PMID 1555977 — "Analysis of supradiaphragmatic clinical stage I and II Hodgkin's disease treated with radiation alone." Gospodarowicz MK et al. Int J Radiat Oncol Biol Phys. 1992;22(5):859-65.
 * Retrospective. 250 patients. Stage cI-II with supradiaphragmatic disease; no adverse prognostic factors. Variety of radiation techniques (involved field, mantle, or extended field).
 * 90% cause-specific survival at 8-years with RT alone

 * Stanford
 * 1973 PMID 4126721 — "Survival and relapse rates in Hodgkin's disease: Stanford experience, 1961-71." (Kaplan HS, Natl Cancer Inst Monogr. 1973 May;36:487-96.)
 * No abstract
 * 1968 PMID 4170945 -- "Clinical evaluation and radiotherapeutic management of Hodgkin's disease and the malignant lymphomas." (Kaplan HS, N Engl J Med. 1968 Apr 18;278(16):892-9.)
 * No abstract
 * 1962 PMID 14453744 — "The radical radiotherapy of regionally localized Hodgkin's disease." (Kaplan HS, Radiology. 1962 Apr;78:553-61.)
 * No abstract

RT vs Chemo

 * NCI-Canada HD.6
 * See results below (at )

 * NCI
 * PMID 2033427, 1991 — "Radiation therapy versus combination chemotherapy in the treatment of early-stage Hodgkin's disease: seven-year results of a prospective randomized trial." Longo DL et al. J Clin Oncol. 1991 Jun;9(6): 906-17.
 * Randomized. 136 pts. Stage I,II,and IIIA1. Pts with peripheral IA treated with RT alone (n=30). The rest were randomized to RT alone vs MOPP.
 * Median f/u 7.5 yrs. For pts with peripheral IA dz treated with RT alone, all pts cured. For pts randomized to RT, 96% CR, 35% relapsed, 20% died. For MOPP, 96% CR, 13% relapsed, 7% died. 10-yr DFS 60% RT vs 86% (SS). 10-yr OS, 76% vs 92% (p=.05). MOPP superior for the following subgroups: Stage IIIA1, massive mediastinal dz, no B symptoms, ESR >20, 4 or more involved sites, age < 40.

 * Italian trial
 * PMID 1740677, 1992 (1979-82) — "Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study." Biti GP et al. J Clin Oncol. 1992 Mar;10(3): 378-82.
 * 89 pts. Stage pI-IIA. Randomized to mantle field followed by para-aortic vs MOPP x 6 cycles.

Chemo + RT

 * Stanford, 1993 (1980-88) - PMID 7683016 — "Hodgkin's disease with bulky mediastinal involvement: effective management with combined modality therapy." Behar RA et al. Int J Radiat Oncol Biol Phys. 1993 Apr 2;25(5):771-6.
 * Retrospective. 48 pts with bulky disease. Chemo followed by mantle field RT.
 * 9-yr OS 84%, FFR 88%
 * Good results for combined modality treatment.

RT vs Chemo+RT

 * EORTC H5, 1988 (1977-82)
 * See details at

 * EORTC H8-Favorable (1993-1999) -- MOPP-ABV x3 + IFRT vs STNI
 * Randomized. 542 patients, Stage I-II supradiaphragmatic HD, favorable (Prognostic score using EORTC H7 criteria 1-5). Arm 1) MOPP-ABV x3 cycles + IFRT vs. Arm 2) STNI alone
 * 2007 PMID 17989384 -- "Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease." (Ferme C, N Engl J Med. 2007 Nov 8;357(19):1916-27.). Median F/U 7.7 years
 * H8-F Outcome: 5-year EFS MOPP-ABV + IFRT 98% vs. STNI 74% (SS); 10-year OS 97% vs. 92% (SS)
 * Conclusion: For favorable disease, MOPP-ABV x3 cycles + IFRT is superior to STNI

 * German HD7 (1993-1998) -- EFRT alone vs. ABVD x2 + EFRT
 * Randomized. 650 patients, Stage IA-IIB without risk factors. Treated with 1) RT alone vs. 2) ABVD x 2 cycles + RT RT same in both arms, given as EFRT 30 Gy + IFRT 10 Gy
 * 2007 PMID 17606976 -- "Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial." (Engert A, J Clin Oncol. 2007 Aug 10;25(23):3495-502.). Median F/U 7.2 years
 * 7-year outcome: no difference in survival (92% vs. 94%, NS), but significant difference in DFS RT alone 67% vs. CRT 88% (SS). Treatment relapse more successful for RT only arm
 * Second malignancies: no difference, 0.8% per year, highest in older patients & B-symptoms
 * Conclusion: Combined modality more effective than EF-RT alone

 * SWOG S9133 (1989-2000) -- STNI vs doxorubicin/vinblastine + STNI
 * Randomized. Closed after 2nd analysis due to superior outcome of CMT arm. 348 patients with clinical Stage IA-IIA, supradiaphragmatic HD, no staging laparotomy. Arm 1) subtotal lymphoid irradiation (STNI 36/20 or 40/20) or chemo (doxorubicin/vinblastine x3 cycles) + STNI
 * 2001 PMID 11709567 — "Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease." (Press OW et al. J Clin Oncol. 2001 Nov 15;19(22):4238-44.) Median F/U 3.3 years
 * Outcome: FFS CMT 94% vs. STNI only 81% (SS); only 3 and 7 deaths in the arms
 * Toxicity: well tolerated
 * Conclusion: Good outcome possible without staging laparotomy; combined modality superior to STNI alone

 * EORTC H7-Favorable (1988-1993) -- EBVP x6 + IFRT vs STNI
 * Randomized. 333 patients with Stage I supradiaphragmatic HL, favorable (prognostic score 1-5). No staging laparotomy. Arm 1) STNI alone (36 Gy uninvoled, 40 Gy involved fields) vs. Arm 2) EBVP x6 cycles + IFRT (36-40 Gy)
 * 2006 PMID 16754934 — "Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials." (Noordijk EM, J Clin Oncol. 2006 Jul 1;24(19):3128-35.) Median F/U 8.7 years
 * Outcome: 10-yr EFS STNI 78% vs. EBVP+IF 88% (SS). OS similar at 92%.
 * Conclusion: Combined chemo + IFRT is superior STNI alone

Chemo vs Chemo+RT
Meta-analysis
 * Cologne; 2010 PMID 19951972 -- "Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review." (Herbst C, Haematologica. 2010 Mar;95(3):494-500. Epub 2009 Nov 30.)
 * Meta-analysis. 5 randomized trials of chemo alone vs chemo-RT, 1245 patients, early stage HL
 * Outcome: tumor control better with chemo-RT (HR 0.4, SS), OS better with chemo-RT (HR 0.4, SS)
 * Conclusion: Adding RT to chemotherapy improves local tumor control and overall survival

Randomized

 * EORTC H10(ONGOING) - chemotherapy alone vs chemo-RT (involved nodes - INRT) in pts with PET CR after 2 cycles of chemo
 * See details at H10

 * EORTC H9-F (1998-2004) - chemo followed by IFRT 36 Gy vs 20 Gy vs observation
 * See details at H9F

 * Italy; 2007 PMID 17786707 -- "Randomized comparison of consolidation radiation versus observation in bulky Hodgkin's lymphoma with post-chemotherapy negative positron emission tomography scans." (Picardi M, Leuk Lymphoma. 2007 Sep;48(9):1721-7.)
 * Randomized. 260 patients with bulky HL, treated with induction chemo. Then if no residual disease on PET, randomized to +/- IFRT 32 Gy. Median F/U 3.3 years
 * Outcome: Biopsy malignancy observation 14% vs. RT 4% (SS). All relapses in chemo-only group were in the bulky site/contiguous LNs
 * Conclusion: PET accuracy 86% with 14% false-negative rate; addition of RT improves EFS in PET-negative patients

 * NCI-Canada HD.6 / ECOG (1994-2002) - ABVD vs RT (or ABVD+RT)
 * 405 pts. Stage I-IIA, no bulky disease. Also excluded pts with low risk disease (single node, NS or LP histology, limited to high neck or epitrochlear). Stratified into favorable or unfavorable groups (unfavorable, any of: age >40, ESR > 50, MC or LD histology, 4 or more sites of disease). Staging eval included CT but not PET.
 * Randomized to:
 * 1) ABVD alone. All received at least 4 cycles. Restaged after cycles 2 and 4. If achieve CR after 2nd cycle, then had 4 cycles only. If not achieve early CR, then receive a total of 6 cycles.
 * 2) Radiation therapy. Favorable group received RT alone (subtotal nodal). Unfavorable group received 2 cyles ABVD then RT (subtotal nodal). Dose was 35 Gy / 20 fx (175 cGy/fx).
 * Trial closed to accrual early (goal was 450 pts) after results of EORTC trial that showed excellent results for involved field (rather than subtotal nodal) RT in combination with chemotherapy.
 * 2005 PMID 15837968 — "Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group." Meyer RM et al. J Clin Oncol. 2005 Jul 20;23(21):4634-42.
 * Median f/u 4.2 yrs. 399 pts evaluated. No difference in EFS (86 v 86%) or OS (96 vs 94%). Benefit for freedom from disease progression for RT arm (87 vs 93%, SS).  In unfavorable group, freedom from disease progression was superior in the combined modality arm, but no difference in OS.
 * Note: Compare to preliminary results from H9F (listed above)
 * 2012 (12 yrs): PMID 22149921 -- "ABVD Alone versus Radiation-Based Therapy in Limited-Stage Hodgkin's Lymphoma" (Meyer RM, N Engl J Med. 2012 Feb 2;366(5):399-408.) -- Median f/u 11.3 yr
 * 12-yr OS 94% (ABVD alone) vs 87% (STNI), SS. FFDP 87% (ABVD) vs 92% (STNI), SS. EFS 85% vs 80%, NS.
 * In favorable group, no difference in OS, FFDP, EFS at 12 years with ABVD vs STNI
 * In unfavorable group, ABVD+STNI had better 12 yr FFDP (94% vs 86%, SS) but worse 12 yr OS (81% vs 92%, SS) than ABVD alone
 * More secondary cancers (23 vs 10 pts), cardiac events (26 vs 16 pts) with STNI
 * Conclusion: ABVD alone was associated with a higher rate of overall survival owing to a lower rate of death from other causes.
 * Criticisms: Antiquated RT techniques with large field (STNI) and high dose (35 Gy) may have increased late toxicity, RT group had older patients (45% vs 36% over age 40), 5 of 24 deaths in RT arm from "other causes" including drowning/suicide/Alzheimer's vs. no such deaths in chemo alone arm, ABVD x 2c may be insufficient systemic therapy for unfavorable disease

 * Tata Memorial Hospital; India (1993-1996) -- Initial chemotherapy, PET-, then +/- RT
 * Randomized. 179 patients (251 enrolled, and 179 achieved CR). Stage I-IV (I-II in ~55%), ABVD x6. If clinical/radiographical CR, then Arm 1) EBRT vs Arm 2) observation. RT given as IFRT 84%, inverted Y 11%, mantle 4%, TNI 1%. Dose 30 Gy with 10 Gy boost to bulky disease
 * 2004 PMID 14657226 -- "Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need?" (Laskar S, J Clin Oncol. 2004 Jan 1;22(1):62-8. Epub 2003 Dec 2.) Median F/U 5.25 years
 * Outcome: 8-year EFS no RT 76% vs RT 88% (SS), 8-year OS 89% vs 100% (SS). RT improved outcomes for age <15 years, B-symptoms, advanced stage, and bulky disease
 * Conclusion: Addition of consolidation RT improves EFS/OS in patients achieving CR after ABVD

Retrospective

 * SEER (1988-2006)
 * Adult stage I-II. No chemo information available.
 * 2012 PMID 22251881 -- "Declining use of radiotherapy in stage I and II Hodgkin's disease and its effect on survival and secondary malignancies." (Koshy M, Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):619-25.) -- Median f/u 4.9 yrs
 * 12,247 pts; 51.5% received RT. Decreasing utilization of RT: 62.9% RT use 1988-91, vs 43.7% in 2004-06.
 * 5-yr OS 76% (RT) vs 87% (no RT); HR 1.72. No increase in secondary malignancies.
 * Conclusion: survival benefit associated with use of RT

Meta-analysis

 * International HD Collaborative Group; 1998 PMID 9508163 -- "Influence of more extensive radiotherapy and adjuvant chemotherapy on long-term outcome of early-stage Hodgkin's disease: a meta-analysis of 23 randomized trials involving 3,888 patients. International Hodgkin's Disease Collaborative Group." (Specht L, J Clin Oncol. 1998 Mar;16(3):830-43.)
 * Meta-analysis. 1,974 patients in 8 trials comparing more vs less extensive RT and 1,688 patients in 13 trials comparing RT + chemo vs RT alone
 * Outcome: More extensive RT reduces risk of failure (31% vs. 43%, SS), but there was no impact on 10-year OS (77% vs 77%). Addition of chemotherapy reduced risk of failure (15% vs. 33%), with no impact on 10-year OS (79% vs. 76%)
 * Conclusion: More extensive RT field or addition of chemo improve disease control, but have no effect on OS due to effective salvage. Less intensive primary treatment appears to achieve similar survival rates as more intensive treatment

Extent of radiation field (with chemotherapy)
Please see HD radiation fields for overview

STNI vs. IFRT

 * EORTC H8-U (1993-1999) -- MOPP-ABV x6 + IFRT vs MOPP-ABV x4 + IFRT vs MOPP-ABV x4 + STNI
 * Randomized, 3 arms. 996 patients, Stage I-II supradiaphragmatic HD, unfavorable (Prognostic score using EORTC H7 criteria >=9). Arm 1) MOPP-ABV x6 cycles + IFRT vs. Arm 2) MOPP-ABV x4 cycles + IFRT vs. Arm 3) MOPP-ABV x4 cycles + STNI. RT dose CR 36 Gy, PR 40 Gy
 * 2007 PMID 17989384 -- "Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease." (Ferme C, N Engl J Med. 2007 Nov 8;357(19):1916-27.). Median F/U 7.7 years
 * Outcome: 5-year EFS 84% vs. 88% vs. 87% (NS); 10-year OS 88% vs. 85% vs. 84% (NS)
 * Conclusion: Best strategy for unfavorable disease is MOPP-ABV x4 cycles + IFRT

 * Milan (Italy)(1990-96) - ABVD x 4 cycles plus subtotal nodal vs involved field RT
 * Randomized. 136 patients. Stage I (unfavorable) or IIA (favorable or unfavorable), clinical staging. ABVD x4 cycles. Arm 1) subtotal nodal irradiation vs. Arm 2) involved field RT. RT began 4 weeks after chemo and restaging. Dose for CR 36 Gy, for PR/unconfirmed CR 40 Gy. For STNI, 30.6 Gy to uninvolved mantle + para-aortic + spleen. Treated postchemotherapy volumes
 * 2004 PMID 15199092 (2004) - "ABVD plus subtotal nodal vs involved-field radiotherapy in early-stage Hodgkin's disease: long-term results." (Bonadonna G, J Clin Oncol. 2004 Jul 15;22(14):2835-41.) Median F/U 9.7 years
 * Outcome: CR STNI 100% vs. IFRT 97%. 12-year FFP 93% vs. 94% (NS); 12-year OS 96% vs. 94% (NS)
 * Conclusion: ABVD + IFRT is feasible to use involved-field instead of more extensive RT

EFRT vs. IFRT

 * German HD8 (1993-98) -- COPP/ABVD x2 cycles plus EFRT vs IFRT
 * Randomized. 1064 patients, with early stage unfavorable HD. Clinical stages I-II with 1 or more risk factors, as well as stage IIIA without risk factors. Risk factors were large mediastinal mass, extranodal, massive splenic involvement, elevated ESR, or more than 2 lymph node groups. IIB may have only elevated ESR or more than 2 lymph node groups but no other risk factors. Treated with COPP/ABVD x 2 cycles, then randomized to Arm 1) EFRT 30 Gy vs. Arm 2) IFRT 30 Gy. A 10 Gy boost to bulky disease. Supradiaphragmatic EF RT was a mantle + PA + splenic hilum / spleen. Subdiaphragmatic EF RT was an inverted Y plus mini-mantle.
 * 5-years; 2003 PMID 12913100 — "Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group." (Engert A, J Clin Oncol. 2003 Oct 1;21(19):3601-8.) Median F/U 4.5 years
 * Outcome: 5-year FFTF EFRT 86% vs. IFRT 84% (NS), 5-year OS EFRT 91% vs. 92% (NS). No difference in CR, PFS, relapse rate, death, and second neoplasm
 * Toxicity: Nause/vomiting, pharyngitis, GI toxicity, leukopenia, and thrombocytopenia worse in EFRT arms
 * Conclusion: RT volume reduction from EFRT to IFRT produces similar results and less toxicity
 * Elderly; 2007 PMID 17071932 -- "Poorer outcome of elderly patients treated with extended-field radiotherapy compared with involved-field radiotherapy after chemotherapy for Hodgkin's lymphoma: an analysis from the German Hodgkin Study Group." (Klimm B, Ann Oncol. 2007 Feb;18(2):357-63. Epub 2006 Oct 27.)
 * Subset analysis. 89 patients age >60. Poorer risk profile
 * Outcome: 5-year FFTF EFRT 58% vs. IFRT 70% (SS), OS 59% vs. 81% (SS)
 * Toxicity: Grade 3-4 EFRT 26% vs. IFRT 9%
 * Conclusion: Treatment with EFRT of elderly patients after chemo has negative impact on survival

 * GPMC (Groupe Pierre-et-Marie-Curie, France)(1976-81) -- MOPP x3 plus EFRT vs IFRT
 * Randomized. 335 patients, Stage I-IIIA. No staging laparotomy or splenectomy. MOPP x3 cycles. Then randomized to Arm 1)EFRT vs Arm 2) IFRT. Supradiaphragmatic disease = mantle + para-aortic field. Infradiaphragmatic disease = inverted Y + supraclavicular fields. Stage III = total nodal irradiation. Dose 40 Gy @ 2-2.5 Gy/fx. For unfavorable prognosis patients, additional MOPP x3 given
 * 1985 PMID 3838188 — "Extended versus involved fields irradiation combined with MOPP chemotherapy in early clinical stages of Hodgkin's disease." (Zittoun R, J Clin Oncol. 1985 Feb;3(2):207-14.) Median F/U 3.5 years
 * Outcome: 6-year DFS EFRT 90% vs. IFRT 86% (NS), OS 93% vs. 90% (NS). Relapse in nonirradiated areas EFRT 3/11 (27%) vs IFRT 12/18 (67%)
 * Conclusion: Combined chemotherapy and EFRT did not result in definite advantage and may represent overtreatment for many patients

INRT

 * British Columbia; 2008 (1989-2005) PMID 18838714 -- "Involved-nodal radiation therapy as a component of combination therapy for limited-stage Hodgkin's lymphoma: a question of field size." (Campbell BA, J Clin Oncol. 2008 Nov 10;26(32):5170-4. Epub 2008 Oct 6.)
 * Retrospective. 325 patients with limited-stage HD Stage (IA 29%, IIA 71%), treated with chemotherapy + RT. EFRT used 1989-1996 (39%), IFRT used 1996-2001 (30%), INRT used 2001-2005 (31%). INRT defined as prechemo nodal volume with margin <=5 cm. No PET. Median F/U of living patients 6.7 years
 * Outcome: Relapse rate EFRT 3% vs. IFRT 5% vs. INRT 3% (NS). No marginal recurrences after INRT. 5-year PFS 97% and OS 95%. 10-year PFS 95% and OS 90%
 * Conclusion: Reduction in field size to involved nodes + 5cm appears safe, without increased risk of recurrence

Field Guidelines

 * German GHSG; 2008 PMID 18956517 -- "Involved-node radiotherapy in early-stage Hodgkin's lymphoma. Definition and guidelines of the German Hodgkin Study Group (GHSG)." (Eich HT, Strahlenther Onkol. 2008 Aug;184(8):406-10.)
 * CTV encompasses initial location and extent of disease, taking displacement of normal tissue into account. Margin 2 cm axial and 3cm craniocaudal; can be reduced to 1-1.5 cm. Mediastinum is different
 * Conclusion: Concept of INRT has been proposed; field sizes will further decrease compared to IFRT

 * EORTC-GELA
 * 2008 PMID 18555548 -- "The conundrum of Hodgkin lymphoma nodes: to be or not to be included in the involved node radiation fields. The EORTC-GELA lymphoma group guidelines." (Girinsky T, Radiother Oncol. 2008 Aug;88(2):202-10. Epub 2008 Jun 12.)
 * Three step process in treatment position: 1) PET scan review, 2) CT scan review, 3) prechemo vs postchemo changes used as surrogate of initial involvement
 * Conclusion: Guidelines developed for cervical and axillary lymph nodes. This manuscript is considered an addendum to prior publication
 * 2006 PMID 16797755 -- "Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines." (Girinsky T, Radiother Oncol. 2006 Jun;79(3):270-7. Epub 2006 Jun 22.)
 * New concepts for RT fields in patients with early stage HD after chemotherapy
 * Conclusion: First attempt at concept of involved-node radiotherapy (INRT) guidelines
 * Comment (PMID 17125861): Implementing INRT requires using 4DCT to ensure appropriate margins for motion
 * Author response (PMID 17125861): Goal is to propose easy reasonable guidelines, emphasis on pretreatment volumes

 * Memorial Sloan-Kettering; 2002 PMID 12078908 -- "The involved field is back: issues in delineating the radiation field in Hodgkin's disease." (Yahalom J, Ann Oncol. 2002;13 Suppl 1:79-83.)
 * Design guidelines and field border recommendations

RT dose

 * Meta-analysis in 1966 (PMID 5947345) suggested a continuous reduction in recurrence rates with RT alone up to 40 Gy, after which toxicity became excessive
 * Subsequent dose-response analyses (PMID 1620882, PMID 10348284) suggested a plateau between 30 - 40 Gy for subclinical disease, but reduction in control for bulky disease below 40 Gy
 * German HD4 randomized trial showed that 30 Gy was adequate compared to 40 Gy
 * Both German HD10 and EORTC H9 suggest (reported as abstract only; 4/2010) that 20 Gy after chemo CR may be sufficient as a consolidation dose
 * Please also see the Early Stage Favorable page for more trials

 * German Hodgkin Lymphoma Study Group; 1997 (1983-93)
 * Review of pts from randomized trials HD1 and HD5. Pts were treated with COPP/ABVD followed by RT. Randomized to 20 vs 40 Gy extended field in HD1; received 30 Gy in HD5. Bulky dz always received 40 Gy.
 * No difference in freedom from failure or survival in the different dose arms, supporting that 20 Gy is acceptable for nonbulky disease. Bulky disease should receive 40 Gy.

Chemotherapy Regimens

 * HD13 (ongoing trial)
 * Randomized to 2 cycles of ABVD, ABV, AVD, or AV. All followed by 30 Gy IF-RT.

 * Italian IIL (1997-2001) -- ABVD + IFRT vs. EVE + IFRT
 * Randomized. 181 patients, age <65, with unfavorable Stage IA-IIA (bulky, subdiaphragmatic, ESR >40, Extranodal, hilar, or >3 LN areas). Arm 1) doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) + IFRT vs. Arm 2) epirubicin, vinblastine, etoposide (EVE) + IFRT. RT 36/20, postchemo volumes, to all initially involved regions
 * 5-years; 2008 PMID 18180244 -- "ABVD plus radiotherapy versus EVE plus radiotherapy in unfavorable stage IA and IIA Hodgkin's lymphoma: results from an Intergruppo Italiano Linfomi randomized study." (Pavone V, Ann Oncol. 2008 Apr;19(4):763-8. Epub 2008 Jan 6.)
 * Outcome: 5-year RFS ABVD 95% vs. EVE 78% (SS); OS 95% vs. 92% (NS)
 * Conclusion: EVE chemotherapy significantly worse than ABVD

 * EORTC H7-Unfavorable (1988-1993) -- EBVP x6 + IFRT vs MOPP/ABV + IFRT
 * Randomized. Stopped early due to worse outcome in EBVP arm. 389 patients with Stage I supradiaphragmatic HL, unfavorable (prognostic score >=9). No staging laparotomy. Arm 1) EBVP x6 + IFRT 36-40 Gy vs. Arm 2) MOPP/ABV x6 + IFRT 36-40 Gy
 * 2006 PMID 1675493 — "Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials." (Noordijk EM, J Clin Oncol. 2006 Jul 1;24(19):3128-35.) Median F/U 8.7 years
 * Outcome: 10-yr EFS EBVP 68% vs. MOPP/ABV 88% (SS). OS 79% vs 87% (SS). Low control rate in irradiated areas
 * Conclusion: EBVP is inferior to MOPP/ABV, IFRT with poor chemo not sufficient in these patients with high tumor burden

Toxicity
Gonadal function
 * EORTC/GELA, 2007 PMID 17515571 -- "Gonadal function in males after chemotherapy for early-stage Hodgkin's lymphoma treated in four subsequent trials by the European Organisation for Research and Treatment of Cancer: EORTC Lymphoma Group and the Groupe d'Etude des Lymphomes de l'Adulte." (van der Kaaij, J Clin Oncol. 2007 Jul 1;25(19):2825-32.)
 * Prospective. FSH levels measured in 4 EORTC trials (H6-H9). 355 patients with FSH >1 year for fertility; 349 patients with FSH <1 years for fertility recovery. Median F/U 2.7 years
 * Elevated FSH: RT 3% vs. non-alkylating chemo (ABVD or EBVP) 8% vs. alkylating chemo (MOPP, MOPP/ABV, BEACOPP) 60% (SS). Recovery of fertility at 19 months: non-alkylating 82% vs. alkylating 52% (SS). Dose-dependent.
 * Conclusion: Fertility ok after non-alkylating chemo; alkylating chemo has dismal effect, even after limited cycles

title: Radiation Oncology/Hodgkin/Early stage


text:
Radiation Oncology/Hodgkin/Advanced stage

Advanced Stage Hodgkin's Lymphoma

Randomized

 * EORTC 20884 (1989-2000) -- MOPP-ABV, if CR -> RT vs. observation
 * Randomized. 739 patients. Stage III-IV. MOPP-ABV x 6-8 cycles depending on response. If CR after 4 cycles (early CR), received 6 cycles total. If CR at 6 cycles, received 8 cycles total. If early or late CR, randomized after completing all chemo. Arm 1) IFRT 24 Gy vs Arm 2) observation. If PR after 6 cycles, no further chemo and IFRT (not randomized) 30 Gy to nodal sites or 18-24 Gy to extranodal sites plus optional 4-10 Gy boost. CR in 57% (n=421), of these 333 (79%) were randomized.
 * Overall; 2003 PMID 12802025, 2003 — "Involved-field radiotherapy for advanced Hodgkin's lymphoma." (Aleman BM et al. N Engl J Med. 2003 Jun 12;348(24):2396-406.) Median F/U 6.6 years
 * Outcome: Randomized (n=333): 5-year EFS observation 84% vs. RT 79% (NS); 5-year OS 91% vs. 85% (NS). Local relapse RT 46% vs. 27%. Partial response cohort (n=250): 5-year EFS 79%, 5-year OS 87%
 * Second cancers: 5-year rate observation 4% vs. RT 8% (p=0.05)
 * Conclusion: No need for IFRT in patients who are in CR after MOPP-ABV; only patients in PR after chemo benefit
 * RT QC; 2005 PMID 15936157 -- "Quality control of involved-field radiotherapy in patients with advanced Hodgkin's lymphoma (EORTC 20884)." (Aleman BM, Int J Radiat Oncol Biol Phys. 2005 Nov 15;63(4):1184-90. Epub 2005 Jun 2.)
 * Major violation rate 47% (predominately target volumes). Dose correct in 81%. However, no difference in cumulative failure rate between with or without major violations
 * Conclusion: Outcome was not influenced by violations of the RT protocol
 * Partial Response; 2007 PMID 17097834 — "Involved-field radiotherapy for patients in partial remission after chemotherapy for advanced Hodgkin's lymphoma." Median F/U 7.8 years
 * Outcome (all IFRT): 8-year EFS 76% and OS 84% not significantly different from those with CR +/- RT (73-77% and 78-85%).
 * Second cancers: Comparable to non-irradiated patients
 * Conclusion: Outcomes suggest a definitive role for RT in patients with PR
 * Other publications: PMID 15936157, 2005 (Quality control)

 * SWOG 7808 (1978-88)
 * Randomized. 530 patients entered, 322 achieved CR after MOP-BAP, 278 pts randomized. Stage III-IV. Randomized to low-dose RT (10-20 Gy at 1.5 Gy/fx) to all initially involved sites vs observation. RT: 135 randomized, 104 received it, 18 major protocol violations
 * 1994 PMID 8172436, 1994 — "Low-dose involved field radiation after chemotherapy in advanced Hodgkin disease. A Southwest Oncology Group randomized study." Fabian CJ et al. Ann Intern Med. 1994 Jun 1;120(11):903-12.
 * 5-year outcomes: RFS and OS similar between the two arms. RT improved RFS for pts with NS histology (82% vs. 60%, SS) or bulky disease (75% vs. 57%, SS)
 * RT subanalysis: Relapse rate: 8% in correctly delivered RT, 16% in as-treated with RT, 23% in as-assigned to RT, 32% in CT alone
 * Conclusion: RT benefits pts with bulky disease (>6cm) or nodular sclerosing HD who achieve CR after chemo.

 * HD1 (German Hodgkins Study Group)
 * PMID 8624293 — "Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advanced Hodgkin's disease. German Hodgkins' Study Group (GHSG)." Diehl V et al. Ann Oncol. 1995 Nov;6(9):901-10.
 * 288 pts. Stages IIIB-IV. Induction with 3 cycles COPP/ABVD. If CR, then randomized to 20 Gy to involved fields (IF) or 1 additional cycle of COPP/ABVD. Pts with nodal PR received more RT: 20 Gy IF with 40 Gy to persistent disease.
 * 59% had CR after induction. No difference in relapses between those randomized to the 2 arms. 3-fold higher risk of relapse for those receiving no additional therapy (refused).

Retrospective

 * NCI, 1991 - PMID 1988570 — "Treatment of advanced-stage massive mediastinal Hodgkin's disease: the case for combined modality treatment." Longo DL et al. J Clin Oncol. 1991 Feb;9(2):227-35.
 * Retrospective. 49 pts with bulky disease (most were Stage III-IV). 10 pts received mantle field RT after MOPP, the rest received MOPP alone. Tumor mortality 80% vs 44% (nearly SS, p=0.055). OS not S.S.

 * Yale, 1995 (1969-89)
 * PMID 9166487 — "Combined Modality Therapy in Previously Untreated Patients With Advanced Hodgkin's Disease: A 24-Year Follow-Up Study." Salloum E et al. Cancer J Sci Am. 1995 Nov;1(4):267.
 * Retrospective. 186 pts. Stages IIB,III,IV. Pts received 6 months of chemotherapy (MVVPP, MOPP, MOPP/ABVD, or ABVD) followed by RT.
 * FFS was 63% @ 5 yrs, 56% / 10 y, and 40% / 23.5 y.
 * Comment: Better results than CALGB 8251 trial with MOPP alone but similar to those using MOPP/ABVD or ABVD.

 * ECOG E1492 - phase II, Stanford V chemotherapy
 * Stage I/II bulky and Stage III/IV. Stanford V x 12 weeks followed by 36 Gy RT to nodes > 5 cm.
 * PMID 10694546 (2000) — "Assessment of the stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin's disease: Eastern Cooperative Oncology Group pilot study E1492." Horning SJ et al. J Clin Oncol. 2000 Mar;18(5):972-80.

To add:
 * German HD
 * SWOG
 * EORTC-GPMC

Meta-analysis
 * 1998 PMID 9508162 -- "Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group." (Loeffler M J Clin Oncol. 1998 Mar;16(3):818-29.)
 * 14 trials, 1740 patients. 8 comparisons of CT +/- RT, 8 comparisons of CT1 vs CT2+RT
 * 10-years: addition of RT shows 11% benefit in tumor control (SS), no difference in OS. However, in CT1 vs. CT2+RT comparisons, no difference in tumor control, but OS better 8% if no RT but more chemo. Also significantly fewer fatal events in chemo only group in CR
 * Conclusion: Combined modality significantly inferior survival, if adequate chemo given
 * 2003 Comment: PMID 12788163 -- "Consolidation radiotherapy in the treatment of advanced Hodgkin's disease: is it dead?" (Prosnitz LR, Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):605-8.)
 * Good review of literature. Several issues with analysis, only 6 of the 14 studies actually published as full manuscripts. Conclusion: "Targeted low-dose consolidation RT, skillfully administered, probably does some good."

Non-randomized

 * MRC UKLG LY09 - IF-RT for incomplete response to chemo or bulky disease presentation
 * 807 pts. Prospective, randomized (chemo, not +/- RT). Randomized to ABVD or 1 of 2 multidrug combinations x 6 cycles (up to 8). IF-RT recommended for incomplete response to chemo or bulky disease presentation
 * 2010 PMID 20498402 -- "Consolidation Radiotherapy in Patients With Advanced Hodgkin's Lymphoma: Survival Data From the UKLG LY09 Randomized Controlled Trial" (Johnson PW, J Clin Oncol. 2010 July 10;28(20):3352-59.) - Median f/u 6.9 yrs
 * 702 of 807 achieved objective response. Postchemo RT given in 300 (43% of responders). ; 5-yr PFS 86% (RT) vs 71% (no RT);(HR 0.43). Overall survival, HR = 0.47.
 * Conclusion: Patients who received consolidation RT apparently had better outcomes.

 * Stanford
 * PMID 11821442, 2002 — "Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial." Horning SJ et al. J Clin Oncol. 2002 Feb 1;20(3):630-7.
 * Prospective. 142 pts. Stage III-IV (or Stage I-II if bulky). Treated with Stanford V x 12 wks followed by 36 Gy to initial sites of bulky (>5cm) or macroscopic splenic dz. Most pts received modified mantle field.
 * Median f/u 5.4 yrs. FFP 89%, OS 96%. FFP 94% (for prognostic score 0-2) vs 75% (for 3 or more).

Chemotherapy alone

 * CALGB 8251
 * PMID 1383821, 1992 — "Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD." Canellos GP et al. N Engl J Med. 1992 Nov 19;327(21):1478-84.
 * Both ABVD and MOPP/ABVD were superior to MOPP alone. ABVD less toxic than MOPP/ABVD.

 * CALGB 8952
 * PMID 12586796, 2003 — "Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial." Duggan DB et al. J Clin Oncol. 2003 Feb 15;21(4):607-14.
 * 76% CR, 63% FFP, 81% OS at 5-yrs, no difference between arms. Worse pulmonary and hematologic toxicity and more 2nd malignancies with MOPP/ABV.
 * No benefit for MOPP/ABV vs ABVD. ABVD should be considered standard regimen.

Chemotherapy comparisons

 * ABVD is currently the standard regimen (Nov 2012)
 * Stanford V is much shorter, and has lower risk of pulmonary toxicity. However, it was designed with consolidative RT, and elimination of RT does not appear feasible. When RT is given appropriately, outcomes are comparable to ABVD
 * BEACOPP may be associated with improved PFS, but has greater toxicity. Given good salvage regimens, the improved PFS may not translate into improved OS

 * Intergroup E2496 -- ABVD vs Stanford V
 * 2012 PMID 23182987 -- "Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496)." (Gordon LI, J Clin Oncol -- online before print, November 26, 2012.) -- Median f/u 6.4 yr
 * 5-yr FFS 74% (ABVD) vs 71% (Stanford V), NS. No difference in CR rate (73% vs 69%).
 * Conclusion: "ABVD remains the standard of care for patients with advanced Hodgkin lymphoma."

 * UK ISRCTN 64141244 (1998-2006) -- Stanford V vs ABVD
 * Randomized. Trial stopped early due to problems with mechlorethamine supply. 520 of target 580 patients with Stage IIB-IV, or bulky (>5cm) Stage I-IIA. Arm 1) Stanford V x12 weeks vs. Arm 2) ABVD 6-8 cycles. RT in both arms 34-36 Gy to site of bulky disease and splenic deposits; later in the trial RT in ABVD arm only if not CR. RT given in 73% of SV arm and 53% of ABVD arm
 * 2009 PMID 19738111 -- "Randomized comparison of the stanford V regimen and ABVD in the treatment of advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244." (Hoskin PJ, J Clin Oncol. 2009 Nov 10;27(32):5390-6. Epub 2009 Sep 8.) Median F/U 4.3 years
 * Outcome: 5-year PFS SV 74% vs. ABVD 76% (NS); 5-year OS 92% vs. 90% (NS).
 * Toxicity: Acute toxicity comparable; late pulmonary toxicity worse with ABVD
 * Conclusion: Efficacy of Stanford V and ABVD comparable when given in combination with appropriate RT

 * Intergruppo Italiano Linfomi (1996-2000) -- modified Stanford V vs MOPPEBVCAD vs ABVD
 * Randomized. 334 patients with Stage IIB-IV. Arm 1) ABVD x6 cycles vs. Arm 2) Stanford V x3 cycles vs. Arm 3) MOPPEBVCAD x6 cycles. Goal to decrease RT. RT given to previous bulky sites or PR but not more than 2 sites; dose 36 Gy if uCR or 42 Gy if PR. RT given in 76%, 71% and 50%.
 * 2005 PMID 16172458 -- "ABVD versus modified stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin's lymphoma: final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi." (Gobbi PG, J Clin Oncol. 2005 Dec 20;23(36):9198-207. Epub 2005 Sep 19.)
 * Outcome: 5-year PFS ABVD 85% vs. Stanford V 73% vs. MOPPEBVCAD 94% (SS worse for Stanford V); 5-year OS 90% vs. 82% vs 89%.
 * Toxicity: Myelotoxicity MOPPEBVCAD > STanford V > ABVD
 * Conclusion: ABVD best choice when combined with optional limited RT. Stanford V (as originally designed) is unlikely to allow reduction in subsequent RT

 * EORTC/GPMC
 * PMID 7509381, 1994 — "A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial." Somers R et al. J Clin Oncol. 1994 Feb;12(2):279-87.
 * Randomized to MOPP x 8 or alternating MOPPx2/ABVDx2/MOPPx2/ABVDx2. Rt was given to bulky disease (>5cm) or residual areas.
 * MOPP/ABVD led to improved response rate and failure-free survival (FFS) but no difference in relapse-free survival or OS. Early CR (CR4) is associated with final remission.

 * EORTC 20012 (ongoing) - ABVD vs BEACOPP

Patterns of failure

 * PMID 688174, 1978 — "Patterns of relapse in advanced Hodgkin's disease treated with combination chemotherapy." Young RC et al. Cancer. 1978 Aug;42(2 Suppl):1001-7.
 * 161 pts with advanced stage disease achieved CR after chemo. 32% have relapsed. Pts with higher stage, systemic symptoms, and nodular sclerosing histology most likely to relapse. 92% relapse in sites of prior disease. RT did not alter the pattern of sites of relapse.

Radiation doses

 * EORTC 20884(PMID 17097834)
 * Nodal areas - 24 Gy (if CR), 30 Gy (if PR), boost 4-10 Gy
 * Lung - 16 Gy (18 Gy if PR), boost 4-10 Gy
 * Liver - 20 Gy
 * Bone - 24 Gy, boost 10 Gy


text: Template:Radiation Oncology/Hodgkin/TOC

title: Template:Radiation Oncology/Hodgkin/TOC