Linear Accelearator Construction

Definition: It is a device that uses high frequency electromagnetic waves to accelerate charged particles, such as electrons to high energies through a linear tube.

Types of linear accelerator design:

1. Standing wave design
2. Traveling wave design

In the latter design there is a dummy load, which absorbs the excess power and prevents a reflected wave. In the standing wave design, there is reflection of the waves at both the ends of the structure, so that combinations of forward and reverse directed waves give rise to a standing wave design.

Principle:

Whether standing or traveling wave design linear accelerators used in medical purposes, accelerate electrons along electromagnetic waves or frequency in the microwave region that is around 3000 Hz.

Components of a linear accelerator:

1. The Magnetron

2. The Klystron

3. Accelerator tube

4. Gantry & treatment head:

a. Transmission target

b. Flattening filter, and scattering foil.

c. Dose monitoring chambers.

d. Collimators:

i. Photons

1. Primary collimator.

2. Secondary collimators

3. Multileaf collimators.

ii. Electrons

History:

The first medical linear accelerator was installed in the Hammersmith Hospital in United Kingdom, and Henry Kaplan was the first person to use it in Stanford in USA.

Description of each component:

1. D. C. power source is an independent power source for the machine.
2. The Moderator generates pulses off high-voltage direct current for both the Electron gun, and the Magnetron at the same time.
3. The electron gun consists of a metal filament and electrons are emitted by the principle of thermionic emission. The electrons have a energy of 50 KeV.
4. The Magnetron is a device, which generates microwaves.
1. Principle: In order to generate these microwaves, electrons are emitted from a cathode filament. A DC electric field is applied between the cathode and the anode while the static magnetic field is applied perpendicular to the plane of cross section of the cavities. Under the influence of the pulsed DC field, electrons are accelerated. Simultaneously due to the magnetic field, they begin moving in complex spirals.
2. Each Magnetron is a cylindrical structure containing a central cathode and an outer anode, with resonant cavities inside. As the Electron spiral into these cavities, they radiate microwave pulses.
3. Each microwave pulse has a frequency of 3000Hz.
5. The Klystron is a microwave amplifier. It needs a microwave oscillator to function.
1. Principle: An electron stream being accelerated across a potential difference is intercepted by a microwave beam. The electron velocity gets altered and these are separated into bunches. The electron bunches enter a cavity where they induce a charge which slows them down. As the electrons slow down they loose energy by radiation which is radiated as microwaves.
2. The high powered microwaves are then injected into the accelerator tube via the wave guide where they are used to set up a electromagnetic field.
6. The Accelerator tube is a long tube made of copper with diaphragms with holes where an electromagnetic wave is setup from the klystron / magnetron and electrons generated from the gun are accelerated. The principle is akin to the surfers of waves in ocean. The electron beam generated is usually of 3mm diameter.
7. The treatment head is the heavily shielded part of the machine where the electron beam or photon beam exits the machine and it contains:
1. Bending Magnets: Allow the electron beam to be bent at 90 or 270 degrees prior to striking the transmission target
2. Transmission target: Made up of a heavy metal where high speed electrons strike and generate an x-ray beam. The transmission target also “hardens” the beam by removing all the low energy photons. It is called a transmission target as all photons are passing through the target before emerging out.
3. Flattening filter: The beam emitted from the target is forward peaked and a flattening filter is placed in the pathway to ensure that the beam is flat across the field.
4. Dose monitoring chambers: Are special sealed ion chambers which monitor the:

i. Dose rate

ii. Integrated dose

iii. Field symmetry.

5. Scattering foils: Allow the thin electron pencil beam to be scattered using thin lead films so that a useful beam can be obtained.
6. Collimators: 4 types of collimators exist :

i. Primary Collimators: Where the beam is shaped into the useful size and unwanted photons are removed.

ii. Secondary Collimators: Allow customized shaping of the beam by two pairs of movable lead blocs which move in a fashion such that the edge is always parallel to the beam. The maximum field size is 40 x 40 cm when projected at the isocenter.

iii. Multileaf collimators.

iv. Electron Collimators: Are special devices called electron cones used to generate the electron field shape. These are usually attached to the machine externally.

7. Light localization system: Allows a visual reference to the x ray beam being generated.
8. Secondary trays: Allow mounting of accessories like shielding blocks and wedges underneath the treatment head.
7. Gantry: This entire assembly is mounted on a gantry which is usually isocentrically mounted i.e. the axis of rotation of the gantry, couch and collimator pass through the same point.

My Review of Palm LifeDrive Handheld

Originally submitted at ShopLocal

Palm LifeDrive Handheld

Excellent when it works.

By Santam Chakraborty from Chandigarh, India on 10/28/2007

 

4out of 5

Pros: Compact Design, Great Software Bundle, Easy To Use, Fast, Additional Software, Adequate Storage

Cons: Limited Compatibility, Bulky Design, Lack of Linux Support, Heavy

Best Uses: Reading ebooks, Organization, Databases, Business Use, Medical Calculators, Listening to music, Multimedia

Describe Yourself: Doctor, Tech Savvy, Radiation Oncologist

Primary use of this product: Personal

I have used this palmtop for the past one year to listen to music on the go and also to keep an mobile library of books for ready reference during travel and while at work. It has a great storage and obviates the need to buy another memory card. I also used it as a 4 GB USB drive and a storage for photos and videos taken from digital cameras. The great thing about this is the great storage and the wide screen. The palm was however a tad on the slower side on switching applications and of course the battery was not too great. In fact after one and half years of rather heavy use the battery is defunct.

Palm Life Drive with iSilo

Tags: Picture of Product, Using Product

Using the stylus

Tags: Made with Product, Picture of Product, Using Product

(legalese)

Beam Directed Radiotherapy

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Interaction of Radiation with matter

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Beam Modification In Radiotherapy

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Radiation Protection in Radiotherapy

Radiation Protection

From: santam, 13 minutes ago

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Here is a seminar on radiation protection that deals with various topics like radiation protection principles like ALARA, dose limits, MPD , design of radiation facility and history of the issue.

SlideShare Link

3D CRT and IMRT in the management of Cervical Cancers

Introduction:

Three dimensional conformal radiation therapy (3D CRT), and it's more recent modification Intensity Modulated Radiation Therapy, together represent one of the most significant developments in the delivery of external beam radiation therapy that have happened over the past one decade. Three dimensional conformal radiation therapy has been defined by Dr S. Webb as “A technique that aims to exploit the potential biological improvements consequent on better spatial localization of the high-dose irradiation volume”. Intensity Modulated radiotherapy (IMRT) is a special form of three dimensional conformal radiation therapy where the intensity (or rather the fluence) of the beam is modified across the beam with the use of some beam modifying device in order to give better conformality. Taken together, both the techniques rely heavily on the use of various volumetric imaging techniques and advanced planning systems, made possible practical, thanks to the rapid and universal availability of cheap computing power. Cervical cancer being the most common gynecological cancer, with it's unique position of being curable in a large proportion with radiation therapy, obviously forms a attractive target for these new techniques of external beam radiation therapy.

Principle:

The basic principle behind the use of conformal radiation therapy is target delineation followed by planning to accommodate that target within a closely fitting (conforming) high dose envelope while at the same time using multiple individually designed beams to limit the surrounding dose spillage to the normal tissues. The nature of radiation beam itself is the most serious impediment to attainment of better conformality, with it's properties of entrance and exit dose and a continuously decreasing dose deposition across the length of the beam. The basic rationale behind the use of multiple beams is to divide the total dose to be delivered into smaller fractions directed at different angles at the target, so that the highest dose is localized to the area where the beams cross each other with a rapid dose falloff towards the periphery of the targeted volume. In IMRT the planning process is taken one step ahead with simultaneous modulation of the intensity of the beams to generate the most conformal dose distribution possible.

The target volume for external beam radiation therapy in carcinoma cervix includes the cervix uteri with it's gross disease extension, the soft tissue surrounding the uterus and the adenexa (parametrium) along with first echelon of the draining nodes. External beam radiation therapy is usually combined with brachytherapy so that a biologically equivalent dose of 55 - 60 Gy is delivered to the whole pelvis, with a higher dose to the cervical target volume (80 -85 Gy in early stage disease and a dose of 85 -90 Gy in advanced disease).

Indications:

The role of these two techniques thus needs to be defined for two separate scenarios:

1. Where the target volume is being treated with external beam radiation therapy: This is the treatment of choice for many of the cervical cancers in our country. The radiation therapy in this situation is delivered with a combination of external whole pelvic radiation followed with a boost to the central disease with brachytherapy. Many other combinations of external beam radiation and brachytherapy are in use along a myriad of dose and fractionation schedules.

2. Where the target volume has been treated with the use of definitive surgery and the role of radiation therapy is to look after microscopic (or sometimes gross) residual disease.

In both of these scenarios the target volume for cervical cancer is bowl shaped, with the bowl walls following the pelvic walls and the base being formed by the central disease component. Through this “bowl” shaped target volume pass various structures like the rectum, bladder and sigmoid colon. The loops of the small intestine lie inside the bowl and in closer proximity to the base of the bowl in the postoperative patient. The conventional four field technique of external beam radiation therapy aims to encompass this bowl inside a large “box” shaped dose distribution. IMRT in this respect has the advantage that it allows dose sculpting so that the cumulative dose delivered is shaped to conform to this “bowl's” base and walls, containing the uterus, cervix and paracervical tissues, with maximal sparing of the “central contents” (ie. sigmoid colon, small intestines). Therein lies the true advantage and also the Achilles heel of the technique. Although the indications of IMRT are being defined, several potential applications of these techniques become readily apparent:

1. For irradiation of the whole pelvis: The advantage of the technique lies in better sparing of the pelvic contents from the high dose envelope. This indication is the one where the role of IMRT is being explored the most. The organs being spared include the bladder, sigmoid colon and small intestine along with the peripheral “organs” surrounding the target volume like the pelvic bone marrow and the femoral head.

2. For definitive of irradiation of the pelvic disease along with irradiation of the para-aortic nodes in patients with microscopic or gross disease in this area (Extended field radiation). The advantage of using IMRT in this scenario are two fold:

   1. Delivery of a higher dose to the gross disease in the para-aortic nodal disease.

   2. Significant sparing of the small bowel and the kidney during the process.

3. For irradiation of the residual disease in the pelvis after initial external beam radiation therapy especially when intracavitary brachytherapy is not feasible technically. The objective of IMRT in this scenario is to escalate the dose to the gross disease with a dose distribution mimicking that of brachytherapy.

4. As an alternative to brachytherapy using applicator guided IMRT, again the objective being to replicate the brachytherapy dose distribution.

5. For irradiation of recurrent disease with better confinement of the high dose region.

Planning Process:

The planning of the patient for IMRT begins with volumetric image acquisition in the treatment position. Contrast enhanced CT (CECT) scans are the baseline imaging modality with additional bowel and rectal contrast being added as necessary. For better target delineation an MRI allows a better target delineation of the primary tumor, it's parametrial extensions and pelvic lymphadenopathy. The use of biological imaging modalities like Positron Emission Tomography (PET) registered to a CT scan may allow better definition of the volumetric target volume. The use of PET-CT also allows the treating physician to delineate areas of tumor which are suspected to harbor more radio-resistant cell populations like hypoxic cells (⁶⁰Cu-ATSM PET) or proliferating cells (¹¹C -Methyl Methionine), and target them with a higher dose of radiation.

The next step ie. target delineation is the most critical step which determines the success and failure of these advanced conformal techniques. Delineation of the gross disease volume (GTV) is enhanced by the use of MRI and PET scans but clinical examination forms a very vital part of the planning process with some features of the disease process like vaginal mucosal involvement being best defined by the clinician only. Two sets of GTV need to be defined – GTV_T which includes the central disease component along with the parametrial, vaginal and uterine extensions, and the GTV_N which includes the nodal disease. Noteworthy is the fact that the GTV_T for patients being planned with definitive whole pelvic radiation forms the HR-CTV at the time of brachytherapy.

The CTV for the disease will depend on the indication for which IMRT is being delivered. Delineation of the nodal basin has been the subject of two well written reviews by Taylor and Chao and these guidelines give the treating physician guidelines for delineation of the nodal volume of CT images according to well defined vascular and bony landmarks. Separate guidelines for delineation of the para-aortic nodal volume also exist. The CTV for the patients being treated after an initial course of external radiation therapy includes the pretreatment gross cervical disease. Of note here is that IMRT can allow the treating physician to treat eccentric residual disease, parametrial disease and pelvic nodes also in this situation all of which are poorly treated using traditional intracavitary brachytherapy.

The PTV margins are a safety precaution for the setup inaccuracy inherent in delivery of fractionated external beam radiation therapy. Of note is the fact that the PTV is a composite of two broad types of uncertainties – the ITV (Internal Target Volume) which accounts for target (and normal tissue) motion and the SM (Setup margin) which accounts for the interfraction and intrafraction setup errors.

In addition to the target volume the normal organs like the bladder, rectum, sigmoid colon, urethra and the femoral heads are contoured. The small intestine being mobile needs to be contoured as a organ at risk volume which includes the entire peritoneal cavity. Normal organs need to be contoured at least 1 -2 cm above the delineated PTV. Separate PORV (Planning Organ at Risk Volumes) may need to be defined depending on the clinical setting.

The treatment prescription should not only include a statement for the dose, fractions and total time but also a statement regarding the desired quality of coverage. The modern day treatment planning systems limit us to description of a physical dose prescription but it is anticipated that in the near future prescriptions will include a statement on the biological dose coverage too. In addition to the desired target dose normal organ “constraints” need to be defined. These are usually based on the data of Emami et al but it is expected that with ubiquitous availability of CT based planning a better set of NTCP (Normal Tissue Complication Probability) against the volumetric dose volume parameters can be obtained. It is noteworthy that cervical cancers have the unique privilege of arising in a site where tumor bearing normal tissues have a significantly higher radiation tolerance than the surrounding organs.

Inverse or forward planning is done according to various algorithms based on these dose constraints. IMRT generally involves inverse planning to practically generate the complex intensity modulated field. The process of optimization of the plan using inverse planning is still iterative and time consuming at the present moment. However the use of multicriteria optimization may ease this process significantly in the near future. The calculation of the dose distribution is done using several algorithms and it is expected that in the coming years commercial Treatment Planning Systems will come with ability to calculate the dose distributions using Monte Carlo algorithms which have been shown to be consistently more accurate than the traditional methods.

Prior to the treatment verification of the dose distribution is mandatory especially if IMRT is being planned. Verification typically involves absolute and relative dosimetric checks in a phantom. Absolute dose variations of ≤ 3% and relative dose variations upto 5% are acceptable.

The actual treatment delivery can be done using several methods like compensator based IMRT, Jaw based IMRT etc. However modern day machines typically use Mutileaf collimators for ease of use and better reproducibility. It is important to understand the MLC configuration of the individual machine as that can influence and restrict the planning process significantly.

As the Achilles heel of conformal radiation therapy is the conformal dose distribution, regular checks on the setup accuracy are needed. In addition to minimize positional inaccuracies a consistent bladder and rectal filling pattern is desired. The most basic level of this check involves regular biweekly or even more frequent electronic portal images. However more recently widespread availability of sophisticated on board imaging facilities have allowed us to visualize, predict and control the setup uncertainties even more rigorously. Tomotherapy and Robotic IMRT will hopefully allow us to do this with greater precision, however the prohibitive cost limits their use in the developing countries.

Conclusion:

Conformal radiation therapy holds a great promise in the management of cervical cancers. With proper use these modalities hold the potential to improve the control and reduce the normal tissue toxicity significantly. It is particularly so for cervical cancers where radiation therapy remains the main treatment for a significant majority. However practitioners must be aware that routine implementation of these techniques will require significant capital, education and manpower investments which may be beyond the reach of most of the developing nations at the present moment.

A review of Brachytherapy in head and Neck cancers

Here is a small review of brachytherapy in head and neck cancers that I wrote for a recently concluded conference.

Brachytherapy for Head and Neck Cancers

Dr S.C. Sharma and Dr S. Chakraborty

Department of Radiotherapy and Oncology, Regional Cancer Center, PGIMER, Chandigarh

Squamous cell carcinomas of the head and neck region present an unique challange to the radiation oncologist because of the close relationship of various structures in the region responsible for maintaining the aero-digetive functions of the body along with the inherently complex topography. The area begins at the vermilion border of the lip and extends posteriorly upto the pharynx . Superiorly it is limited by the nasopharynx and inferiorly continues into the thorax via the cervical structures. The mucosal lining is the site for origin of the majority of malignancies and it is served by an extensive system of lymphtics draining into various lymphatic groups of the neck, often with extensive contralateral drainage. Majority of malignancies originating in this area are squamous cell carcinomas which are moderately radiosensitive, spread through the lymphatics and by local invasion; with the exception of few undifferentiated carcinomas of the nasopharynx which are highly radiosensitive and have significant hematogenous spread.

Brachytherapy, the most conformal form of radiation therapy, provides the best therapeutic ratio in this senario (Table 1). The unique dosimetric characterisitcs of the sealed radioisotopes used, have allowed the practising radiation oncologist to give a high dose of radiation to the tumor bearing tissue while sparing the adjacent critical structures at the same time. The functional and cosmetic outcome of brachytherapy cannot be equalled by even the most conservative of surgeries or external beam radiotherapy. Brachytherapy also allows the oncologist to deliver curative doses of radiation to the tumor in a substantially shorter period of time as compared to external beam radiation therapy, amplifying the biological response in the process. In addition it eliminates errors due to setup inaccuracies to a significant extent and thus can minimize the irradiated volume by reducing the Planning Target Volume (PTV). All these characteristics make brachytherapy the ideal form of radiation therapy both biologically and physically. However the same advantages of conformality and high dose gradient around the irradiated volume, also limit the potential application of brachytherapy to small tumor bearing regions only. The skill of acheiving an optimal geometric coverage of the target volume is also one which is acquired through experience and practice.

Table 1: Advantages and disadvantages of brachytherapy

Advantages of Brachytherapy

High dose can be delivered in a short period of time. Rapid dose fall off towards the periphery allows excellent normal tissue sparing. Increased cure rates due to a higher biologically effective dose. Decreased volume of tissue irradiated as compared to external beam radiation leading to reduction in integral dose. Elimination of setup errors as the sources maintain fixed relationship to the target volume. Better cosmetic results due to reduced volume of tissue exposed to high dose of radiation. Acute radiation reactions are sharply localized and usually occur after treatment completion – thus treatment interruptions due to acute reactions are uncommon and radiation morbidity is limited.

Disadvantages of Brachytherapy

Usefulness primarily in leisons with small size in easily accessible areas. Chance of geographic miss high if not used properly. Nodal disease can't be covered simultaneously. Quality of implant is operator dependant. Invasive procedure often requiring anaesthesia.

Almost immediately after the path breaking discovery of Radium by the Curie couple in 1898, radiation oncologists had started using radium in the management of a variety of leisons encountered in the head and neck region with mixed results. This was in a large part consequent to large degree of empiricism in the design of the treatment schedules and doses delivered at that time. This aspect was reversed after the First World War when several of the leading institutions practicing brachytherapy in Europe distilled their experience and knowledge into so called “Schools of Brachytherapy”. Notable of these were the RadiumHemmet in Stockholm (1914) , the the Radium Institute in Paris by Regaud and Lacassagne (1919). However the most influential of these Schools was the Manchester School popularised by Paterson and Parker during the 1930s using Ra²²⁶. The specification of dose prescription points and volumes, radioisotope used and desirable implant geometry went a long way in standardizing brachytherapy. Perhaps the most important contribution of these systems was that the geometry of the implants designed using these system had a near optimal distribution with minimal hot and cold spots. This was important in an era where sources were primarily preloaded and optimization of the implant was not possible after the sources had been implanted. The invention of techniqes for production of artificial radionuclides in 1935 by Irene Curie allowed the development of a widely used system of brachytherapy known as the Paris System (Pierquin, Chassagne and Dutreix) using wires or ribbons of Ir¹⁹². The use of this form of source introduced new possibilites for implantations as a result of their flexibility and adaptability.

Traditionally brachytherapy has been classified based on dose rate as low dose rate brachytherapy (Dose rate 0.4 -2 Gy per hour; classically 50 – 60 cGy /hr), medium dose rate brachytherapy ( Dose rate 2 – 12 Gy per hour) and high dose rate brachytherapy ( Dose rate 12 Gy per hour or more). Low dose rate (LDR) brachytherapy involves the used radioactive sources with low specific activity like Radium (Ra²²⁶), Cesium (Cs¹³⁷) and Iridium (Ir¹⁹²). Clinical experience with this form of brachytherapy is extensive, spanning over a century. Low dose rate brachytherapy is also considered radiobiologically superior to the other forms of brachytherapy. The reason lies in the differential repair kinetics of the tumor and the normal cells. The repair half life for normal tissues (t_1/2 = 1.5 hrs) is lesser than that for tumors so giving a continuous low dose radiation allows healing of the radiation induced subleathal damage during the course of the radiation itself so that the therapeutic ratio between cell kill and normal tissue damage becomes more favourable. Despite the results produced by HDR brachytherapy, LDR brachytherapy is still considered potentially less toxic when it is necessary to reach the limits of the normal tissue toxicity for maximizing tumor control for example definitive treatment of small cancers of lip and tongue using brachytherapy alone.

The other extreme of therapy is HDR brachytherapy, using specially designed high activity, sealed radioactive sources like Ir¹⁹² and Co⁶⁰. HDR brachytherapy has allowed the radiation oncologist significant flexibility in planning the procedure and being an afterloading technique has eased radiation protection issues simultaneously. The small source diameter allows use of thinner channels, minimizing tissue trauma and facilitating application in difficult areas like the base of tongue and nasopharynx. The higher dose rate allows quick treatment, minimizing patient discomfort and allowing OPD based treatment unlike LDR brachytherapy where the treatment often took 6-7 days. The high dose rate however negates the biological advantage of LDR brachytherapy and therefore the treatment has to be administered in fractions. This actually has lead to a protraction of treatment time and a resultant increase in the overall treatment time for majority of head and neck cancer patients. Further the total dose delivered has to be “corrected” i.e. reduced in order to avoid excessive late toxicity. The exact magnitude of this correction remains an area of controversy with various experts recommending values between 45- 55% of the LDR doses. The dose per fraction is another contentious area and it has been observed that doses higher than 4.5 Gy per fraction in the head and neck region often lead to unacceptable rates of tissue necrosis. However some areas like the lip allow the delivery of higher doses per fraction owing to the limited volume of irradiated tissue and the higher radiation tolerance.

The diverse anatomy of the head and neck region has spurred the development of several types of applicators for delivery of radioactive sources inside the tissue intersitium (Interstitial Brachytherapy). The original Manchester system advocated the use of needles containing Ra²²⁶. These needles were available in different source strengths and implantation rules were designed to load a larger amount of radium to the periphery of the implanted volume with a aim to maximize the dose homogenity(± 10%). Later on with the introduction of the Ir¹⁹² wires, several other devices were introduced to facilitate manual afterloading. Examples include guide gutter for implantation of tongue and hypodermic syringes for the lip. Another special type of applicator used for areas like the buccal mucosa and palate was surface moulds where radioactive sources were placed on a platform at a fixed distance from a superficial tumors. The complex anatomy of the nasopharynx prompted the development of a new type of intracavitary brachytherapy using specialized catheter based applicators like the Rotterdam applicator. Due to the ease of use and flexibility offered, most of the modern day interstial implants are done using plastic catheters which are introduced under the guidance of hollow needles. The various forms in which brachytherapy can be used in different sites in head and neck region are detailed in Table 2.

Table 2: Types of Brachytherapy used in Head and Neck Region

Type	Location
Interstitial	Lips, Buccal Mucosa, Tongue, Tonsil, Soft Palate, Base of Tongue, Floor of mouth
Intracavitary	Nasopharynx, Maxilla
Surface Mould	Lip, Angle of mouth, Alveolus, Hard Palate, Pinna, Scalp
Intraluminal	Post cricoid

Brachytherapy can be delivered in several situations and in combination with other forms of therapy. In majority of the areas like the tongue, buccal mucosa and oropharynx brachytherapy is used as a adjuvant to external beam radiation. External radiation is delivered to a dose of 40 – 50 Gy over a period of 4-5 weeks followed by brachytherapy. This approach allows sterilization of the microscopic disease burden surrounding the tumor and also reduces the tumor volume helping to limit the implanted volume. The high chance of occult contralateral and ipsilateral neck node metastatsis also makes this a sensible policy. However the pretreatment volume should be clearly recorded as this volume is always implanted regardless of the size of the tumor at the time of brachytherapy. The dose of brachytherapy in this situation is 20 - 30 Gy by LDR (or equivalent by HDR) and brachytherapy should be started as soon as possible – ideally within 1-2 weeks. Results of LDR and HDR brachytherapy with EBRT in various sites are detailed in Table 3 and 4 respectively.

Table 3: Results of combined LDR Brachytherapy and EBRT

Series	Year	N	Site	Outome
Gerbault(1)	1992	269	Tongue	LC 49% ; 5 yr DFS 30%
Pernot(2)	1992	147	Tongue	LC 51% ; 5 yr DFS 35%
Shibuya(3)	1993	370	Tongue	LC 48%
Decorix(4)	1984	114	FOM	LC 57% ; 5 yr DFS 16-18% (T3-T4)
Bolla(5)	1983	239	FOM	LC 81% (T1) – 37% (T3); 5 yr DFS 65% - 30%
Gerbaulet(1)	1994	80	Buccal Mucosa	LC 52% (T1 -T3) ; 5 yr DFS 31%
Pernot(6)	1994	343	Tonsil	LC 80% ; 5 yr OS 53%
PGI*	1990	157	All Sites	T1 -T2 5 yr LC 86%

DR = Dose Rate; LC = Local Control; OS = Overall Survival; FOM = Floor of Mouth; * = unpublished

Table 4: Results of HDR brachytherapy after EBRT

Author (Yr)	Site (N)	EBRT	HDR	Results
Nose (2004)(7)	Oropharynx (83)	46 Gy	21 Gy / 3.5 # / 2 days	2 yr LC 89% (T1/2); 66% (T3/4) 2 yr OS 88% (T1/2); 64% (T3/4)
Chen (2007)(8)	Oropharynx (97)	50 Gy	24 Gy (median)	5 yr LC 83% - 64% (T1 -T4) 5 yr OS 55%
Nagy-Takaesi (2004)(9)	BOT (37)	50 – 60 Gy	18 – 28 Gy	4 yr LC 60%; OS 46%
Kakemoto (2003)(10)	Tongue (14)	12.5 – 60 Gy	32 – 60 Gy / 8 -10# / 5 - 7 days	5 yr LC 71%
PGI*	Tongue , lips	40 – 50 Gy	18 -24 Gy / 5-6 # / 3 days	Immediate LC 72%

EBRT = External Beam Radiotherpay;BOT = Base of Tongue; * = Unpublished

In selected areas like the lip, early tongue cancers (<> 5 mm distant from the mandible) brachytherapy can be used alone for the entire treatment. Evidence points that for these leisons brachytherapy may provide a better cure rate with lesser toxicity as compared to EBRT or EBRT with brachytherapy. Data from investigators like Mazeron, Gerbaulet etc. show that local control rates can be as high as 80 -90% in these situation, with minimal late toxicity. In particular the latter author has shown that using brachytherapy as the sole modality can almost double the local control rates for smaller leison of the oral tongue. When brachytherapy is used alone, doses of 66 – 70 Gy LDR equivalent are delivered to the primary tumor (GTV) with a safety margin which includes the potential area of microscopic spread (CTV). The margins choosen vary according to location, type of tumor and personal experience of the investigator concerned, but usually margins of 1-1.5 cm are choosen with care to avoid the mandible as far as possible. HDR doses need to be suitably corrected and the doses delivered usually range from 40 – 50 Gy in 3 – 4 Gy per fraction treating twice daily with a suitable interfraction interval (6 hours or more). Selected series of LDR and HDR brachytherapy alone in various sites are detailed in Table 5 and Table 6 respectively.

Table 5: Selected results of LDR Brachytherapy alone

Series	Year	N	Site	Outcome
Gerbaulet(11)	1978	316	Lip	95.8% 5 yr LC (T1 - T4)
Mazeron(12)	1983	1896	Lip	96.6% 5 yr LC (T1 - T4)
Van Limbergen*	1993	2794	Lip	94% 10 yr LC (T1 – T4)
Decorix(13)	1981	602	Tongue	76% 5 yr LC; DFS 80% (T1) – 25% (T3)
Pernot(2)	1992	147	Tongue	90% LC , 62% 5 yr DFS in T1
Lefebvre(14)	1994	146	FOM	91% LC (T1) – 53% (T3); 46% overall DFS
Gerbaulet(15)	1985	266	Buccal Mucosa	LC 81% ; DFS (64%)

FOM = Floor of Mouth;DFS = Disease Free Survival; LC = Local Control; DR = Dose rate

Table 6: Results of HDR brachytherapy alone in various sites

Author	Site (N)	HDR dose	Results
Guinot (2003)(16)	Lip (39)	40.5 – 40 Gy / 8 -10 # / 5 -7 days	5 yr LC – 88% ; CSS - 90%
Kakimoto (2006)(17)	Tongue (71)	54 – 60 Gy / 9 -10 # / 5 -7 days	5 yr LC – 85.9% ; OS - 80.3%
Lueng (2002)(18)	Tongue (19)	55 Gy / 10 # / 6 days	5 yr LC – 94.7%
Inoue (2001)(19)	Tongue (25)	60 Gy / 10 # / 1 week	4 yr LC – 87%
Yamazaki (2003)(20)	Tongue (58)	48 – 60 Gy / 8-10 # / 6 -7 days	5 yr LC – 84%
PGI*	Tongue	35 -42 Gy/ 10 -12 # / 6-7 days	4 month LC - 72%

LC = Local Control; OS = Overall survival; CSS = Cause specific surviavl; * = Unpublished

A special case of brachytherapy is that for nasopharyngeal cancers where commonly the technique popularised by Lavendag is used. The procedure is commonly indicated for boosting the nasopharynx selectively after completion of EBRT to a dose of 60-66 Gy provided there is a small residual disease confined to the nasopharynx (pretereatment T1 -T3) without parapharyngeal extension and nodal disease. A dose of 18 Gy in 6 fractions over 3 days (2 fractions per day, 6 hours apart) by HDR is recommeded. The risk of late neurotoxicity and nasal synachie should be kept in mind while planning this form treatment.

Superficial (less than 0.5 cm thick) tumors of the head-and-neck areas can be treated with brachytherapy using molds. Suitable sites for mold therapy include scalp, face, pinna, lip, buccal mucosa, maxillary antrum, hard palate, oral cavity, external auditory canal, and the orbital cavity after exenteration. A total dose equivalent to about 60 Gy LDR (prescribed at 0.5 cm depth) is recommended. Brachytherapy can also be used as a boost to 45 to 50 Gy EBRT, in which cases the doses are appropriately reduced to LDR equivalent doses of 15 to 30 Gy. Moulds should be prepared from a tissue equivalent material which can be easily moulded to the surface topography like dental acrylic or perspex.

Brachytherapy can be combined with surgery in various ways the most common situation being a planned neck dissection after the completion of brachytherapy. This is most commonly used for small leisons of the tongue or oropharynx where the risk of occult nodal metastatsis may be as high as 30%. Post operative brachytherapy is rarely indicated except in senarios where gross residual or recurrence is documented and EBRT can't be delivered safely. Most commonly this situation arises after resection of a recurrent tumor in a previously irradiated area. LDR brachytherapy doses of 50 to 60 Gy have for several decades been used for the treatment of patients with recurrent head-and-neck cancer, with 30–70% salvage rate and 30–40% complication rates. For HDR brachytherapy recommended doses range from 3–4.5 Gy per fraction in 8–18 fractions.

A more specialized application of brachytherapy is the use of Intraoperative brachytherapy (IOHDR) in paranasal sinuses and and other deep areas near the base of the skull are difficult to treat either by conventional brachytherapy or intraoperative (electron beam) radiation therapy(21). After maximal resection, the tumor bed is irradiated using surface applicators placed on the tumor bed. The advantages of IOHDR include ability to displace or shield normal tissues during the irradiation and its applicability in narrow, deep cavities.The ABS recommends 10–15 Gy IOHDR in conjunction with 45–50 Gy external beam irradiation for the treatment of microscopic disease in previously unirradiated patients. IOHDR alone (without supplementary EBRT) for recurrent tumors has achieved poor local control. The IOHDR dose is to be prescribed at 1 cm from the plane of catheters (0.5 cm from the applicator surface). This provides an additional advantage that a higher dose (up to 200%) can be given at the surface (i.e., the tumor bed or surgical margin at greatest risk of harboring residual microscopic disease).

Complications of brachytherapy depend to a significant extent on the volume irradiated and the dose inhomogenity. Transient soft tissue necrosis can be expected in 15 -20% patients which usually resolves spontaneously. In case of lip mild depigmentation and telengiectasias can be expected in 10 -15% patients. The incidence of Grade 3 cosmetic sequale was estimated to vary from 1 – 9% depending on the volume irradiated. Mandibular osteoradionecrosis can occur in 5 – 10% patients and if the area is 1 cm² then majority heal with conservative management. Unlike EBRT neural and salivary gland toxicity are unknown.

To conclude brachytherapy in it's various forms remains a excellent tool for acheiving control and cure for locally confined head and neck cancers. The high degree of conformality cannot be equalled even by modern day EBRT techniques like IMRT and IGRT. However proper patient selection, experience and skill are of utmost importance in ensuring the best outcome.

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