Interstitial Brachytherapy For Buccal Mucosa

Introduction
Interstitial brachytherapy for buccal mucosal tumor can be used as alone or as boost following EBRT both
in primary treatment or to treat recurrent disease in properly selected patients.

Anatomic topography:
 The buccal mucosa is bounded by the lower and upper gum sulcus; anteriorly by lip commissure and
posteriorly by intermaxillary commissure.
 Lymphatic drainage is to submandibular nodes or directly to jugular nodes.
 Critical organs : mandible, the gingiva and the teeth, and soft tissues such as muscles and skin (in very
infiltrating tumours).

Indications:
 Primary tumours < 40 mm in size, involving the anterior two thirds of the buccal mucosa, without
involvement of the gingiva and intermaxillary commissura, : an "ideal" indication for brachytherapy.

 Tumours >40 mm or if radical surgery is contraindicated (tumours involving the posterior 1/3rd of
buccal mucosa without involvement of the intermaxillary commissure): EBRT f/b BT boost

Contraindications:
 Deep involvement of the gingivobuccal Sulcus(high risk of osteoradionecrosis to the mandible)
 Involvement of mandible, maxillary or intramaxillary commissura

Interstitial brachytherapy Technique:

Target volume:
 Defined by intraoral examination completed by a bidigital palpation of the tumour.
 CTV= GTV+10mm margin at anterior and posteriorly and 5-10mm above and below (limited by
anatomic constraints)
 If BT is used as boost then original volume(GTV-B) should be defined by metallic clip or tattooing or
photograph or Imaging like CT scan and/or MRI

Technique:
Two implantation techniques: Guide gutters and plastic tubes according to the tumour volume and site.

A. Guide Gutter or Hairpin Technique (Pierquin and Chassagne)

Superficial, well limited, anterior lesions, close to the lip commissure< 20 mm in size are appropriate
The guide gutters are implanted parallel to the buccal mucosa in the anteroposterior direction.

B. Plastic Tube Technique of Henschke:

 Most common method and indicated for all lesions other than those appropriate for hair pin technique.
 The number of lines, distance between the lines, number of planes and distance between the planes are
established according to the dimensions of the target volume.
 The needles are implanted through the skin: first parallel to each other, parallel to the oral mucosa and
parallel to the horizontal branch of the mandible.
 Under digital control, the lines are placed approximately 3-5 mm deep, under the buccal mucosa.
 They should cover 10 mm of normal mucosa behind or in front of the lesion with a recommended
spacing of 12 to 15 mm. Two or three plastic tubes are usually required to cover the target of thickness
<5 mm. Plastic spacers and Retention buttons at both ends keep the tubes parallel.
 If the lesion is thicker than 5 mm, a second plane of tubes is implanted between the first one and the
skin, with an interplane spacing equal to the intersource spacing in each plane.
 With a single plane, the thickness of the target volume equals about 50% of the space between the lines
(i.e. distance 18 mm, treated thickness 9 mm). If the thickness to be treated is greater, 2 planes are
necessary or the second technique should be chosen.
 A lead shield can be used to protect the mandible and superior maxilla

The loading is based on the target volume according to the rules of the Paris System. (parallel loading).
Dose prescribed:
Definitive BT: 65–70 Gy (LDR/PDR)
Brachytherapy boost after 45–50 Gy of external beam irradiation: 25–30 Gy (LDR/PDR).

Complications and follow-up:

 The GEC-ESTRO recommends regular follow-up one month after treatment, 3monthly during 1 to 3y, 6
monthly during 4 and 5y , then annually.
 The most common complication is soft tissue necrosis.
 Bone necrosis became uncommon once lead gutters were systematically employed during irradiation or
intensity modulation with a stepping source was used.
 The vast majority of necroses are managed medically with antibiotics, steroids, antalgics, mouthwashes,
and proper feeding. Hyperbaric oxygen may be useful in severe cases.
 A clinical examination under general anesthesia is recommended to resect superficial necrotic tissues
and to exclude a local relapse. Biopsies are not recommended unless tumor progression is suspected.
 Surgical excision of necrosis should only be considered after the failure of medical treatment

ISRT in Carcinoma Tongue

Introduction:
Localised Ca Tongue are ideal indication for brachytherapy because of major requirement for local control
while maintaining structure and function
Indications:
For T1 N0 and T2 N0 patients where the tumour is less than 30 mm in size, brachytherapy can be given as
the sole treatment for primary tumour. For larger tumours or those with positive nodes, combined surgery
and post operative radiation may be preferable but if this is not feasible patients should have external beam
radiation to the primary and node areas with brachytherapy as a boost to the primary.
Contra-Indications:
• Patient unfit for the procedure.
• T4 disease with bone involvement

Target Volume
 The palpable gross tumour volume plus a margin of at least 5mm all around it.
 Length of the limbs need to be long enough to adequately cover the volume ( the lower end of hairpin and
loop implants have no crossing sources as they do at the top).

Technique
Pre-planning:
 Measure the tumour carefully and plan the no. of radiation sources and lengths or dwell points and
dwell positions and their separation. This will allow a provisional dosimetry to be performed so that a
source activity can be chosen to deliver a dose rate of 40 to 50 cGy/h during the implant
 The two commonest techniques used: the guide-gutter technique and the plastic-tube loop technique

Guide-gutter technique:
Iridium wire hairpins are prepared with a fixed separation of 12 mms. This limits the width of volume
which can be treated to approximately 15 mm (appropriate for smaller tumor <30 mm in length).
The implant performed with the patient sitting upright under LA and sedation or rarely under GA .
The number and length of hairpins to be used as decided from the provisional dosimetry.
The aim is for the sources to be equidistant, parallel and straight and to cover the target volume
The first phase of the implant is performed with inactive guide gutters (inactive device) introduced into the
tongue with the help of fluoroscopy .
When guide gutter is in position they are replaced with radioactive hair-pins and same repeated for others.
Plastic-Tube Loop Technique:
 Advantages of wider separation >12cm(can treat larger volume),remote after loading technique with
less risk of exposure and less chance of local edema induced source displacement
 The number of loops, separation, length are planned beforehand as per the rules of the Paris system.
 Loop techniques are performed under general anaesthesia.
 The implant is done by creating a loop of plastic tubing which goes from the skin up over the tongue
and down through the skin again.
 Two shielding devices are systematically used in oral-cavity cancers: 1.radiotransparent device for
radiograph control and 2.Made up of lead in order to decrease the dose to the critical organs.

Dose and dose rate:

 As sole radical treatment: LDR 65 Gy prescribed to the 85% reference isodose using the Paris System.
A dose rate of 40 - 50 cGy/h aimed to achieve the best balance between local control and complications.
 As a boost : 45-50 Gy in 2 Gy fractions with external beam radiation and 20 to 25 Gy with the implant

For LDR brachytherapy the mean parameters for in the oral cavity are:
 separation 14 mm
 dose rate 40 to 50 cGy/hr
 total dose 65-70 Gy

Complications:
 Patients will get an acute mucosal reaction reaching a peak 7 to 10 days after the implantation and then
settles over the succeeding 10 to 20 days. Patients will require adequate analgesia during that period.
 The most common late complication is soft tissue necrosis.
 Bone necrosis became uncommon once lead gutters were systematically employed during irradiation or
intensity modulation with a stepping source was used.
 The vast majority of necroses are managed medically with antibiotics, steroids, antalgics, mouthwashes,
and proper feeding. Hyperbaric oxygen may be useful in severe cases.
 A clinical examination under general anesthesia is recommended to resect superficial necrotic tissues
and to exclude a local relapse. Biopsies are not recommended unless tumor progression is suspected.
 Surgical excision of necrosis should only be considered after the failure of medical treatment
 Chemoradiation In Advanced Head and Neck Cancer

Although there are a number of ways to integrate chemotherapy with irradiation, currently available data
support the concurrent integration of the modalities as the most efficacious.
In the MACH-NC analysis, the mortality risk reduction seen with concurrent cisplatin and irradiation was
threefold that seen for induction studies using cisplatin and 5-fluorouracil.138 Given proven efficacy in
patients with poor prognostic unresectable disease, more recent investigations have applied the approach in
better prognostic organ preservation and adjuvant settings.
Concurrent chemotherapy and irradiation programs vary in many ways, of which the type of chemotherapy
(i.e., specific agents, single agent or combination) and irradiation schedule (i.e., dose, fractionation) are the
most apparent variables. In general, three main approaches can be discerned: single-agent or combination
chemotherapy with continuous-course irradiation; combination chemotherapy with split-course irradiation,
often with altered fractionation; chemotherapy alternating with irradiation.148 Although continuous course
radiation may be desirable and more attractive from a radiobiologic perspective, local toxicities may
preclude it depending on the concurrent agents used. The first two approaches are the most common.
In the most recent report of the MACH-NC analysis,138 they were divided into four categories: platin plus 5-
fluorouracil; other polychemotherapy without platin; monochemotherapy with platin; other mono-
chemotherapy. All four categories were associated with significant risk reduction in mortality, with the
hazard ratios ranging from 0.74 to 0.89. That being said, platinum-based chemotherapy was associated with
the largest benefit (hazard ratio 0.75; P <.01), a conclusion shared in another meta-analysis reported by
Browman et al.149 Of interest, platin plus 5-fluorouracil (hazard ratio 0.77) offered no advantage compared
to platin alone (hazard ratio 0.74).
A three-arm study reported by Adelstein et al.150 (E1392) is consistent with the above analysis. In this trial,
295 patients with unresectable squamous cell cancer were randomized to radiation therapy alone (70 Gy, 2
Gy fractions); cisplatin 100 mg/m2 on days 1, 22, and 43 concurrent with the same irradiation schedule; or
split-course irradiation (60 to 70 Gy, 2 Gy fractions) with three planned cycles of concurrent cisplatin and
infusional 5-fluorouracil, although resection was considered after two cycles. Treatment with concurrent
cisplatin radiation yielded a significantly higher 3-year survival rate compared to radiation alone (37% vs.
23%; P = .014). Despite the added chemotherapy agent and the option of possible surgery, the split-course
arm offered no advantage in efficacy (3-year survival rate of 27%).
Although daily,151 weekly,152 and every 3-week schedules of cisplatin intravenously concurrent with
radiotherapy have been applied, the latter schedule is the one most studied and is a widely accepted
standard.
The use of concurrent chemotherapy may increase hematologic toxicity, including anemia. Since anemia
may adversely affect the efficacy of irradiation, the integration of an appropriate hematopoietic growth
factor is a consideration. In this regard, a multicenter, double-blind, randomized, placebo-controlled trial
evaluating the addition of erythropoietin 300 IU/kg three times weekly during postoperative radiotherapy is
of interest.158 Three hundred and fifty-one patients with squamous cell head and neck cancer were
randomized to erythropoietin or placebo starting 10 to 14 days before and then concurrently with 60 to 70
Gy of radiation. Although target hemoglobin levels were reached in 82% of patients receiving
erythropoietin compared to 15% receiving placebo, locoregional progression-free survival (adjusted relative
risk 1.62; 95% confidence interval, 1.22 to 2.14; P = .0008), locoregional progression (relative risk 1.69;
95% confidence interval, 1.16 to 2.47; P = .007), and survival (relative risk 1.39; 95% confidence interval,
1.05 to 1.84; P = .02) were all inferior on the erythropoietin arm, raising concerns that disease control may
be adversely affected with concurrent use of the growth factor.
An important question is whether the use of newer, more efficacious, altered fractionated irradiation
programs159 obviates the benefits accrued with the addition of chemotherapy. In a randomized study
reported by Jeremic et al., the addition of daily cisplatin to hyperfractionated radiotherapy also lead to
incremental benefits. The results of these studies are consistent with the MACH-NC analysis, which
demonstrated significant hazard ratios consistent with benefit among patients receiving postoperative
irradiation (hazard ratio 0.80), conventional radiotherapy (hazard ratio 0.83), or altered fractionated
radiotherapy (hazard ratio 0.73) suggesting that the benefit of adding concomitant chemotherapy was found
regardless of the type of irradiation applied.
For patients who are not cisplatin candidates, using a carboplatin-based (e.g., carboplatin/5-fluorouracil)162
or other concurrent programs that have withstood the scrutiny of a randomized trial is recommended. A
newly available option is cetuximab and concurrent irradiation, which was shown in an important proof of
principle trial to be superior to radiotherapy alone.163 Patients with locoregional advanced head and neck
cancer were randomized to radiotherapy alone (213 patients) or combined with cetuximab (211 patients);
median follow-up was 54 months. The initial dose of cetuximab was 400 mg/m2 followed by 250 mg/m2
weekly for the duration of radiotherapy. The median duration of survival was 49 months after combined
therapy compared with 29 months after irradiation alone (P = .03). Further, the addition of cetuximab was
associated with significantly improved progression-free survival (P = .006). Other than an acneiform rash
and infusion reactions, grade 3 or greater complications were similar in the two groups of patients.
Choosing among the numerous concurrent programs can be difficult. The NCCN recommended five drug
programs for concurrent use with radiotherapy in their treatment guidelines: cisplatin; cisplatin/5-
fluorouracil infusion; cisplatin/paclitaxel; hydroxyurea/5-fluorouracil; and carboplatin/5-flurouracil.146 To
this list, cetuximab is appropriately added. It is important to emphasize that treatment with concurrent
chemotherapy and irradiation may be associated with significant toxicity; treatment-related mortality, albeit
infrequent (less than 5% in the cooperative group setting), may occur. Appropriate infrastructure, an
experienced multidisciplinary team, and a cooperative patient are necessary to optimize both efficacy and
safety.