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Two-piece customized mold technique for high-dose-rate brachytherapy on cancers of the buccal mucosa and lip

Published:October 10, 2011DOI:https://doi.org/10.1016/j.tripleo.2011.06.038

      Objective

      High-dose-rate (HDR) brachytherapy using a customized mold is a minimally invasive treatment for oral cancer; however, it is difficult to use this technique for buccal and lip cancers involving the commissura labiorum, owing to its anatomic form. The purpose of this study was to introduce an improved customized mold consisting of 2 pieces to allow the fixation of molds to these sites.

      Study design

      Five patients with buccal carcinoma and 1 patient with lip carcinoma were treated with this technique after external beam radiotherapy. One patient with neck metastasis underwent both neck dissection and partial tumor resection before HDR brachytherapy.

      Results

      At the end of the follow-up period, 5 patients had no tumor recurrence, and 1 patient had suffered local recurrence.

      Conclusions

      Our technique is a viable therapeutic option for patients with buccal and lip carcinomas for whom the therapeutic modalities are limited by age, performance status, and other factors.
      Early-stage cancers of the buccal mucosa and lip are generally curable and can be treated with surgery or radiotherapy alone.
      • Sieczka E.
      • Datta R.
      • Singh A.
      • Loree T.
      • Rigual N.
      • Orner J.
      • et al.
      Cancer of the buccal mucosa: are margins and T-stage accurate predictors of local control?.
      • Pandey M.
      • Shukla M.
      • Nithya C.S.
      Pattern of lymphatic spread from carcinoma of the buccal mucosa and its implication for less than radical surgery.
      • Iyer S.G.
      • Pradhan S.A.
      • Pai P.S.
      • Patil S.
      Surgical treatment outcomes of localized squamous carcinoma of buccal mucosa.
      • Strome S.E.
      • To W.
      • Strawderman M.
      • Gersten K.
      • Devaney K.O.
      • Bradford C.R.
      • et al.
      Squamous cell carcinoma of the buccal mucosa.
      • Salgarelli A.C.
      • Sartorelli F.
      • Cangiano A.
      • Pagani R.
      • Collini M.
      Surgical treatment of lip cancer: our experience with 106 cases.
      • Vukadinovic M.
      • Jezdic Z.
      • Petrovic M.
      • Medenica L.M.
      • Lens M.
      Surgical management of squamous cell carcinoma of the lip: analysis of a 10-year experience in 223 patients.
      • Bucur A.
      • Stefanescu L.
      Management of patients with squamous cell carcinoma of the lower lip and N0-neck.
      • de Visscher J.G.
      • Gooris P.J.
      • Vermey A.
      • Roodenburg J.L.
      Surgical margins for resection of squamous cell carcinoma of the lower lip.
      • de Visscher J.G.
      • Botke G.
      • Schakenraad J.A.
      • van der Waal I.
      A comparison of results after radiotherapy and surgery for stage I squamous cell carcinoma of the lower lip.
      • de Visscher J.G.
      • van den Elsaker K.
      • Grond A.J.
      • van der Wal J.E.
      • van der Waal I.
      Surgical treatment of squamous cell carcinoma of the lower lip: evaluation of long-term results and prognostic factors—a retrospective analysis of 184 patients.
      • Antoniades D.Z.
      • Styanidis K.
      • Papanayotou P.
      • Trigonidis G.
      Squamous cell carcinoma of the lips in a northern Greek population Evaluation of prognostic factors on 5-year survival rate.
      • Mazeron J.J.
      • Ardiet J.M.
      • Haie-Méder C.
      • Kovács G.
      • Levendag P.
      • Peiffert D.
      • et al.
      GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas.
      • Mazeron J.J.
      • Noël G.
      • Simon J.M.
      Head and neck brachytherapy.
      • Pernot M.
      • Hoffstetter S.
      • Peiffert D.
      • Aletti P.
      • Lapeyre M.
      • Marchal C.
      • et al.
      Role of interstitial brachytherapy in oral and oropharyngeal carcinoma: reflection of a series of 1344 patients treated at the time of initial presentation.
      • Shibuya H.
      • Takeda M.
      • Matsumoto S.
      • Hoshina M.
      • Shagdarsuren M.
      • Suzuki S.
      Brachytherapy for nonmetastatic squamous cell carcinoma of the buccal mucosa An analysis of forty-five cases treated with permanent implants.
      • Horiuchi J.
      • Takeda M.
      • Shibuya H.
      • Matsumoto S.
      • Hoshina M.
      • Suzuki S.
      Usefulness of 198Au grain implants in the treatment of oral and oropharyngeal cancer.
      • Nair M.K.
      • Sankaranarayanan R.
      • Padmanabhan T.K.
      Evaluation of the role of radiotherapy in the management of carcinoma of the buccal mucosa.
      • Lock M.
      • Cao J.Q.
      • d'Souza D.P.
      • Hammond J.A.
      • Karnas S.
      • Lewis C.
      • et al.
      Brachytherapy with permanent gold grain seeds for squamous cell carcinoma of the lip.
      • Guibert M.
      • David I.
      • Vergez S.
      • Rives M.
      • Filleron T.
      • Bonnet J.
      • et al.
      Brachytherapy in lip carcinoma: long-term results.
      • Rovirosa-Casino A.
      • Planas-Toledano I.
      • Ferre-Jorge J.
      • Oliva-Díez J.M.
      • Conill-Llobet C.
      • Arenas-Prat M.
      Brachytherapy in lip cancer.
      • Gooris P.J.
      • Maat B.
      • Vermey A.
      • Roukema J.A.
      • Roodenburg J.L.
      Radiotherapy for cancer of the lip A long-term evaluation of 85 treated cases.
      • Farrús B.
      • Pons F.
      • Sánchez-Reyes A.
      • Ferrer F.
      • Rovirosa A.
      • Biete A.
      Quality assurance of interstitial brachytherapy technique in lip cancer: comparison of actual performance with the Paris System recommendations.
      • de Visscher J.G.
      • Grond A.J.
      • Botke G.
      • van der Waal I.
      Results of radiotherapy for squamous cell carcinoma of the vermilion border of the lower lip A retrospective analysis of 108 patients.
      For these cancers, radiotherapy, including brachytherapy, might be preferred owing to its favorable cosmetic and functional results. With external-beam radiation therapy (EBRT) alone, it is difficult to spare the adjacent normal tissues, such as the salivary glands and the jawbones, so these areas can sustain undesirable late effects. The advantages of brachytherapy are that it delivers a highly localized dose with rapid fall-off and that it requires only a short overall treatment duration.
      Brachytherapy is an effective treatment for cancers of the buccal mucosa and lip, and Ir-192 or Au-198 is usually used for low-dose-rate (LDR) interstitial irradiation.
      • Mazeron J.J.
      • Ardiet J.M.
      • Haie-Méder C.
      • Kovács G.
      • Levendag P.
      • Peiffert D.
      • et al.
      GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas.
      • Mazeron J.J.
      • Noël G.
      • Simon J.M.
      Head and neck brachytherapy.
      • Pernot M.
      • Hoffstetter S.
      • Peiffert D.
      • Aletti P.
      • Lapeyre M.
      • Marchal C.
      • et al.
      Role of interstitial brachytherapy in oral and oropharyngeal carcinoma: reflection of a series of 1344 patients treated at the time of initial presentation.
      • Shibuya H.
      • Takeda M.
      • Matsumoto S.
      • Hoshina M.
      • Shagdarsuren M.
      • Suzuki S.
      Brachytherapy for nonmetastatic squamous cell carcinoma of the buccal mucosa An analysis of forty-five cases treated with permanent implants.
      • Horiuchi J.
      • Takeda M.
      • Shibuya H.
      • Matsumoto S.
      • Hoshina M.
      • Suzuki S.
      Usefulness of 198Au grain implants in the treatment of oral and oropharyngeal cancer.
      • Nair M.K.
      • Sankaranarayanan R.
      • Padmanabhan T.K.
      Evaluation of the role of radiotherapy in the management of carcinoma of the buccal mucosa.
      • Lock M.
      • Cao J.Q.
      • d'Souza D.P.
      • Hammond J.A.
      • Karnas S.
      • Lewis C.
      • et al.
      Brachytherapy with permanent gold grain seeds for squamous cell carcinoma of the lip.
      • Guibert M.
      • David I.
      • Vergez S.
      • Rives M.
      • Filleron T.
      • Bonnet J.
      • et al.
      Brachytherapy in lip carcinoma: long-term results.
      • Rovirosa-Casino A.
      • Planas-Toledano I.
      • Ferre-Jorge J.
      • Oliva-Díez J.M.
      • Conill-Llobet C.
      • Arenas-Prat M.
      Brachytherapy in lip cancer.
      LDR brachytherapy causes some problems, however: It exposes medical staff to radiation, and it is necessary to isolate the patient. On the other hand, remote-afterloading high-dose-rate (HDR) brachytherapy using an Ir-192 microsource solves these problems.
      HDR brachytherapy for oral cancer is mainly performed using interstitial irradiation and has outcomes equivalent to LDR brachytherapy.
      • Finestres-Zubeldia F.
      • Guix-Melcior B.
      • Cloquell-Damian A.
      • Chimenos-Küstner E.
      • Tello-Luque J.I.
      Treatment of the carcinoma of the lip through high dose rate brachitherapy.
      • Petera J.
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      • Jirousek Z.
      • Tucek L.
      • Bedrosová J.
      • Frgala T.
      High dose rate brachytherapy in the treatment of oral cancer—the preliminary one institution experience.
      • Guinot J.L.
      • Arribas L.
      • Chust M.L.
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      • Carrascosa M.
      • et al.
      Lip cancer treatment with high dose rate brachytherapy.
      • Kakimoto N.
      • Inoue T.
      • Murakami S.
      • Furukawa S.
      • Yoshida K.
      • Yoshioka Y.
      • et al.
      Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer.
      • Leung T.W.
      • Wong V.Y.
      • Kwan K.H.
      • Ng T.Y.
      • Wong C.M.
      • Tung S.Y.
      • et al.
      High dose rate brachytherapy for early stage oral tongue cancer.
      • Nag S.
      • Cano E.R.
      • Demanes D.J.
      • Puthawala A.A.
      • Vikram B.
      American Brachytherapy Society
      The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for head-and-neck carcinoma.
      • Umeda M.
      • Komatsubara H.
      • Nishimatsu N.
      • Yokoo S.
      • Shibuya Y.
      • Komori T.
      High-dose rate interstitial brachytherapy for stage I-II tongue cancer.
      • Lau H.Y.
      • Hay J.H.
      • Flores A.D.
      • Threlfall W.J.
      Seven fractions of twice daily high dose-rate brachytherapy for node-negative carcinoma of the mobile tongue results in loss of therapeutic ratio.
      • Leung T.W.
      • Wong V.Y.
      • Wong C.M.
      • Tung S.Y.
      • Tsang A.
      • Lowes M.
      • et al.
      Technical hints for high dose rate interstitial tongue brachytherapy.
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      • Yamazaki H.
      • Koizumi M.
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      • Yoshida K.
      • Shiomi H.
      • et al.
      High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth.
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      • Wong V.Y.
      • Wong C.M.
      • Tung S.Y.
      • Lui C.M.
      • Leung L.C.
      • et al.
      High dose rate brachytherapy for carcinoma of the oral tongue.
      • Inoue T.
      • Teshima T.
      • Murayama S.
      • Shimizutani K.
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      • Furukawa S.
      • et al.
      Phase III trial of high and low dose rate interstitial radiotherapy for early oral tongue cancer.
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      • Schwarz R.
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      • Plambeck K.
      • et al.
      Interstitial high-dose rate brachytherapy with iridium-192 in patients with oral squamous cell carcinoma.
      Among the different types of HDR brachytherapy, intracavitary irradiation is a less invasive treatment than interstitial irradiation and is commonly used for the treatment of cancer of the uterine cervix.
      • Arai T.
      • Nakano T.
      • Morita S.
      • Sakashita K.
      • Nakamura Y.K.
      • Fukuhisa K.
      High-dose-rate remote afterloading intracavitary radiation therapy for cancer of the uterine cervix A 20-year experience.
      • Shigematsu Y.
      • Nishiyama K.
      • Masaki N.
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      • Miyata Y.
      • Ikeda H.
      • et al.
      Treatment of carcinoma of the uterine cervix by remotely controlled afterloading intracavitary radiotherapy with high-dose rate: a comparative study with a low-dose rate system.
      Some reports have described oral cancer treatments that use intracavitary irradiation with a customized mold and dental techniques, which can be performed as an outpatient treatment.
      • Kudoh T.
      • Ikushima H.
      • Kudoh K.
      • Tokuyama R.
      • Osaki K.
      • Furutani S.
      • et al.
      High-dose-rate brachytherapy for patients with maxillary gingival carcinoma using a novel customized intraoral mold technique.
      • Garrán C.
      • Montesdeoca N.
      • Martínez-Monge R.
      Treatment of upper gum carcinoma with high-dose-rate customized-mold brachytherapy.
      • Obinata K.
      • Ohmori K.
      • Shirato H.
      • Nakamura M.
      Experience of high-dose-rate brachytherapy for head and neck cancer treated by a customized intraoral mold technique.
      • Cengiz M.
      • Ozyar E.
      • Ersu B.
      • Akyol F.H.
      • Atahan I.L.
      High-dose-rate mold brachytherapy of early gingival carcinoma: a clinical report.
      • Ariji E.
      • Hayashi N.
      • Kimura Y.
      • Uchida T.
      • Hayashi K.
      • Nakamura T.
      Customized mold brachytherapy for oral carcinomas through use of high-dose-rate remote afterloading apparatus.
      These techniques are, however, limited to the treatment of superficial oral cancers, because the oral cavity is a wide space and there is no off-the-shelf applicator similar to the tandem and ovoid applicators that are available for the treatment of cancer of the uterine cervix. Superficial oral cancers are treated using a customized mold composed of a single plane, because the connection catheters are not sufficiently flexible to fit into the tumor. If these catheters could be arranged in 3 dimensions, this would expand the indications for the treatment of oral cancers. We therefore developed 2-piece molds, composed of intraoral and extraoral sections, and placed catheters into each section.
      We performed HDR brachytherapy using this 2-piece customized mold technique for oral cancers of the buccal mucosa and lip. The aim of the present article was to introduce our method and to evaluate its feasibility for the treatment of oral cancer.

      Materials and Methods

      Patients

      Between May 2007 and May 2010, 6 patients with cancer of the buccal mucosa or lip were treated using an HDR remote afterloading unit, an Ir-192 microsource (Micro-Selectron-HDR; Nucletron Co.), and a 2-piece customized mold at the Department of Radiology, Okayama University Hospital. The characteristics of the patients and their treatments are shown in Table I. All cases were histopathologically demonstrated to be squamous cell carcinoma. Our study obtained approval in accord with the Institutional Review Board standards of the individual institutions involved.
      Table IPatients and treatment characteristics
      Case no.Primary siteTNMAge (y)GenderPSTumor typeNo. of days between EBRT and HDRNo. of catheters usedNo. of treatment daysDose rate (cGy/min)Source strength (GBq)Follow-up period (mo)
      1BMT3N0M065F1Exophytic95 (2)37590-592321-32239
      2BMT1N0M076M1Superficial83 (1)37534-572290-31140
      3LLT2N0M088M1Exophytic74 (2)40412-441224-24036
      4BMT2N0M074M0Superficial84 (1)36412-441224-24027
      5BMT1N0M089M2Ulcerative85 (2)36298-643162-34921
      6BMT3N1M088F1Exophytic207 (2)48387-414210-2253
      Numbers in parentheses are numbers of catheters at extraoral side.
      PS, performance status; EBRT, external beam radiation therapy; HDR, high-dose-rate; BM, buccal mucosa; LL, lower lip.
      One patient's tumor (case 1) was inoperable, because neoadjuvant chemotherapy caused respiratory failure (Fig. 1, A and B). Four patients (cases 2-5) had not been treated previously and had either refused surgical treatment or were difficult to treat surgically because of their ages or poor performance statuses (Figs. 1, C and D [lower lip], and 2, A and B [buccal mucosa]). One patient (case 6) with submandibular lymph node metastasis was selected for HDR brachytherapy at the primary site, based on her age, functional results, and wishes. For the lymph node metastasis, she underwent supraomohyoid neck dissection 3 weeks before the start of radiotherapy.
      Figure thumbnail gr1
      Fig. 1Photographs taken before and after treatment in cases 1 and 3. A, B, Case 1: buccal carcinoma (A) before treatment and (B) 3 months after treatment. C, D, Case 3: lower lip carcinoma (C) before treatment and (D) 5 months after treatment.

      Treatment protocol

      We planned a treatment protocol in which EBRT was performed before HDR brachytherapy for all patients to reduce the thickness of the tumor and to determine the treatment area. EBRT involving a total dose of 30 Gy (2 Gy/d; 5 fractions/wk) was performed with a 4-MV x-ray using opposing pair fields. To make the mold, an impression of the tumor including the surrounding tissue was made for each patient. This was done using silicone impression material before or during the EBRT. HDR brachytherapy was performed 1 week after the completion of the EBRT. Two 6-Gy fractions were delivered twice a day for 2 days a week with an interval of >6 hours between the fractions. The total HDR brachytherapy dose was 24 Gy.
      In the patient who underwent supraomohyoid neck dissection (case 6), sufficient tumor shrinkage had not occurred at the end of the EBRT; therefore, part of the tumor was resected to decrease its thickness before the HDR brachytherapy was started. To allow wound recovery after the resection, the HDR brachytherapy was started 2 weeks after the completion of the EBRT.

      Mold production and HDR brachytherapy planning

      We used a silicone impression material to take the impressions used to make the molds (Exafine; GC Corp., Shanghai, China). In the buccal-carcinoma cases, we took impressions around the tumors, including the adjacent teeth, buccal alveolar sulci, commissura labiorum, and the skin of the cheeks. For edentulous patients, we took the impressions while they were wearing their complete lower jaw dentures. For a lip carcinoma, we included the lower incisors, oral vestibule, lower lip, and mentolabial sulcus. For both types of cases, we took the impression while pushing and spreading out the mucosa surrounding the tumor to decrease its thickness. The teeth were included in the impression to provide stability to decrease movement during irradiation. The molds were made of acrylic resin (Ortho Crystal; Nissin Dental Products, Japan) on plaster (New Plastone IILE; GC Corp., Japan) models and were divided into intraoral and extraoral sections (Fig. 2, C-F).
      Figure thumbnail gr2
      Fig. 2Photographs of and treatment process used in case 5 (buccal carcinoma). A, B, Before treatment. C, D, Plaster model; the red area is the clinical target volume. E, F, Two-piece customized mold; Left piece, extraoral side; right piece, intraoral side. G, Seven days after treatment. H, Three months after treatment.
      To embed the catheters into the molds, the gross tumor volume (GTV) was evaluated by radiation oncologists and dental radiologists after the EBRT, because the tumor margin was often different after the irradiation. We determined the area displaying mucositis after the EBRT as the GTV, and 5 mm was added to the GTV to give the clinical target volume (CTV). The catheters were embedded in parallel ∼10 mm apart so that they could cover a sufficient proportion of the CTV. Catheters were embedded into both the intraoral and the extraoral sections. Each dose reference point was set at 7 mm from the catheter center in all cases, after considering the distance from the mucosal and/or skin surface to the embedded catheter.
      The dose distributions were calculated using a special computer system (Plato Brachytherapy, Nucletron Co., The Netherlands; Fig. 3) . We used silicone impression materials to fix the molds in place during the HDR brachytherapy irradiation (Fig. 4) . Except for the patient who underwent partial tumor resection (case 6), we performed HDR radiotherapy 1 week after the completion of the EBRT.
      Figure thumbnail gr3
      Fig. 3Dose distributions of case 5. A, 3D View. B, Y-Z plane. C, Z-X plane.
      Figure thumbnail gr4
      Fig. 4Schema for the fixation of the customized mold to the adjacent teeth. CM, Customized mold; CT, catheter tubes; SIM, silicone impression material.

      Results

      The total treatment period ranged from 36 to 48 days. Treatment was not suspended owing to radiation complications or other reasons in any patient. The source strength for each fraction ranged from 161.7 to 349.2 GBq. The total treatment time, including the time required for preparation, was no longer than 15 minutes for any fraction, and the actual irradiation time ranged from 108 to 234 seconds. All patients suffered from grade 2 dermatitis and mucositis but recovered within 4 months of treatment. The follow-up period ranged from 3 to 40 months.
      One patient with lip carcinoma (case 3) developed regional metastasis 5 months after treatment and was salvaged with radical neck dissection. One patient (case 4) developed local recurrence outside the CTV margin which was controlled with additional HDR brachytherapy (24 Gy/4 fractions/2 weeks) 8 months after the initial treatment. One patient (case 5) suffered local failure and received additional HDR brachytherapy (24 Gy/4 fractions/2 weeks) 4 months after the initial treatment. Although his tumor showed further growth, he was salvaged with surgery 6 months after the initial treatment (Fig. 2, G and H). One patient (case 6) died of pneumonia 3 months after treatment. At the end of the follow-up period, 5 patients (excluding case 6) were disease free.

      Discussion

      Because the lip and buccal mucosa are visible sites, cancers in these tissues are often discovered at an early stage and are curable by surgery or radiotherapy alone.
      • Sieczka E.
      • Datta R.
      • Singh A.
      • Loree T.
      • Rigual N.
      • Orner J.
      • et al.
      Cancer of the buccal mucosa: are margins and T-stage accurate predictors of local control?.
      • Pandey M.
      • Shukla M.
      • Nithya C.S.
      Pattern of lymphatic spread from carcinoma of the buccal mucosa and its implication for less than radical surgery.
      • Iyer S.G.
      • Pradhan S.A.
      • Pai P.S.
      • Patil S.
      Surgical treatment outcomes of localized squamous carcinoma of buccal mucosa.
      • Strome S.E.
      • To W.
      • Strawderman M.
      • Gersten K.
      • Devaney K.O.
      • Bradford C.R.
      • et al.
      Squamous cell carcinoma of the buccal mucosa.
      • Salgarelli A.C.
      • Sartorelli F.
      • Cangiano A.
      • Pagani R.
      • Collini M.
      Surgical treatment of lip cancer: our experience with 106 cases.
      • Vukadinovic M.
      • Jezdic Z.
      • Petrovic M.
      • Medenica L.M.
      • Lens M.
      Surgical management of squamous cell carcinoma of the lip: analysis of a 10-year experience in 223 patients.
      • Bucur A.
      • Stefanescu L.
      Management of patients with squamous cell carcinoma of the lower lip and N0-neck.
      • de Visscher J.G.
      • Gooris P.J.
      • Vermey A.
      • Roodenburg J.L.
      Surgical margins for resection of squamous cell carcinoma of the lower lip.
      • de Visscher J.G.
      • Botke G.
      • Schakenraad J.A.
      • van der Waal I.
      A comparison of results after radiotherapy and surgery for stage I squamous cell carcinoma of the lower lip.
      • de Visscher J.G.
      • van den Elsaker K.
      • Grond A.J.
      • van der Wal J.E.
      • van der Waal I.
      Surgical treatment of squamous cell carcinoma of the lower lip: evaluation of long-term results and prognostic factors—a retrospective analysis of 184 patients.
      • Antoniades D.Z.
      • Styanidis K.
      • Papanayotou P.
      • Trigonidis G.
      Squamous cell carcinoma of the lips in a northern Greek population Evaluation of prognostic factors on 5-year survival rate.
      • Mazeron J.J.
      • Ardiet J.M.
      • Haie-Méder C.
      • Kovács G.
      • Levendag P.
      • Peiffert D.
      • et al.
      GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas.
      • Mazeron J.J.
      • Noël G.
      • Simon J.M.
      Head and neck brachytherapy.
      • Pernot M.
      • Hoffstetter S.
      • Peiffert D.
      • Aletti P.
      • Lapeyre M.
      • Marchal C.
      • et al.
      Role of interstitial brachytherapy in oral and oropharyngeal carcinoma: reflection of a series of 1344 patients treated at the time of initial presentation.
      • Shibuya H.
      • Takeda M.
      • Matsumoto S.
      • Hoshina M.
      • Shagdarsuren M.
      • Suzuki S.
      Brachytherapy for nonmetastatic squamous cell carcinoma of the buccal mucosa An analysis of forty-five cases treated with permanent implants.
      • Horiuchi J.
      • Takeda M.
      • Shibuya H.
      • Matsumoto S.
      • Hoshina M.
      • Suzuki S.
      Usefulness of 198Au grain implants in the treatment of oral and oropharyngeal cancer.
      • Nair M.K.
      • Sankaranarayanan R.
      • Padmanabhan T.K.
      Evaluation of the role of radiotherapy in the management of carcinoma of the buccal mucosa.
      • Lock M.
      • Cao J.Q.
      • d'Souza D.P.
      • Hammond J.A.
      • Karnas S.
      • Lewis C.
      • et al.
      Brachytherapy with permanent gold grain seeds for squamous cell carcinoma of the lip.
      • Guibert M.
      • David I.
      • Vergez S.
      • Rives M.
      • Filleron T.
      • Bonnet J.
      • et al.
      Brachytherapy in lip carcinoma: long-term results.
      • Rovirosa-Casino A.
      • Planas-Toledano I.
      • Ferre-Jorge J.
      • Oliva-Díez J.M.
      • Conill-Llobet C.
      • Arenas-Prat M.
      Brachytherapy in lip cancer.
      • Gooris P.J.
      • Maat B.
      • Vermey A.
      • Roukema J.A.
      • Roodenburg J.L.
      Radiotherapy for cancer of the lip A long-term evaluation of 85 treated cases.
      • Farrús B.
      • Pons F.
      • Sánchez-Reyes A.
      • Ferrer F.
      • Rovirosa A.
      • Biete A.
      Quality assurance of interstitial brachytherapy technique in lip cancer: comparison of actual performance with the Paris System recommendations.
      • de Visscher J.G.
      • Grond A.J.
      • Botke G.
      • van der Waal I.
      Results of radiotherapy for squamous cell carcinoma of the vermilion border of the lower lip A retrospective analysis of 108 patients.
      LDR and HDR brachytherapy, which deliver highly localized doses with rapid fall-off and require only short overall treatment durations, are effective treatments for these cancers owing to their favorable cosmetic and functional results.
      • Mazeron J.J.
      • Ardiet J.M.
      • Haie-Méder C.
      • Kovács G.
      • Levendag P.
      • Peiffert D.
      • et al.
      GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas.
      • Mazeron J.J.
      • Noël G.
      • Simon J.M.
      Head and neck brachytherapy.
      • Pernot M.
      • Hoffstetter S.
      • Peiffert D.
      • Aletti P.
      • Lapeyre M.
      • Marchal C.
      • et al.
      Role of interstitial brachytherapy in oral and oropharyngeal carcinoma: reflection of a series of 1344 patients treated at the time of initial presentation.
      • Shibuya H.
      • Takeda M.
      • Matsumoto S.
      • Hoshina M.
      • Shagdarsuren M.
      • Suzuki S.
      Brachytherapy for nonmetastatic squamous cell carcinoma of the buccal mucosa An analysis of forty-five cases treated with permanent implants.
      • Horiuchi J.
      • Takeda M.
      • Shibuya H.
      • Matsumoto S.
      • Hoshina M.
      • Suzuki S.
      Usefulness of 198Au grain implants in the treatment of oral and oropharyngeal cancer.
      • Nair M.K.
      • Sankaranarayanan R.
      • Padmanabhan T.K.
      Evaluation of the role of radiotherapy in the management of carcinoma of the buccal mucosa.
      • Lock M.
      • Cao J.Q.
      • d'Souza D.P.
      • Hammond J.A.
      • Karnas S.
      • Lewis C.
      • et al.
      Brachytherapy with permanent gold grain seeds for squamous cell carcinoma of the lip.
      • Guibert M.
      • David I.
      • Vergez S.
      • Rives M.
      • Filleron T.
      • Bonnet J.
      • et al.
      Brachytherapy in lip carcinoma: long-term results.
      • Rovirosa-Casino A.
      • Planas-Toledano I.
      • Ferre-Jorge J.
      • Oliva-Díez J.M.
      • Conill-Llobet C.
      • Arenas-Prat M.
      Brachytherapy in lip cancer.
      • Finestres-Zubeldia F.
      • Guix-Melcior B.
      • Cloquell-Damian A.
      • Chimenos-Küstner E.
      • Tello-Luque J.I.
      Treatment of the carcinoma of the lip through high dose rate brachitherapy.
      • Petera J.
      • Dolezel M.
      • Jirousek Z.
      • Tucek L.
      • Bedrosová J.
      • Frgala T.
      High dose rate brachytherapy in the treatment of oral cancer—the preliminary one institution experience.
      • Guinot J.L.
      • Arribas L.
      • Chust M.L.
      • Mengual J.L.
      • Garcia-Miragall E.
      • Carrascosa M.
      • et al.
      Lip cancer treatment with high dose rate brachytherapy.
      • Kakimoto N.
      • Inoue T.
      • Murakami S.
      • Furukawa S.
      • Yoshida K.
      • Yoshioka Y.
      • et al.
      Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer.
      • Leung T.W.
      • Wong V.Y.
      • Kwan K.H.
      • Ng T.Y.
      • Wong C.M.
      • Tung S.Y.
      • et al.
      High dose rate brachytherapy for early stage oral tongue cancer.
      • Nag S.
      • Cano E.R.
      • Demanes D.J.
      • Puthawala A.A.
      • Vikram B.
      American Brachytherapy Society
      The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for head-and-neck carcinoma.
      • Umeda M.
      • Komatsubara H.
      • Nishimatsu N.
      • Yokoo S.
      • Shibuya Y.
      • Komori T.
      High-dose rate interstitial brachytherapy for stage I-II tongue cancer.
      • Lau H.Y.
      • Hay J.H.
      • Flores A.D.
      • Threlfall W.J.
      Seven fractions of twice daily high dose-rate brachytherapy for node-negative carcinoma of the mobile tongue results in loss of therapeutic ratio.
      • Leung T.W.
      • Wong V.Y.
      • Wong C.M.
      • Tung S.Y.
      • Tsang A.
      • Lowes M.
      • et al.
      Technical hints for high dose rate interstitial tongue brachytherapy.
      • Inoue T.
      • Yamazaki H.
      • Koizumi M.
      • Kagawa K.
      • Yoshida K.
      • Shiomi H.
      • et al.
      High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth.
      • Leung T.W.
      • Wong V.Y.
      • Wong C.M.
      • Tung S.Y.
      • Lui C.M.
      • Leung L.C.
      • et al.
      High dose rate brachytherapy for carcinoma of the oral tongue.
      • Inoue T.
      • Teshima T.
      • Murayama S.
      • Shimizutani K.
      • Fuchihata H.
      • Furukawa S.
      • et al.
      Phase III trial of high and low dose rate interstitial radiotherapy for early oral tongue cancer.
      • Friedrich R.E.
      • Krüll A.
      • Hellner D.
      • Schwarz R.
      • Heyer D.
      • Plambeck K.
      • et al.
      Interstitial high-dose rate brachytherapy with iridium-192 in patients with oral squamous cell carcinoma.
      • Prisciandaro J.I.
      • Foote R.L.
      • Herman M.G.
      • Lee S.J.
      • LaJoie W.N.
      • van Blarcom A.B.
      • et al.
      A buccal mucosa carcinoma treated with high dose rate brachytherapy.
      In addition, these treatments are less invasive than surgery and are often selected as alternatives to LDR and HDR interstitial irradiation, which are relatively invasive treatments. It is difficult to use interstitial irradiation for the treatment of elderly patients, patients with poor performance statuses, and those with declining physical conditions. HDR brachytherapy using a customized mold technique is a minimally invasive treatment and is able to solve these problems.
      • Kudoh T.
      • Ikushima H.
      • Kudoh K.
      • Tokuyama R.
      • Osaki K.
      • Furutani S.
      • et al.
      High-dose-rate brachytherapy for patients with maxillary gingival carcinoma using a novel customized intraoral mold technique.
      • Garrán C.
      • Montesdeoca N.
      • Martínez-Monge R.
      Treatment of upper gum carcinoma with high-dose-rate customized-mold brachytherapy.
      • Obinata K.
      • Ohmori K.
      • Shirato H.
      • Nakamura M.
      Experience of high-dose-rate brachytherapy for head and neck cancer treated by a customized intraoral mold technique.
      • Cengiz M.
      • Ozyar E.
      • Ersu B.
      • Akyol F.H.
      • Atahan I.L.
      High-dose-rate mold brachytherapy of early gingival carcinoma: a clinical report.
      • Ariji E.
      • Hayashi N.
      • Kimura Y.
      • Uchida T.
      • Hayashi K.
      • Nakamura T.
      Customized mold brachytherapy for oral carcinomas through use of high-dose-rate remote afterloading apparatus.
      This technique does, however, involve some problems associated with the cancer subsite and the form of the original mold, and these need to be overcome.
      With cancers of the tongue, it can be difficult to fix the molds in place, and therefore methods such as traditional LDR brachytherapy and interstitial HDR brachytherapy are commonly used. During the treatment of cancers of the gingiva or palate, care must be taken to prevent osteoradionecrosis caused by the exposure of the contiguous jawbone to radiation, although molds have the advantage of being able to be fastened to the teeth. Most of the commonly used molds are composed of a single plane, owing to the use of rigid catheters, and are suitable only for the treatment of superficial tumors. Our molds consist of multiple planes and make it possible to treat cancers of the buccal mucosa around the buccoalveolar sulcus but are unsuitable for cancers that extend into the commissura labiorum. Similarly, the lips form curved surfaces; therefore, we modified the original molds by separating them into 2 pieces, intraoral and extraoral sections, and embedded catheters into each section along different axes, thereby making it possible to sandwich the tumor between them.
      Using this improved customized mold, we considered that an appropriate dose distribution could be obtained for the first patient, who had a buccal carcinoma expanding into the commissura labiorum. This patient was affected by respiratory failure during the neoadjuvant chemotherapy and required the use of biphasic positive airway pressure. We planned HDR brachytherapy using an improved customized mold, owing to the difficulty of surgery and/or isolating the patient. The patient achieved a complete response; therefore, we used this technique for 5 other patients, 4 of whom also achieved a complete response, including 1 with lymph node metastasis. The 1 patient who achieved a partial response received additional HDR brachytherapy and as a result was salvaged by surgery because of tumor recurrence.
      Regarding the dose, fractionation schedule, and whether to combine HDR brachytherapy with EBRT, several authors have reported various schemes for HDR brachytherapy using customized mold techniques for the treatment of oral cancer (Table II).
      • Kudoh T.
      • Ikushima H.
      • Kudoh K.
      • Tokuyama R.
      • Osaki K.
      • Furutani S.
      • et al.
      High-dose-rate brachytherapy for patients with maxillary gingival carcinoma using a novel customized intraoral mold technique.
      • Garrán C.
      • Montesdeoca N.
      • Martínez-Monge R.
      Treatment of upper gum carcinoma with high-dose-rate customized-mold brachytherapy.
      • Obinata K.
      • Ohmori K.
      • Shirato H.
      • Nakamura M.
      Experience of high-dose-rate brachytherapy for head and neck cancer treated by a customized intraoral mold technique.
      • Cengiz M.
      • Ozyar E.
      • Ersu B.
      • Akyol F.H.
      • Atahan I.L.
      High-dose-rate mold brachytherapy of early gingival carcinoma: a clinical report.
      • Ariji E.
      • Hayashi N.
      • Kimura Y.
      • Uchida T.
      • Hayashi K.
      • Nakamura T.
      Customized mold brachytherapy for oral carcinomas through use of high-dose-rate remote afterloading apparatus.
      Twenty-eight cases of lip carcinoma were treated with HDR brachytherapy using external polymethyl methacrylate molds and were administered 60-65 Gy in 33-36 fractions (tumors >4 cm were administered total doses ranging from 75 to 80 Gy) without EBRT.
      • Finestres-Zubeldia F.
      • Guix-Melcior B.
      • Cloquell-Damian A.
      • Chimenos-Küstner E.
      • Tello-Luque J.I.
      Treatment of the carcinoma of the lip through high dose rate brachitherapy.
      In that series, only 2 cases displayed local recurrence, and 1 patient suffered local failure. In the present study, 1 patient developed local recurrence. We consider that the low dose administered to the tumor was the reason for the above-mentioned failure. The reported total biologically effective dose (BED) for HDR brachytherapy combined with EBRT ranged from 65.4 to 147 Gy according to the linear quadrant model using an α/β ratio of 10, and only 2 cases received doses that were lower than that used in our regimen (74.4 Gy). Furthermore, in our cases, which occurred far from the jawbone, there was less concern about exposing the jawbone to irradiation than in the earlier reported cases, and dermatitis and mucositis of up to grade 2 were observed as acute complications. Because our technique mainly uses surface applicators, the deeper parts of the tumor did not receive sufficient doses, and because of this, we might change our HDR brachytherapy scheme from 24 Gy in 4 fractions to 30 Gy in 5 fractions or 36 Gy in 6 fractions (total BED 84 or 93.6 Gy).
      Table IIHDR brachytherapy using customized mold technique for oral cavity cancers
      Author (year)RefAge (y)GenderLocationEBRTHDR brachytherapy
      Cengiz (1999)4270FUG40 Gy/10 fr/5 d
      86FUG40 Gy/10 fr/5 d
      Ariji (1999)4364MFM22 Gy/11 fr30 Gy/10 fr/5 d
      64MBM26 Gy/13 fr35 Gy/10 fr/5 d
      59MFM30 Gy/15 fr30 Gy/10 fr/5 d
      48MLG40 Gy/20 fr25 Gy/10 fr/5 d
      Obinata (2007)4173MLG60 Gy/24 fr24 Gy/4 fr/2 d
      76MUG30 Gy/12 fr30 Gy/5 fr/3 d
      Garran (2008)4064FUG46 Gy/23 fr (IMRT)32 Gy/8 fr/4 d
      Kudoh (2010)3980FUG60 Gy/30 fr50 Gy/10 fr/5 d
      79FUG60 Gy/30 fr30 Gy/10 fr/5 d
      Ref, reference; EBRT, external beam radiation therapy; HDR, high-dose-rate; UG, upper gingiva; FM, floor of mouth; BM, buccal mucosa; LG, lower gingiva; fr, fraction; IMRT, intensity-modulated radiation therapy.
      Some authors have reported on the administration of HDR brachytherapy using a customized mold technique without EBRT for lip and oral cancers, and they showed high control rates.
      • Finestres-Zubeldia F.
      • Guix-Melcior B.
      • Cloquell-Damian A.
      • Chimenos-Küstner E.
      • Tello-Luque J.I.
      Treatment of the carcinoma of the lip through high dose rate brachitherapy.
      • Cengiz M.
      • Ozyar E.
      • Ersu B.
      • Akyol F.H.
      • Atahan I.L.
      High-dose-rate mold brachytherapy of early gingival carcinoma: a clinical report.
      There have also been some studies that reported good outcomes for interstitial HDR brachytherapy without EBRT for carcinomas of the lip, tongue, and the floor of mouth.
      • Petera J.
      • Dolezel M.
      • Jirousek Z.
      • Tucek L.
      • Bedrosová J.
      • Frgala T.
      High dose rate brachytherapy in the treatment of oral cancer—the preliminary one institution experience.
      • Guinot J.L.
      • Arribas L.
      • Chust M.L.
      • Mengual J.L.
      • Garcia-Miragall E.
      • Carrascosa M.
      • et al.
      Lip cancer treatment with high dose rate brachytherapy.
      • Kakimoto N.
      • Inoue T.
      • Murakami S.
      • Furukawa S.
      • Yoshida K.
      • Yoshioka Y.
      • et al.
      Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer.
      • Leung T.W.
      • Wong V.Y.
      • Kwan K.H.
      • Ng T.Y.
      • Wong C.M.
      • Tung S.Y.
      • et al.
      High dose rate brachytherapy for early stage oral tongue cancer.
      • Nag S.
      • Cano E.R.
      • Demanes D.J.
      • Puthawala A.A.
      • Vikram B.
      American Brachytherapy Society
      The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for head-and-neck carcinoma.
      • Umeda M.
      • Komatsubara H.
      • Nishimatsu N.
      • Yokoo S.
      • Shibuya Y.
      • Komori T.
      High-dose rate interstitial brachytherapy for stage I-II tongue cancer.
      • Inoue T.
      • Yamazaki H.
      • Koizumi M.
      • Kagawa K.
      • Yoshida K.
      • Shiomi H.
      • et al.
      High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth.
      • Leung T.W.
      • Wong V.Y.
      • Wong C.M.
      • Tung S.Y.
      • Lui C.M.
      • Leung L.C.
      • et al.
      High dose rate brachytherapy for carcinoma of the oral tongue.
      • Inoue T.
      • Teshima T.
      • Murayama S.
      • Shimizutani K.
      • Fuchihata H.
      • Furukawa S.
      • et al.
      Phase III trial of high and low dose rate interstitial radiotherapy for early oral tongue cancer.
      • Friedrich R.E.
      • Krüll A.
      • Hellner D.
      • Schwarz R.
      • Heyer D.
      • Plambeck K.
      • et al.
      Interstitial high-dose rate brachytherapy with iridium-192 in patients with oral squamous cell carcinoma.
      The BEDs described in those reports (67.5-96 Gy) were less than or equal to those for our cases, excluding the regimen of 60 Gy in 10 fractions. Regarding the concentration of the dose on the tumor, HDR brachytherapy alone might be superior to HDR brachytherapy combined with EBRT. We performed EBRT to reduce the tumor thickness, and the GTV was determined according to the area that displayed mucositis after irradiation. We set the administration dose with EBRT to 30 Gy after considering the dose that could be tolerated (TD100 [%] = 32 Gy) by salivary glands, especially parotid glands, included in the irradiation field. Otherwise, our treatment period was <8 weeks, as recommended by the American Brachytherapy Society. Increasing the HDR brachytherapy dose and decreasing the EBRT dose might be better for shortening the treatment period while administering a sufficient tumor dose.
      Eight months after treatment, 1 patient with buccal carcinoma suffered recurrence in the CTV margin. We had defined the CTV as the GTV + 5 mm to reduce the area subject to complications. In addition, we improved our customized mold by extending the area covered by the resin to include the mandibular teeth to avoid set-up error, and fixed the mold in place with silicone impression material. We consider that the CTV might need to be greater than GTV + 5 mm to prevent marginal recurrence.
      For the patient whose tumor was not decreased by EBRT, we performed tumor resection to reduce the tumor thickness before the start of the HDR brachytherapy. This patient suffered metastasis to a submandibular lymph node. Radical neck dissection is reported to be the most successful treatment for neck lymph node metastasis;
      • Leipzig B.
      • Hokanson J.A.
      Treatment of cervical lymph nodes in carcinoma of the tongue.
      therefore, after considering the potential functional results and patient age, we performed surgery for the neck metastasis and radiotherapy for the primary tumor. The patient achieved a complete response and wound surface repair at 1.5 months. Unfortunately, the patient died of pneumonia 3 months after treatment. We consider that combined therapy (such as tumor resection with HDR brachytherapy and neck dissection with HDR brachytherapy for the primary site) is useful for elderly patients, owing to its potentially improved functional results.
      In this report, we have introduced HDR brachytherapy using an improved customized-mold technique for buccal and lip carcinoma. One patient achieved a partial response and another suffered local recurrence; therefore, it might be possible to improve the total dose of EBRT and/or HDR brachytherapy with or without EBRT and to adjust the CTV margin. We consider our technique, however, to be an appropriate treatment option for patients with buccal and lip carcinomas for whom therapeutic modalities are limited by age, performance status, and other reasons. These patients might have further therapeutic options, such as irradiation after tumor reduction by surgery and/or treating the primary tumor with brachytherapy combined with neck dissection.

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