- Email: [email protected]
24 Phase III trial of HDR versus LDR interstitial brachytherapy as monotherapy for early carcinoma of the mobile tongue
20 ENDOBRONCHIAL BRACHYTHERAPY OF LUNG CANCER H.-N. Macha, Hemer, Germany In the management of advanced lung cancer palliative endobronchial brachytherapy has been established as an effective and safe treatment procedure. In symptoms such as hemoptysis, poststenotic pneumonia, cough and breathlessness by endobronchial obstruction clinical success rates up to 90% have been achieved. Endobronchial brachytherapy has become the backbone in interventional bronchoscopy as it can be combined successfully with other palliative procedures e.g. endobronchial laseresection, cryocoagulation or endobronchial stent implantation. Far more interesting is a new trend in endobronchial brachytherapy which aims at a curative approach in strictly limited lung cancer growth in the central airways. With the development of devices using the autofluorescence or enhanced fluorescence properties of tumour cells by Argon Laser light the detection of early lung cancer in the central airway system is now feasible. Such tumours being not visible by normal light endoscopy are strictly limited to the bronchia wall, offering ideal conditions for curative endobronchial radiation therapy. Long term survival has been reported by endobronchial brachytherapy solely. Only one treatment technique which has the same target is competing with brachytherapy, endobronchial photodynamic therapy. Combining both therapeutic techniques results in high rates of complete remission and a 90% three years survival. Thus endobronchial brachytherapy is a valuable tool in a curative multidisciplinary approach in the treatment of lung cancer. 21 BRACHYTHERAPY FOR LUNG CANCER Burton L. Speiser, M.D., M.S., F.A.C.R. Learning Objective To be knowledgeable in the use of brachytherapy for lung cancer and its effective use.
Abstract The session will cover the use of brachytherapy for lung cancer. Covered will be the use of Interstitial 1-125 and Endobronchial Brachytherapy. Included will be the treatment of Occult Carcinoma. Special emphasis will be placed on the speaker's results in four studies combining more than 680 patients. Analysis will be presented to illustrate endobronchial radiation ability to treat endoluminal disease. Both a literature review and indepth analysis of fatal hemoptyses will be presented.
22 BRACHYTHERAPY IN ORAL CAVITY CANCER Jean-Jacques MAZERON. Centre des Tumeurs, Groupe Hospitalier Piti6-Salp6tri6re, 47-83 Boulevard de l'H6pital, 75651 Paris cedex 13, France. Limited stage squamous cell carcinoma of the oral cavity can be treated with surgery and/or external beam irradiation and/or implantation of iridium 192 sources. The major advantage of brachytherapy over external beam radiation therapy is a high-localised dose with a rapid fall-off, and a short overall treatment duration. The primary tumour volume receives a total dose, which could not be safely delivered by external beam radiotherapy alone, and the rapid fall-off allows relative sparing of critical normal tissues, such as the mandible, salivary glands, and mastication muscles. A large experience has been accumulated with low dose rate (LDR) brachytherapy in the treatment of squamous cell carcinoma of oral cavity, 4 cm or less in diameter. Recent analysis of large clinical series provided data indicating that modalities of LDR brachytherapy of these tumours should be optimised for increasing therapeutic ratio. It is now recommended that the primary tumour should be exclusively treated by iridium 192, with a total dose of 65-70 Gy, a dose rate of 0.3-0.6 Gy/hr, an intersource spacing of 1-1.4 cm, and the systematic use of a custom made lead gutter shielding the mandible during irradiation. LDR brachytherapy is now challenged by high dose rate (HDR) brachytherapy and pulsed dose rate (PDR) brachytherapy. Preliminary results obtained with these last two modalities will be discussed in comparison with those of LDR brachytherapy. Results obtained with definitive HDR brachytherapy of T1-2 squamous cell carcinomas of mobile tongue are conflicting. PDR brachytherapy is an interesting modality from a technical and radiobiological point of view. For No patients, the neck could be electively treated with neck dissection or closely followed, with neck dissection reserved for nodal relapse. If a postoperative external beam irradiation of the neck is to delivered, the implanted area is protected by a cerrobend block. At the moment, despite a randomised trial comparing the two attitudes and showing similar results, there is no consensus on this point. 24 PHASE Ill TRIAL OF HDR VERSUS LDR INTERSTITIALBRACHYTHERAPYAS MONOTHERAPYFOR EARLY CARCINOMAOF THE MOBILETONGUE Toshihiko Inoue, Takehiro Inoue, Ken Yoshida, Yasuo Yoshioka, Shigetoshi Shgimamoto and Hideya Yamazaki Division of Multidisciplinary Radiotherapy, Biomedical Research Centre, Osaka University Graduate School of Medicine (D10), Suita, Japan Purpose: to investigate the possibility whether HDR hyperfractionated interstitial brachytherapy is an alternative to LDR continuous one as monotherapy for early mobile tongue cancer based on the long follow-up. Methods and materials: In April 1992, we started our phase 111 study of interstitial brachytherapy as monotherapy for mobile tongue cancer based on our phase l/II study of HDR hyperfractionated interstitial brachytherapy for oral cancer. We selected patients with T1-T2NOM0 lesions on the
19
lateral border, treated with single plane implantation and with tumor thickness being 10 nun or less. Patients with a performance status from 0 to 2 entered this study and informed consent was obtained. In the LDR group patients received 70 Gy over 4 to 9 days. In the HDR group patients received 60 Gy in 10 fractions over 6 days. From April 1992 to October 1996, we classified 29 patients into a LDR group, and 30 patients into a HDR group. Three patients from the LDR and 5 patients from the HDR groups were later removed from the study due to refusals of personal reason, double-plane implantation and nonstandard fractionation. Therefore, 26 patients in LDR and 25 patients in HDR were eligible for assessment. There were no significant differences of T-category, age and gender between the groups. Results: Five-year cause specific survival rates of the LDR and HDR groups were 85% and 88%, respectively. Five-year local recurrence-free survival rates were 90% and 92%, respectively. Local tumor recurrences developed in 4 patients in the LDR group and in 2 patients in the HDR. Nodal metastases occurred in 6 patients in each of the groups. Nine of these 12 patients were salvaged by neck dissections. Two patients in the LDR group and one in the HDR died from primary tumors. One patient died from nodal metastases in the LDR group and similarly two in the HDR group. One in each of the groups developed soft tissue ulcers. Two patients in the HDR group developed bone exposure of the mandible, one of them being treated without a spacer. Conclusions: Treatment results and adverse effects of HDR hyperfractionated interstitial brachytherapy as monotherapy for mobile tongue cancer were the same as, or superior to, that of LDR continuous interstitial brachytherapy. 25 PROGNOSTIC FACTORS OF CONSERVATIVE TREATMENT W I T H EXTERNAL BEAM IRRADIATION AND LDR IRIDIUM 192 BRACHYTHERAPY FOR VELOTONSILLAR CARCINOMA L A R G E R THAN 4 CENTIMETERS 1 2 3 I 1 PEIFFERT D , MECELLEM H , BARONMH, HOFFSTE'I'IERS , LAPEYREM 1. Centre Alexis Vautrin, avenue de Bourgogne, F-54511 Vandoeuvre-les-Nancy cedex, France 2. Centre Francois Baclesse - L - 4005 Esch-sur-Alzette, Luxembourg 3. Centre Hospitalier Jean Minjoz, F - 25030 Besan9on Cedex, France
Introduction. Velotonsillar squamous cell carcinoma larger than 4 cm (T3, T4) are often treated by surgery and postoperative external beam irradiation (EBI). We analyzed the results of a series of patients (pts) treated by EBI and brachytherapy (BT). Methods and materials : From 1977 to 1993, 104 pts were treated by EBI and BT in a curative intent: 96 men, 8 women, mean age 56 years (39 to 79). The mean size of the tumor was 4.5 cm in length (2 to 8), 2.5 cm width (0.8 to 5) and 1.5 cm thickness (0.3 to 4.5) and the tumoral mean volume reached 18.75 cc (2.8 to 11) (L x 1 x t). The primary tumor site was the soft palate for 26 pts, the tonsil for 70 pts and the glossotonsillar sulcus in 8 pts. Fifty-six pts had neck node invasion. The treatment began with EBI 50 Gy in 25 fractions over 5 weeks. An additional treatment in case of involved lymph nodes was delivered by electrontherapy or surgical sampling. A boost by interstitial BT with Iridium 192 wires using a loop technique [Pernot et al Int J Radiat Oncol Biol Phys 23: 715-723, 1992], (mean of 3 loops) delivered 30 Gy (16.1 to 36) at a LDR of 0.49 Gy/h on the reference isodose (min 0.23, max 1,07) to a mean volume of 61 cc (7.3 to 178). The mean follow up ofpts alive is 8 years (1 to 20 years). Results: Local control was achieved for 78 pts; node failures occurred in 4 pts, local failures occurred in 18 pts, and locoregional in 8 pts. Of the 26 local failures, only 2 were successfully salvaged by surgery. Eighty-four pts died, and 39 from their primitive cancer. Actuarial 5-year overall and specific survivals were 40% and 57% respectively. Late complications occurred in 38 patients with mucosal ulceration combined in 5 pts with osteoradionecrosis. Forty pts present neither local recurrence and nor complication (38.5%). Statistical analysis reveals a significant relationship between local control and interval between EBI and BT (20 vs. 28d.:p=0.02), the total duration of the whole treatment (61 vs. 70d: p=0.01), the width of the tumor (2.5 vs. 3.1 cm:p=0.006) and the tumor volume (20 vs 27cc : p=0.04). The initial tumor site (soft palate vs. tonsil), the thickness of the tumor, the BT treated volume, the number of the iridium wires, the EBI total dose, the BT dose, and the node invasion were not significant for local control. Conclusion: Conservative treatment of velotonsillar cancer greater than 4 cm (T3-T4) with EBI and interstitial BT achieves a high local control rate and a good functional result for 38.5% of the pts. For this selected group with large tumors, the delay between the 2 sessions of irradiation, the total irradiation duration and the tumoral volume (through width) were found prognostic factors for local control. 26 INTERSTITIALLDR IR 192 BRACHYTHERAPYIN STAGE T2 PRIMARIES OF THE MOBILE TONGUE Peiffert D, Hoffstetter S, Lapeyre M Department of Radiation Oncology, Centre Alexis Vautrin, 54511 Vandoeuvre-l~s-Nancy Cedex, France Objective: to evaluate the tumor control and the late complications in patients (pts) treated by exclusive irradiation using the loop technique of brachytherapy (BT) for T2 carcinomas of the tongue. Patients and methods: From 1979 to 1994, 154 pts (120 M, 34 F, mean age: 58 years) presenting a first primary (squamous cell carcinoma) of the mobile tongue were curatively treated by exclusive BT or combined external beam irradiation (EBI) and BT. Patients treated by local resection or treated for local relapse, or presenting a second primary were excluded, as well as pts treated by hair-pins. The median tumor size was 3.2 cm (range 2.3 to 4) and the infiltration was 1.4 cm (range 0.3 to 3.5), some of them being probably stages T4. The median tumor volume was 6.3 cc (range 0.9 to 36). One hundred pts had no clinical node involvement. All the pts were implanted with plastic tubes using the loop technique and manually afterloaded with lr 192 wires. Three to 6 loops were implanted. A lead protection of the mandible was weared during the treatment. The mean dose rate was 0.7 Gy/h on the 85% reference dose of the Paris system. A group of 81 pts (74 T2N0, 7T2N1) was treated by exclusive BT on the primary (mean dose: 66 Gy) and a neck node dissection. In case of involved nodes, a neck irradiation was delivered. A group of 73 pts (44 T2 N0, 29 T2 N1-3) was treated by local and neck EBI (median dose: 43.5 Gy), a BT boost of the primary (34.5 Gy) and a limited neck dissection. The median follow-up of the patients alive was 9 years (range 2 to 20).
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Abstract The session will cover the use of brachytherapy for lung cancer. Covered will be the use of Interstitial 1-125 and Endobronchial Brachytherapy. Included will be the treatment of Occult Carcinoma. Special emphasis will be placed on the speaker's results in four studies combining more than 680 patients. Analysis will be presented to illustrate endobronchial radiation ability to treat endoluminal disease. Both a literature review and indepth analysis of fatal hemoptyses will be presented.
22 BRACHYTHERAPY IN ORAL CAVITY CANCER Jean-Jacques MAZERON. Centre des Tumeurs, Groupe Hospitalier Piti6-Salp6tri6re, 47-83 Boulevard de l'H6pital, 75651 Paris cedex 13, France. Limited stage squamous cell carcinoma of the oral cavity can be treated with surgery and/or external beam irradiation and/or implantation of iridium 192 sources. The major advantage of brachytherapy over external beam radiation therapy is a high-localised dose with a rapid fall-off, and a short overall treatment duration. The primary tumour volume receives a total dose, which could not be safely delivered by external beam radiotherapy alone, and the rapid fall-off allows relative sparing of critical normal tissues, such as the mandible, salivary glands, and mastication muscles. A large experience has been accumulated with low dose rate (LDR) brachytherapy in the treatment of squamous cell carcinoma of oral cavity, 4 cm or less in diameter. Recent analysis of large clinical series provided data indicating that modalities of LDR brachytherapy of these tumours should be optimised for increasing therapeutic ratio. It is now recommended that the primary tumour should be exclusively treated by iridium 192, with a total dose of 65-70 Gy, a dose rate of 0.3-0.6 Gy/hr, an intersource spacing of 1-1.4 cm, and the systematic use of a custom made lead gutter shielding the mandible during irradiation. LDR brachytherapy is now challenged by high dose rate (HDR) brachytherapy and pulsed dose rate (PDR) brachytherapy. Preliminary results obtained with these last two modalities will be discussed in comparison with those of LDR brachytherapy. Results obtained with definitive HDR brachytherapy of T1-2 squamous cell carcinomas of mobile tongue are conflicting. PDR brachytherapy is an interesting modality from a technical and radiobiological point of view. For No patients, the neck could be electively treated with neck dissection or closely followed, with neck dissection reserved for nodal relapse. If a postoperative external beam irradiation of the neck is to delivered, the implanted area is protected by a cerrobend block. At the moment, despite a randomised trial comparing the two attitudes and showing similar results, there is no consensus on this point. 24 PHASE Ill TRIAL OF HDR VERSUS LDR INTERSTITIALBRACHYTHERAPYAS MONOTHERAPYFOR EARLY CARCINOMAOF THE MOBILETONGUE Toshihiko Inoue, Takehiro Inoue, Ken Yoshida, Yasuo Yoshioka, Shigetoshi Shgimamoto and Hideya Yamazaki Division of Multidisciplinary Radiotherapy, Biomedical Research Centre, Osaka University Graduate School of Medicine (D10), Suita, Japan Purpose: to investigate the possibility whether HDR hyperfractionated interstitial brachytherapy is an alternative to LDR continuous one as monotherapy for early mobile tongue cancer based on the long follow-up. Methods and materials: In April 1992, we started our phase 111 study of interstitial brachytherapy as monotherapy for mobile tongue cancer based on our phase l/II study of HDR hyperfractionated interstitial brachytherapy for oral cancer. We selected patients with T1-T2NOM0 lesions on the
19
lateral border, treated with single plane implantation and with tumor thickness being 10 nun or less. Patients with a performance status from 0 to 2 entered this study and informed consent was obtained. In the LDR group patients received 70 Gy over 4 to 9 days. In the HDR group patients received 60 Gy in 10 fractions over 6 days. From April 1992 to October 1996, we classified 29 patients into a LDR group, and 30 patients into a HDR group. Three patients from the LDR and 5 patients from the HDR groups were later removed from the study due to refusals of personal reason, double-plane implantation and nonstandard fractionation. Therefore, 26 patients in LDR and 25 patients in HDR were eligible for assessment. There were no significant differences of T-category, age and gender between the groups. Results: Five-year cause specific survival rates of the LDR and HDR groups were 85% and 88%, respectively. Five-year local recurrence-free survival rates were 90% and 92%, respectively. Local tumor recurrences developed in 4 patients in the LDR group and in 2 patients in the HDR. Nodal metastases occurred in 6 patients in each of the groups. Nine of these 12 patients were salvaged by neck dissections. Two patients in the LDR group and one in the HDR died from primary tumors. One patient died from nodal metastases in the LDR group and similarly two in the HDR group. One in each of the groups developed soft tissue ulcers. Two patients in the HDR group developed bone exposure of the mandible, one of them being treated without a spacer. Conclusions: Treatment results and adverse effects of HDR hyperfractionated interstitial brachytherapy as monotherapy for mobile tongue cancer were the same as, or superior to, that of LDR continuous interstitial brachytherapy. 25 PROGNOSTIC FACTORS OF CONSERVATIVE TREATMENT W I T H EXTERNAL BEAM IRRADIATION AND LDR IRIDIUM 192 BRACHYTHERAPY FOR VELOTONSILLAR CARCINOMA L A R G E R THAN 4 CENTIMETERS 1 2 3 I 1 PEIFFERT D , MECELLEM H , BARONMH, HOFFSTE'I'IERS , LAPEYREM 1. Centre Alexis Vautrin, avenue de Bourgogne, F-54511 Vandoeuvre-les-Nancy cedex, France 2. Centre Francois Baclesse - L - 4005 Esch-sur-Alzette, Luxembourg 3. Centre Hospitalier Jean Minjoz, F - 25030 Besan9on Cedex, France
Introduction. Velotonsillar squamous cell carcinoma larger than 4 cm (T3, T4) are often treated by surgery and postoperative external beam irradiation (EBI). We analyzed the results of a series of patients (pts) treated by EBI and brachytherapy (BT). Methods and materials : From 1977 to 1993, 104 pts were treated by EBI and BT in a curative intent: 96 men, 8 women, mean age 56 years (39 to 79). The mean size of the tumor was 4.5 cm in length (2 to 8), 2.5 cm width (0.8 to 5) and 1.5 cm thickness (0.3 to 4.5) and the tumoral mean volume reached 18.75 cc (2.8 to 11) (L x 1 x t). The primary tumor site was the soft palate for 26 pts, the tonsil for 70 pts and the glossotonsillar sulcus in 8 pts. Fifty-six pts had neck node invasion. The treatment began with EBI 50 Gy in 25 fractions over 5 weeks. An additional treatment in case of involved lymph nodes was delivered by electrontherapy or surgical sampling. A boost by interstitial BT with Iridium 192 wires using a loop technique [Pernot et al Int J Radiat Oncol Biol Phys 23: 715-723, 1992], (mean of 3 loops) delivered 30 Gy (16.1 to 36) at a LDR of 0.49 Gy/h on the reference isodose (min 0.23, max 1,07) to a mean volume of 61 cc (7.3 to 178). The mean follow up ofpts alive is 8 years (1 to 20 years). Results: Local control was achieved for 78 pts; node failures occurred in 4 pts, local failures occurred in 18 pts, and locoregional in 8 pts. Of the 26 local failures, only 2 were successfully salvaged by surgery. Eighty-four pts died, and 39 from their primitive cancer. Actuarial 5-year overall and specific survivals were 40% and 57% respectively. Late complications occurred in 38 patients with mucosal ulceration combined in 5 pts with osteoradionecrosis. Forty pts present neither local recurrence and nor complication (38.5%). Statistical analysis reveals a significant relationship between local control and interval between EBI and BT (20 vs. 28d.:p=0.02), the total duration of the whole treatment (61 vs. 70d: p=0.01), the width of the tumor (2.5 vs. 3.1 cm:p=0.006) and the tumor volume (20 vs 27cc : p=0.04). The initial tumor site (soft palate vs. tonsil), the thickness of the tumor, the BT treated volume, the number of the iridium wires, the EBI total dose, the BT dose, and the node invasion were not significant for local control. Conclusion: Conservative treatment of velotonsillar cancer greater than 4 cm (T3-T4) with EBI and interstitial BT achieves a high local control rate and a good functional result for 38.5% of the pts. For this selected group with large tumors, the delay between the 2 sessions of irradiation, the total irradiation duration and the tumoral volume (through width) were found prognostic factors for local control. 26 INTERSTITIALLDR IR 192 BRACHYTHERAPYIN STAGE T2 PRIMARIES OF THE MOBILE TONGUE Peiffert D, Hoffstetter S, Lapeyre M Department of Radiation Oncology, Centre Alexis Vautrin, 54511 Vandoeuvre-l~s-Nancy Cedex, France Objective: to evaluate the tumor control and the late complications in patients (pts) treated by exclusive irradiation using the loop technique of brachytherapy (BT) for T2 carcinomas of the tongue. Patients and methods: From 1979 to 1994, 154 pts (120 M, 34 F, mean age: 58 years) presenting a first primary (squamous cell carcinoma) of the mobile tongue were curatively treated by exclusive BT or combined external beam irradiation (EBI) and BT. Patients treated by local resection or treated for local relapse, or presenting a second primary were excluded, as well as pts treated by hair-pins. The median tumor size was 3.2 cm (range 2.3 to 4) and the infiltration was 1.4 cm (range 0.3 to 3.5), some of them being probably stages T4. The median tumor volume was 6.3 cc (range 0.9 to 36). One hundred pts had no clinical node involvement. All the pts were implanted with plastic tubes using the loop technique and manually afterloaded with lr 192 wires. Three to 6 loops were implanted. A lead protection of the mandible was weared during the treatment. The mean dose rate was 0.7 Gy/h on the 85% reference dose of the Paris system. A group of 81 pts (74 T2N0, 7T2N1) was treated by exclusive BT on the primary (mean dose: 66 Gy) and a neck node dissection. In case of involved nodes, a neck irradiation was delivered. A group of 73 pts (44 T2 N0, 29 T2 N1-3) was treated by local and neck EBI (median dose: 43.5 Gy), a BT boost of the primary (34.5 Gy) and a limited neck dissection. The median follow-up of the patients alive was 9 years (range 2 to 20).
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