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Long-term outcome research on PDR brachytherapy with focus on breast, base of tongue and lip cancer
Örebro University, School of Health and Medical Sciences. (onkologi, medicinsk strålfysik, brachyterapi)
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Brachytherapy (BT) with continuous low dose rate (LDR) has been used for 100 years and is considered as the radiotherapy method able to deliver a dose in the shortest time with high efficacy and low risk of side effects. The drawbacks are need for patient isolation and radiation exposure of the staff during the treatment.

Brenner and Hall published the radiobiology concept for pulsed dose rate (PDR) in 1991.  Short (10-20 minutes), hourly pulses of high dose rate (HDR) given to the same dose, with same overall treatment time will virtually simulate continuous LDR. At the same time new afterloading machine technology became available, where a single millimetre sized radiation 192Iridium source sequentially moves through the applicator in small individually timed steps. The advantages are that the radiation dose can be optimized along the applicator and with no radiation exposure of the staff and no need for patient isolation more than during the pulse. This work deals with four different aspects of PDR BT

An experimental comparison of measured absorbed doses outside a left sided breast target on a body equivalent Alderson phantom was made.  Five external beam radiotherapy (EBRT) whole breast treatments to 50 Gy versus five accelerated partial breast irradiations (APBI) by PDR BT to 50 Gy were studied. The absorbed doses were measured in 67 different positions inside the body phantom by thermoluminescence dosimeters. The result shows that dose points distant to the left breast will have 1-1.4 % of the prescribed dose with no difference between EBRT and PDR BT. Organs at risk in short distance (<5 cm) to the target (such as parts of the left lung, heart muscle and the right breast) will have significantly less dose by PDR BT. In conclusion PDR BT has dosimetric advantages close to the target compared to EBRT and cannot do more damage to remote organs.

PDR APBI as the adjuvant RT treatment to breast conserving surgery after early breast cancer was studied. Between 1994-2004 we treated 50 women and 51 breasts. The median age of the population was 53 (40-72) years. The cases were radically resected, unifocal T1-2N0-1M0 tumours. PDR BT was given to a dose of 50 Gy for 5 days directed to the operated sector of the breast. The median treated volume was 160 cm3, constituting in median 31 % of the breast volume. The treatment is called accelerated because total treatment time is 5 days compared to 5 weeks for EBRT. After a median follow-up of 130 months (>10 years) we noted 5 (10 %) local recurrences in the treated breast. Four of these recurrences were outside the treated volume. Three women (6 %) developed cancers in the other breast. Early side effects were mild and less than with EBRT. As late side effects we found mild to moderate local fibroses in the treated volume. A cosmetic evaluation was done by both the patient and a nurse and was found to be lower than in other published data (56 % = good to excellent). The 10 years local failure rate is similar to the result from a large Swedish randomized study on whole breast radiotherapy to 50 Gy. The study indicates that PDR BT is highly effective.

A combination of EBRT (40.8 Gy) and PDR boost (35 Gy) to T1-4N0-3M0, base of tongue (BOT) cancer, treated during 1994-2007 was analyzed. The study is the first with PDR and second largest with BT worldwide. A number of 83 patients with a median age of 60 (38-82) years were included. BT was given to a mean volume of 58 ccm 2 days after the neck dissection. Median follow-up was 54 months. At 5 years we found 89 % local tumour control, 95 % neck control, 80 % disease free survival and an overall survival of 65 %. Late side effects were 13 % minor transient soft tissue necrosis and 12 % long lasting or permanent soft tissue- or osteoradio-necrosis. The results are among the best published worldwide. An extensive quality of life analysis was done on 45 patients at last follow-up and showed limited, persistent xerostomia and dysphagia. The global quality of life was rated good in 75 % of the patients.

The last study presented was PDR mono-brachytherapy (55-60 Gy) to cancer of the lip (T1-3N0M0). The study included 43 patients with a median age of 74 (37-92) years. The treatment time was 5.5-6 days and the mean treated volume was 15 ccm. The median follow-up time was 54 (1-158) months. Five year Kaplan-Meier data showed, local control 94 %, disease free survival 86 % and overall survival 59 %. An early side effect was a strong radiation mucositis and dermatitis, which healed in 1 month. Late side effects were uncommon and the cosmetic appearance and the lip function were found to be normal. Our data in total and per T-stage was compared to a European survey from 1993 on 2794 patients treated by LDR BT. The results are similar and are a strong indication of equal efficacy between PDR and LDR.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2010. , 81 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 42
Keyword [en]
PDR, brachytherapy, outcome, partial breast irradiation, base of tongue cancer, lip cancer, quality of life, dosimetry.
National Category
Cancer and Oncology Surgery
Research subject
Oncology; Surgery
Identifiers
URN: urn:nbn:se:oru:diva-10423ISBN: 978-91-7668-723-9 (print)OAI: oai:DiVA.org:oru-10423DiVA: diva2:311246
Public defence
2010-05-21, Wilandersalen, M-huset, bottenvåning, Universitetssjukhuset, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2011-04-26Bibliographically approved
List of papers
1. Phantom study of radiation doses outside the target volume brachytherapy versus external radiotherapy of early breast cancer
Open this publication in new window or tab >>Phantom study of radiation doses outside the target volume brachytherapy versus external radiotherapy of early breast cancer
2003 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 69, no 1, 107-112 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: Brachytherapy is sometimes suggested as an adjuvant treatment after surgery of some tumours. When introducing this, it would be useful to have an estimate of the dose distribution to different body sites, both near and distant to target, comparing conventional external irradiation to brachytherapy. The aim of the present study was to determine radiation doses with both methods at different body sites, near and distant to target, in an experimental situation on an operated left sided breast cancer on a female Alderson phantom. METHODS: Five external beam treatments with isocentric tangential fields were given by a linear accelerator. A specified dose of 1.0 Gy was given to the whole left sided breast volume. Five interstitial brachytherapy treatments were given to the upper, lateral quadrant of the left breast by a two plane, 10 needles implant. A dose of 1.0 Gy specified according to the Paris system was administered by a pulsed dose rate afterloading machine. Absorbed dose in different fixed dose points were measured by thermoluminescence dosimeters. RESULTS: Both methods yielded an absorbed dose of the same size to the bone marrow and internal organs distant to target, 1.0-1.4% of the prescribed dose. There was a trend of lower doses to the lower half of the trunk and higher doses to the upper half of the trunk, respectively, by brachytherapy. A 90% reduction of absorbed dose with brachytherapy compared to external irradiation was found in the near-target region within 5 cm from target boundary where parts of the left lung and the heart are situated. If an adjuvant dose of 50 Gy is given with the external radiotherapy and brachytherapy, the absorbed dose in a part of the myocardium could be reduced from 31.8 to 2.1 Gy. CONCLUSIONS: Near target, brachytherapy yielded a considerably lower absorbed dose which is of special importance when considering radiation effects on the myocard and lungs. We could not demonstrate any difference of importance, in absorbed dose to dose points distant to target.

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2003
Keyword
Brachytherapy; PDR; External radiotherapy; Breast cancer; Radiation dose distribution; TL dosimetry
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-10402 (URN)10.1016/S0167-8140(03)00241-X (DOI)14597363 (PubMedID)
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2016-12-07Bibliographically approved
2. Pulsed dose rate brachytherapy as the sole adjuvant radiotherapy after breast-conserving surgery of T1-T2 breast cancer: first long time results from a clinical study
Open this publication in new window or tab >>Pulsed dose rate brachytherapy as the sole adjuvant radiotherapy after breast-conserving surgery of T1-T2 breast cancer: first long time results from a clinical study
Show others...
2009 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 90, no 1, 30-35 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: To evaluate the long time outcome with regard to local tumour control, cosmetic outcome and side effects of a short (5 days) accelerated interstitial brachytherapy treatment delivered to the surroundings of the operated sector. PATIENTS AND METHODS: Between 1993 and 2003 we treated 50 women with early T1 and T2 breast cancer. Radical sector resection was performed and followed later with an interstitial pulsed dose rate (PDR) brachytherapy of 50Gy in 5 days. The treatment was centred on the tumour with a margin of 30mm. One patient was treated bilaterally. The patients were followed for a median of 86 (32-126) months. RESULTS: Ipsilateral breast cancer recurrence was seen in 3 patients (6%). Two of them occurred outside the treated volume. The 5- and 7-year rates of actuarial local control were 96% and 96%, respectively, overall survival 88% and 85%, disease free survival 88% and 88%, respectively. A dosimetrical analysis showed that the partial breast irradiation covered a median of 31% of the total breast volume. Fat necrosis was seen in 12% and local (moderate-strong) fibrosis in 26% of the patients. Independent cosmetic scoring showed good or excellent result in 56% of the patients. CONCLUSIONS: Local outcome is favourable and very similar to other published studies of accelerated partial breast irradiation. Our long time cosmetic results are lower than other published results.

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2009
Keyword
Brachytherapy; Pulsed dose rate; Breast cancer; Accelerated partial breast irradiation; Cosmetics; Outcome; Radiotherapy
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-10401 (URN)10.1016/j.radonc.2008.02.022 (DOI)000262958000004 ()18410975 (PubMedID)2-s2.0-58149235035 (Scopus ID)
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2017-03-15Bibliographically approved
3. Long term results from a uniform clinical series on pulsed dose rate brachytherapy as the boost to external beam irradiation in base of tongue cancer
Open this publication in new window or tab >>Long term results from a uniform clinical series on pulsed dose rate brachytherapy as the boost to external beam irradiation in base of tongue cancer
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background and purpose: To evaluate the long time outcome with regard to local tumour control, side effects and quality of life of a combined pulsed dose rate (PDR) boost and hyperfractionated accelerated external beam radiotherapy (EBRT) for primary base of tongue (BOT) cancers.

Patients and methods: Between 1994 and 2007 we treated 83 patients, median age 60 (38-82) years, with primary T1-T4 BOT cancers. Seven patients (8 %) were T1-2N0 (AJCC stage I-II) and 76 (92 %) patients were T1-2N+ or T3-4N0-3 (AJCC stage III-IV). The mean estimated primary tumour volume was 15 (1-75) cm3.  EBRT was given with 1.7 Gy twice daily to 40,8 Gy to primary tumour and bilateral neck lymph nodes in 2.5 weeks. A PDR boost of 35 Gy and a neck dissection in clinical node positive cases was performed 2-3 weeks later. The patients were followed for a median of 54 (2-168) months.

Results: The 2-, 5- and 10-years rates of actuarial local control were 91 %, 89 % and 85 %, overall survival 85 %, 65 % and 44 %, disease free survival 86 %, 80 % and 76 % respectively. The regional contral rate was 95 %. Six patients (7 %) developed distant metastases. Analysis of dosimetry showed a mean treated volume of 58 cm3.  In a review of late complications we found 11 (13 %) minor and 4 (5 %) major soft tissue necroses and 6 (7 %) osteoradionecroses. The patients median subjective SOMA/LENT scoring at last follow up was; grade 0 for pain and trismus, grade 1 for dysphagia and taste alteration and grade 2 for xerostomia. Global visual-analog-scale (VAS) scoring of quality of life was 8.

Conclusions: Local and regional tumour control rate was excellent in this treatment protocol. The data support that PDR boost is at least as effective as published continuous low dose rate (CLDR) results.

Keyword
Brachytherapy; Pulsed dose rate; Base of Tongue cancer; Outcome; Radio-therapy
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-10406 (URN)
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2016-12-12Bibliographically approved
4. Pulsed dose rate monobrachytherapy for cancer of the lip: first long time results from a clinical study
Open this publication in new window or tab >>Pulsed dose rate monobrachytherapy for cancer of the lip: first long time results from a clinical study
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background and purpose: To evaluate the long time outcome with regard to local tumour control and side effects of a pulsed dose rate (PDR) monobrachytherapy of primary or recurrent cancr of the lip.

Patients and methods: Between 1995 and 2007 we treated 43 patients with primary or recurrent T1-T3 lip cancers. The clinical stage was T1N0 for 22 patients (51 %), T2N0 for 16 patients (37 %) and T3N0 for 5 patients (12 %). A median dose of 60 (55-66) Gy was given, depending on the tumour volume. The PDR treatment was given with 0.83 Gy/pulse every second hour for 5.5-6.5 days. The patients were followed for a median of 55 (1-158) months.

Results: The 2-, 5- and 10-years rates of actuarial local control were 97.6 %, 94.5 % and 94.5 %, overall survival 88.0 %, 58.9 % and 39.1 %, disease free survival 92.7 %, 86.4 % and 86.4 % respectively. The regional control rate was 93 %. One patient (2 %) developed distant metastases. A dosimetrical analysis showed a mean treated volume of 14.9 (3.0-56.2) cm3.  In a review of late complications we found 1 (2 %) soft tissue necrosis and 1 (2 %) osteoradionecrosis. Long-term side effects were very mild and the cosmetic outcome excellent.

Conclusions: Local outcome is excellent and very similar to other published studies of continuous low dose rate (cLDR) brachytherapy.

Keyword
Brachytherapy; Pulsed dose rate; Lip cancer; Outcome; Radiotherapy
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-10417 (URN)
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2016-12-08Bibliographically approved

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