Brachy a Dying Art
Evolution of IMRT, SBRT—Is Brachytherapy a dying art in gynaecological malignancies?
Brachytherapy has been an uncontested form of radiotherapy in almost all forms of gynaecological malignancies. It has been used in almost all stages of cancers of the cervix, endometrial carcinomas, vulval and vaginal malignancies.
Brachytherapy has a long and successful history in the treatment of gynaecological cancers. The first successful applications of radioisotopes to treat cancer were reported shortly after the discovery of radium in 1898. Over the next century and more, the evolution of brachytherapy into a valued component of the radiotherapy for many malignancies became firmly established. For locally advanced cervical cancer, the standard treatment consists of a combination of external-beam radiation therapy (EBRT) along with concomitant chemotherapy followed by a brachytherapy boost . Brachytherapy has also been used in early-stage endometrial and cervical cancers as the sole curative treatment and as an adjuvant treatment in post-operative cases of cervical and endometrial carcinomas. As a boost, brachytherapy has been proved to increase local control and also to increase overall survival. The beauty of brachytherapy lies in its conformity and an unmatchable dose fall off; thus it allows for a high dose to the tumor while sparing the nearby normal structures. Brachytherapy delivers a highly effective dose to the primary tumor– more than 80-85 Gy biologically equivalent dose in 2-Gy fractions (EQD2) to the tumor periphery while the central part of the tumour receives even higher doses (>120 Gy EQD2). The ability to safely deliver a high dose to central disease explains the excellent local control rates that can be achieved when cervical cancers are treated with a combination of EBRT and brachytherapy. It would be impossible to deliver so high a tumoricidal dose using EBRT alone as it would lead to significant dose to nearby normal structures (mainly rectum, small bowel, and bladder), entailing a high probability of acute and late toxicity.
The physics behind this is simple. The radioactive source is placed very close to the target to be treated. Because of the inverse-square law (the radiation dose decreases exponentially with distance; so as distance goes from 𝑥 to 2𝑥, the radiation dose decreases from 𝑦 to 0.25𝑦), the nearby normal tissues receive a much lower dose, while the target tissues receives a very high dose
But inspite of the advantages, many patients may not be able to take this form of the treatment, because of several factors like, medical comorbidities, unfavourable anatomy, and others. Since SBRT ( Stereotactic Body Radiotherapy) too offers a high dose conformity allowing a high dose to the target and sparing normal structures around, there is a growing curiosity if SBRT could be used for this group of patients. Such patients have been treated in the past with EBRT as a boost in place of brachytherapy with overall very poor results. Barraclough et al have reported his experience on 44 patients treated with external-beam boost instead of brachytherapy (“technical limitations” was listed as the reason in 73% of patients) and found a 48% recurrence rate with a median follow up of 2.3 years. While this treatment may be better than no radiation boost at all, but a high local failure rate cannot be avoided.
Recently, Han et al published Surveillance, Epidemiology, and End Results (SEER) data for brachytherapy use in patients treated for cervical cancer in the United States. In this study of 7359 patients who received EBRT between 1988 and 2009, only 63% were also reported to have received brachytherapy. The rate of brachytherapy use also dropped from 75%-80% in the 1980s and 1990s to < 60% in 2003. Significantly, patients who were treated with combined EBRT and brachytherapy had a far better overall survival than those treated with EBRT alone (65% and 50%, respectively); there were no significant differences in non-cancer-related deaths between the 2 groups. This fall is inspite of the recent technological advances in image guided planning and delivery of brachytherapy for cervical cancer reporting impressive local control rates of 100% for stage IB, 96% for stage IIB, and 86% for stage IIIB patients.
The fall in brachytherapy could have been due to the rise of use of IMRT during that period. However, interpreting records from SEER should be done with caution. The data do suggest that there might have been a real decrease in the use of brachytherapy after the year 2000 due to inappropriate applications of EBRT, decreasing brachytherapy training and expertise, and failure of clinicians who lacked the ability or resources to administer brachytherapy to refer patients to centres with greater expertise.
Among all EBRT boost techniques mentioned above, SBRT simulates a brachytherapy dose distribution most closely, with sharp dose gradient. In SBRT, multiple noncoplanar beams intersect within the target volume. This produces a high-dose being delivered to the tumor, while maximally sparing the surrounding tissue. In fact, several dosimetric studies have favored SBRT for optimal target coverage and OAR sparing , In one study, SBRT boost plans were created for 11 cervical cancer patients and compared in dose distribution to Brachytherapy boost plans. Rectal dose to 1 cc (d1cc), bladder d1cc, and median target coverage by the 100% isodose line were all superior in the SBRT plans. In yet another study volumetric-modulated arc therapy (VMAT) dosimetric plans were generated for 51 gynecologic cancer patients, and similarly demonstrated that compared to BT, SBRT yielded favorable rectal d1cc, d2cc, and maximum dose, with comparable doses to bladder and bowel, although BT offered superior integral dose and PTV coverage . Although dosimetrically comparable, the outcome may not be the same.
Recently, Gill et al used the National Cancer Data Base to analyze the radiation dose-escalation technique that was used in the treatment of 7,654 patients with cervical cancer. From 2004 to 2011, use of brachytherapy decreased from 96.7% to 86.1% whereas use of IMRT and SBRT increased from 3.3% to 13.9% (P.01). The median survival time was 70.9 months for patients who received brachytherapy compared with 47.1 months for those dose-escalated with either IMRT or SBRT as an alternative to brachytherapy. The risk of cervical cancer-specific death was significantly higher for women who did not receive brachytherapy (hazard ratio of 1.86) despite controlling for several relevant clinical and pathologic factors. Of particular note, the increase in the mortality rate was more pronounced for patients who did not receive brachytherapy than for those who did not receive chemotherapy.
At RGCI, SBRT has been done in about 10 patients, who were not suitable for the invasive intra cavitary brachytherapy, with good and comparable local control. Our current treatment protocol is to treat to 20-25 Gy in four to five fractions using dose constraints as described previously.
SBRT Plan simulating HDR brachytherapy plan.
Conclusion
Most of the available data to date are retrospective and heterogeneous. But some trends do emerge from these studies. First of all, there appears to be good local control with SBRT or IMRT according to some studies. Secondly, the major late toxicity seen in the published studies are late GI toxicities.
It has also been seen that the survival is compromised when brachytherapy is omitted. Hence at present, it is not recommended that we replace brachytherapy with SBRT or IMRT in patients who are eligible candidates for brachytherapy. However, when a patient is not suitable for brachytherapy, SBRT can be a safe and effective treatment modality. Further work in this area can be used to better define SBRT dose and to prospectively collect toxicity and outcome information on this patient subset.
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