Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications.
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Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer. Brachytherapy is a specific form of radiation therapy used to treat cancer.
It consists of placing sealed, radioactive sources directly into or next to the tumor to be treated, either directly or by means of catheters. Brachytherapy has been a part of antineoplastic treatments since the development of contact brachytherapy in the early s. A few years after the discovery of radioactivity, Pierre Curie and Alexander Graham Bell independently observed shrinkage of malignant tumors when radioactive sources were implanted directly inside a mass.
In , brachytherapy remains an optimal tool in the context of radiation use for patients and may involve a wide range of medical specialties in either the referral to or the placement of brachytherapy.
Schematically, radiation therapy is indicated in 3 major situations: 1 as curative, definitive radiotherapy with or without chemotherapy ; 2 as adjuvant treatment to decrease the probability of local relapse after surgery; and 3 as palliative treatment of symptomatic metastases. The common objective of all irradiation techniques is to deliver a radiation dose to the tumor that is high enough to eradicate tumor cells without leading to unacceptable damage to normal tissues.
The therapeutic index of irradiation relies on the differential response between tumors and normal tissue, as tumors cells have a lower DNA repair capability compared with normal tissue cells. Therefore, the ideal technique should be able to deliver therapeutic doses to the tumor with doses as low as possible to the organs at risk.
Schematically, 2 possibilities do exist for delivering therapeutic irradiation: EBRT and brachytherapy. In EBRT techniques, which are the most commonly used, the irradiation comes from beams generated outside the patient. All of those techniques have been developed to increase the ratio between tumor dose and normal tissue dose. The fundamental specificity of brachytherapy is that it relies on the implantation of radioactive sources or catheters secondarily loaded with radioactive sources within the tumor interstitial brachytherapy or very close to the tumor plesiotherapy.
The implantation is guided by clinical findings and any relevant imaging modality.
In some situations, the precise perioperative placement of brachytherapy catheters may need expertise from organ specialists, including urologists, gynecologic surgeons, cardiologists, gastroenterologists, pneumologists, surgical oncologists, interventional radiologists, orthopedists, or dermatologists. This multidisciplinary approach is particularly required for perioperative procedures, in case the target volume is not easily accessible without endoscopic guidance eg, esophageal or endobronchial tumors or is close to highly sensitive organs.
The efficacy of brachytherapy relies on the very high radiation dose delivered directly to the tumor, close to the sources. Furthermore, there is no need for additional uncertainty margins around the clinical target volume. Indeed, if the tumor moves during the radiation procedure, the radiation source moves as well.
Treatment can be delivered within a few days compared with protracted fractionated radiotherapy schemes, and this is clinically relevant in proliferating tumors to decrease the overall treatment time, thereby improving local control by limiting tumor repopulation. Figure 1 illustrates the specificity of brachytherapy in terms of dose distribution. As very high doses are delivered, acute reactions inflammation and irritation at the treatment site are frequent and may be minor to intense, depending on the dose, the site, and the volume treated.
As for other invasive treatments, there is a risk of infection and perioperative pain. The main limitation of interstitial brachytherapy is that it is invasive, requiring a short procedure in the operating room to place the sources or the catheters. Another key point of brachytherapy is that the quality of implantation is an important parameter of the therapeutic index. Indeed, any inappropriate positioning of the sources may expose the tumor to underdosage or excessive toxicity if the sources are too close a critical organ. The importance of individual expertise and the implementation of a specific brachytherapy workflow must be appraised.
Given the logistical issues inherent to brachytherapy and the high level of expertise required for implantation, there is an increasing temptation to propose alternative techniques that are easier to implement. In international guidelines, the standard treatment for patients with locally advanced cervical cancer LACC relies on external radiotherapy combined with concurrent chemotherapy, followed by a brachytherapy application to increase focally the dose to the primary tumor.
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Other approaches, including neoadjuvant chemotherapy and radical surgery, were found to be inferior to concomitant chemoradiation plus brachytherapy in a randomized phase 3 study. Brachytherapy application consists of inserting a plastic tube within the uterine cavity and an applicator within the vaginal cavity. This insertion may be done under general or spinal anesthesia, as it requires dilatation of the cervical canal. The development of modern applicators has facilitated the implantation of needles to treat distal tumor extensions within the parametrium.
Guidelines have been written to homogenize treatment delivery, and new concepts integrating tumor regression during treatment have been implemented.enter
Those symptoms mainly include menopause and definitive sterility, as well as vaginal sequelae. Indeed, the ovaries, uterus, and potentially involved parts of the vagina are considered as part of the target volumes to be irradiated by EBRT because of a risk of tumor cell dissemination. Ongoing studies are examining how to minimize the risk of vaginal stenosis, dyspareunia, and QOL impairment. Overall survival OS was superior in patients treated with brachytherapy hazard ratio, 0. A close collaborative network between nonacademic and academic centers with expert skills in brachytherapy is encouraged to provide the highest quality of care to all patients.
Apart from cervical cancer, major indications for brachytherapy are endometrial, prostate, and breast cancer Table 1. For these tumor sites, the level of evidence for brachytherapy has come from randomized controlled studies 4 - 6 , 14 , 25 , 28 - 47 focusing not only on local control but also including OS and QOL analysis Table 2. This treatment is usually conducted through 3 to 4 fractions given on an outpatient basis. The objective is to potentially sterilize residual cells in the vaginal vault and to avoid a vaginal recurrence.
Because the irradiated volume is very small and the total dose is relatively low, this treatment is usually very well tolerated with only minor and transient acute side effects proctitis, cystitis, vaginal discharge.
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The tolerance profile of brachytherapy is clearly superior to that of adjuvant pelvic EBRT, which involves large volumes of the bowel and bladder. The detrimental effect of EBRT was mainly a consequence of bowel morbidity. Otherwise, pelvic EBRT may be still indicated to decrease locoregional recurrence. Therefore, the modern management of endometrial cancers is tailored to each specific situation and is part of a multimodal approach aimed at decreasing morbidity without jeopardizing the probability of survival. Accelerated partial breast irradiation APBI is an attractive adjuvant approach in selected patients with breast cancer.
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The decrease in late skin toxicities is relevant, in addition to the improved convenience of treatment delivery. This technique is mainly used as a boost to the prostate in combination with EBRT, but monotherapy is safe and effective as well. In case of significant urinary symptoms, surgery may be preferred.
Patients need to be involved in making treatment decisions. When surgery, external radiotherapy, and brachytherapy are deemed appropriate therapeutic options, a dedicated brachytherapy consultation is recommended to ensure that patients receive appropriate information. It is particularly important to involve urologists because they refer patients and, in some circumstances, even participate directly in the placement of seeds into the prostate.
Furthermore, their expertise may be required for the treatment of genitourinary complications. After brachytherapy implantation, acute complications include a change in the International Prostate Symptom Score and urinary retention. Chronic side effects mainly include permanent urinary symptoms and erectile dysfunction. Radiation proctitis may occur, sometimes requiring a laser to treat rectal telangiectasia. These side effects must be weighed against those of other treatment options: incontinence and erectile dysfunction for surgery and bowel symptoms for EBRT.
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Brachytherapy is appropriate as monotherapy to treat small tumors that are accessible for implantation using visual, manual, or radiological guidance Fig. Its properties make the technique optimal for conservative treatments to avoid mutilating surgery without jeopardizing the probability of a cure. Physicians from a wide range of specialties may be involved in the referral, in the placement of brachytherapy, as well as in the management of treatment sequelae. Selected examples are provided below.
Brachytherapy offers the advantage of organ preservation because the only alternative would be penile partial or total amputation Fig. This technique is part of a multimodal approach, as a circumcision is required before treatment to facilitate implantation and decrease acute side effects, and a surgical exploration of the groin sentinel lymph node procedure or lymph node dissection may be performed in the same operative time to complete radiological staging and address the regional risk.
Second cancers are among the most feared complications after radiotherapy in childhood. Although the specific impact of modern technologies is still under investigation, theoretical models suggest that IMRT may increase the risk of second malignancies as a consequence of the increase in the volume of normal tissues receiving low doses.
This approach, combining open surgery and catheter placement in the same procedure, requires a close collaboration between surgeons and brachytherapists. The purpose is to focally increase the dose while sparing the uninvolved part of the anal canal to minimize sphincter dysfunction. Needles are implanted along the anal canal through a transperineal approach, and fixed with a template at the perineal skin to keep the needles in place during the whole treatment. A retrospective analysis published in suggested that brachytherapy was the best boost modality in terms of the cumulative rate of local recurrences; however, no confirmatory, prospective study has been conducted, and this technique requires operator experience to properly define the tumor site to be treated.
A close collaboration between radiation oncologists, proctologists, and brachytherapists is crucial. Furthermore, not all patients can be treated by brachytherapy, and selection criteria should be followed to avoid or at least minimize the risk of necrosis. However, acute reactions are frequently intense and require local applications with or without analgesics for a few weeks. Brachytherapy is also indicated as postoperative treatment in patients with tongue carcinoma who have risk factors for local relapse perineural involvement, lymphovascular space invasion, close margins to avoid the side effects of external radiotherapy irradiating the whole oral cavity and thus avoiding xerostomia.
Brachytherapy is strongly challenged by reconstruction surgery for small tumors, and increasing numbers of patients are referred to brachytherapy teams at the time of local relapse or for adjuvant treatment because of close margins. To avoid adding the morbidity of surgery and that of brachytherapy, a multidisciplinary discussion should occur before any treatment is recommended and should include radiation oncologists who are familiar with brachytherapy or are working in an expert collaborative network for referring selected patients.
The role of otolaryngologists is crucial to properly refer patients for brachytherapy as well as for comprehensive pretreatment and posttreatment endoscopic evaluations. The next crucial step in optimization is to personalize treatment objectives to individual patients and tumor characteristics, considering biomarkers that reveal intrinsic radiosensitivity as well as tumor microenvironment physiology to guide treatment delivery.
No independently validated, specific blood or tumor biomarker exists for brachytherapy, and most available data have focused on a strategy that may or may not have included brachytherapy. Recent retrospective data have suggested that tumor volumetric reduction after chemoradiation may be used to preferentially guide the optimal boost dose in patients treated for LACC, thus reinforcing the rationale for increasing the dose in poor responding patients.
A threshold seems to have been reached in the ability to improve outcomes through dose escalation. Numerous developments in functional imaging provide opportunities to improve brachytherapy by considering tumor heterogeneity at the macroscopic scale. For example, tumors with an infiltrative shape respond less favorably to chemoradiation than expansive tumors equivalent in size. This may allow for more accurate volume delineation to test functionally guided dose escalation in cases of resistant tumors or in reirradiation, which is an increasing research area for PCa.
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