Eur Arch Otorhinolaryngol (2016) 273:2707–2715 DOI 10.1007/s00405-015-3794-3
HEAD AND NECK
Intensity modulated perioperative HDR brachytherapy for recurrent and/or advanced head and neck metastases Ingo U. Teudt1 • Gyo¨rgy Kova`cs2 • Matthias Ritter3 • Corinna Melchert2 Tamer Soror2 • Barbara Wollenberg3 • Jens E. Meyer4
•
Received: 2 May 2015 / Accepted: 5 October 2015 / Published online: 23 October 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract Recurrent neck metastases following surgery and full dose adjuvant radiotherapy of squamous cell head and neck cancer remain a clinical challenge. After revision neck dissection and chemotherapy re-irradiation dosage is often limited and survival prognosis deteriorates. Here, adjuvant high-dose rate intensity modulated perioperative brachytherapy (HDR IMBT) offers a second full radiation dose with a limited volume of normal tissue radiation in the neck. In this retrospective study patients were identified who underwent revision surgery and perioperative HDR IMBT for recurrent neck metastases. Survival rates were estimated and the scarce literature on interstitial brachytherapy of the neck was reviewed. From 2006 to 2014, nine patients were treated for recurrent or palliative neck metastases using salvage surgery and HDR IMBT. Eight patients received previous surgery and external beam radiotherapy with or without chemotherapy. Two and five year overall survival was calculated to be 78 and 67 %, respectively. HDR IMBT is a salvage treatment option for selected cases in the neck following surgical revision or
I. U. Teudt and G. Kova`cs contributed equally to the article. & Ingo U. Teudt
[email protected];
[email protected] 1
Department of Otolaryngology, Head and Neck Surgery, Asklepios Klinik Altona, Paul-Ehrlich-Strasse 1, 22763 Hamburg, Germany
2
Interdisciplinary Brachytherapy Unit, University Hospital Schleswig-Holstein, Luebeck, Germany
3
Department of Otolaryngology, Head and Neck Surgery, University Hospital Schleswig-Holstein, Luebeck, Germany
4
Department of Otolaryngology, Head, Neck and Plastic Surgery, Asklepios Klinik St. Georg, Hamburg, Germany
last-line treatment strategies. In the literature and this small cohort radiation toxicity and the risk of ‘‘carotid blow-out’’ seemed to be low. Keywords Head and neck cancer Recurrent neck metastases Intensity modulated brachytherapy
Introduction Over the last several decades significant efforts have been directed at optimising treatment regimes for head and neck squamous cell cancer. Whereas early-stage disease receive single-modality treatments, advanced-stage tumors are managed by multimodality therapy. In addition to surgery and chemotherapy, external beam radiotherapy (EBRT) plays an important role in this multimodality therapy, with application and benefit being well established for all locations of the head and neck region [1–3]. Despite the success achieved, recurrence rates for cancer above the clavicle are reported as high as 24 % [4, 5]. Locoregional failure is still the predominant pattern of failure and is the most common cause of death in head and neck cancer patients [6]. Since most of the patients already received full dose EBRT, re-irradiation with a second course of EBRT is often of limited feasibility due its high rate of acute and late toxicities. Although attempts have been made to decrease toxicity for re-irradiation using radiation techniques such as intensity-modulated radiotherapy (IMRT) or three-dimensional radiotherapy, occurence of acute and late toxicities remains substantial [7]. Today, high-dose rate intensity modulated brachytherapy (HDR-IMBT) has gained actuality in the treatment of head and neck cancer [8]. It offers the potential to deliver
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radiation with rapid dose fall-off outside the target volume, which minimizes injury to skin, bones, muscles and the surrounding neurovascular structures. This potential is of great value in the head and neck region given its density of important, functional anatomic structures. Interstitial perioperative IMBT is well established as part of a multimodality treatment regimen for oropharyngeal cancer and for tumors of the nasopharynx and oral cavity [9, 10]. Recently, promising results have also been reported for perioperative IMBT in the treatment of sinonasal carcinoma and tumors invading the skull base [11–14]. Meanwhile, perioperative IMBT is also used for the treatment of recurrent head and neck cancer [10, 15–20]. Next to perioperative fractionated IMBT some institutions use intraoperative single shoot HDR-irradiation (HDRIORT) for the management of locoregionally recurrent head and neck cancer. Here, radiation is applied in one session during a surgical break. However, a shielded operation room (OR) is needed and all personnel has to clear the OR during radiation delivery [21, 22]. Furthermore, the biological advantage of fractionated radiation delivery is not available. In addition to its use in local recurrences, such as the oropharynx, brachytherapy has been used for regionally recurrence in the neck. However, literature on using perioperative HDR-IMBT in neck metastases is scarce and its implementation in treatment strategies are not widely used. In conjunction with salvage or revision neck dissection brachytherapy applicators (plastic tubes) often have direct contact, or at least close proximity, to the carotid artery. The fear of harm to this vital structure (‘‘carotid blow out’’) may be one reason why physicians opt for perioperative IMBT less often in recurrent metastases of the neck. Nowadays, an improvement of prognosis with low toxicity is anticipated for patients receiving perioperative HDR-IMBT and neck dissection in second-line or palliative treatment regimens. The objective of this manuscript was to assess the feasibility and outcome/toxicity of combined therapy with perioperative IMBT and salvage neck dissection at a single institution for the management of recurrent and palliative neck metastases.
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Terminology Criteria for Adverse Events (CTCAE). All results were compared to actual findings in the literature. The retrospective study was approved by the institutional ethic committee (protocol 11-065A). Procedure of perioperative intensity modulated brachytherapy (IMBT) Intraoperative implantation of inactive brachytherapy applicators Surgery of the neck was performed by the surgeon under surveillance of the brachytherapy expert to achieve optimal applicator placement. Following surgery, an adequate number of applicators were implanted with the necessary geometry into the tumor bed, fixed to negative or positive margins of the resection with resorbable sutures (Fig. 1b). If necessary, surgical clips were set to visualise certain areas on the planning CT images. The geometry and anatomic placement of the applicators was chosen interdisciplinary, to ensure an optimised radiation dose distribution and reliable surgical procedures: Tube distances (in the range of 5–12 mm) were enlarged in regions requiring higher radiation doses around the tubes and decreased if surrounding sensitive structures (such as the carotid artery or cranial nerves) necessitated a lower local radiation dose. For optimised and intensity modulated dose planning at the carotid artery surface, the artery was always paralleled by the applicators. If the vessel’s adventitia needed to be removed the carotid artery surface was covered with a ha¨mostyptikum fleece (TABOTAMP, Ethicon, Germany) in an effort to add a few millimeter distance between the tubes and the vessel in order to avoid artery contact with high surface doses around the tubes which were fixed in their position by single sutures over the target volume. After wound closure, all applicators were fixed to the skin with sutured radiopaque buttons (Fig. 1b). Following applicator implantation antibiotics were started intravenously to prevent wound infection, and were continued as oral therapy during the period of radiation. Postoperative IMBT
Patients and methods At the analysed institution patients with advanced-stage head and neck cancer are offered a multimodality therapy. Treatment plans entail surgery, perioperative HDR-IMBT, EBRT and chemotherapy. From this group of patients all charts were reviewed to identify those treated for recurrent neck metastases using surgery and perioperative HDRIMBT. The cohort was then analysed for overall survival (OS) and radiation toxicities according to the Common
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The total radiation dose of IMBT was chosen as adjuvant full dose re-irradiation after previous EBRT and salvage neck surgery. Evaluation of proper applicator placement was performed by cranial helical CT imaging (2 mm slice thickness with overlapping images) and documented also as orthogonal radiographs (Fig. 2b). Radiation treatment planning was based on cCT with or without MRI slicematching simulation data in a three-dimensional virtual reconstruction setting by the use of dedicated treatment planning software packages (BrachyVision, Varian and
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Fig. 1 A 46-year-old patient with recurrent neck metastasis following neck positive oropharyngeal cancer treated by surgery and EBRT. a The preoperatively planned tumor resection and reconstruction via myocutaneous pectoralis major flap. b The intraoperative situs after
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tumor resection and brachy tube placement. Note the two BT paralleling the carotid artery. The pectoralis major flap is ready for reconstruction of the defect
Fig. 2 CT scans after surgery and brachytherapy tube insertion of the same patient depicted in Fig. 1. a 3D reconstruction of the patients neck including planning and intensity-modulated visualisation of the calculated isodoses for brachytherapy. b The same patient in a transverse CT plane
Oncentra Brachy, Elekta). With the use of cross-sectional imaging data, applicator positions were digitized in the volume manually, whereas regions of interest (carotid artery or cranial nerve, etc.) were contoured in a manual, semiautomatic or automatic mode (Fig. 2a). No Inverse Planning Algorithm was used for IMBT. Manual volume-optimised target doses were calculated for 2 9 2.5 Gy/day high-dose rate (HDR) remote after loading with an initial source strength of 370 GBq. HDRIMBT was delivered twice a day with interfraction intervals of at least 6 h. The prescribed dose per fraction was 2.5 Gy and the dose-nonhomogeneity ratio (DNR = V150/V100) never exceeded 0.42. The prescribed total IMBT radiation maximum dose was 30 Gy in 3–6 treatment days (range 15–30 Gy, average 27 Gy). The reference isodose was defined within a maximum of 10 mm lateral distance from a tube, and the maximum allowed plastic tube surface dose was 49 the reference isodose value. Further important constraints were the irradiated volumes: no more than 50 % of the carotid
artery wall was irradiated to minimise the length of highdose areas along the vessel wall. More details regarding the used treatment planning procedure were previously published by Siebert et al. [17]. Due to the technical potential of a stepping source and individual intensity modulated treatment planning, cold spots in the dose distribution were placed to critical structures and hot spots to intraoperatively verified positive tumor margins or residual tumor mass. Thus, the inhomogenic dose distribution within a target volume was manually adapted to the given anatomic situation. The intraoperative subvolume definition was based on clinical findings, opinion of the surgeon and results of frozen histology. If necessary, surgical clips were set to visualise certain areas on the planning CT images. In all cases the applicator implanting brachytherapy expert performed the manual dose volume optimisation for the target subvolumes. IMBT was started 4–12 days after operation (average 7 days). No treatments were done on Saturdays and Sundays or on public holidays.
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65 Neck, dead 21 SCC squamous cell carcinoma, surg surgery, ND neck dissection, Ctx cetuximab, IABTprim 30 Gy on primarius
Initial treatment was palliative Neck 50 Deb.-surg ? ND ? EBRT ? IABT ? Ctx CUPmetastasis SCC Male K.
66
58 93
119 No failure, allive
Liver metastases, dead Oropharynx, allive 30 15
30 Re-ND ? IABT ? Ctx
Re-ND ? IABT ? Ctx Re-ND ? EBRT50 Gy ? IABT ? Ctx Neck Neck
Neck 66
70 – EBRT ? ND ? Ctx Surg ? ND
EBRT ? ND ? Ctx Oropharynx
Oro/hypopharynx Oropharynx SCC SCC
SCC 41 Male
Male Male
L.
S. D.
38 63
7
106 No failure, allive 30 Re-ND ? IABT ? Ctx Neck 60 ND ? EBRT CUPmetastasis 43 Female N.
SCC
1 Heart attack, dead
Sinonasal, dead 30
30 Re-ND ? IABT
Re-ND ? IABT Neck
Neck 60
70 EBRT, surg ? ND ? IABTprim
Surg ? ND ? EBRT ? Ctx Hypopharynx
Sinonasal SCC
SCC 63
53
Male
Male
S.
50
Male
Male
G.
M.
62 Larynx, dead
No failure, allive 30
25 Re-ND ? IABT
Re-ND ? IABT Neck
Neck 59
60 Surg ? ND ? EBRT
Surg ? ND ? EBRT Larynx
Salvage treatment Site of 1st failure EBRT (Gy) Initial treatment Primary site
J.
The history of initial treatments among the analysed patient cohort was quite heterogeneous. Some of the patients were referred from other clinics or presented with first- or second-line failures to our interdisciplinary team. Seven patients had been treated previously with an average dose of 64 Gy EBRT, range 59–70 Gy. Four
Histology
Initial treatments
Age (years)
Between January 2006 and January 2014 nine patients were identified who underwent surgery and perioperative HDRIMBT for recurrent or palliative neck metastases. Patient characteristics and the pathologic diagnoses are shown in Table 1.
Sex
Results
ID
Follow-up time was defined as the beginning of perioperative IMBT until the last patient contact or event. For censored patients, the last date of contact or death was used in the survival estimates. The survival time was calculated from the beginning of IMBT to last contact or death. All estimated survival rates were calculated by the Kaplan and Meier method using GraphPad Prism 5.01 California, USA [23]. Due to the small number of patients (n = 9) no statistical analysis was performed with respect to age, gender, localisation, histology, primary treatment, UICC stage and tumor grade. Also in-field control or failure were not calculated since the number for each variable was too small to achieve meaningful results.
Table 1 The characteristics and history of treatments of patients with cervical recurrence or palliative neck disease
Statistics
IABT (Gy)
Patients who lived close to the institution were followed-up regularly beginning 1 month after initial treatment, followed by 3 months intervals within the first 2 years and 6 months intervals over the remaining 3 years. Follow-up data were extracted from the patient charts. Patients living a far distance from the institution were followed by local head and neck departments and their local physicians. In all cases, follow-up data were recently updated. Questionnaires regarding survival and health condition were sent to the responsible physician of each patients.
Oropharynx
Follow-up
SCC
Site of 2nd failure
After completion of IMBT all applicators were removed under general anaesthesia by a head and neck surgeon so as to be prepared for potential complications such as extensive bleeding.
57
Survival (month)
Applicator removal after completing radiation
85
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SCC
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patients received either induction or concomitant chemotherapy. Previous neck dissection was performed in eight patients. The median time interval to recurrence in the neck was 11 months (range 4–19 months). All initial treatments are presented in Table 1. Patient K presented with a newly diagnosed palliative N3 metastasis of a carcinoma of unknown primary (CUP). There was no previous treatment of the disease.
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Two patients had a recurrence in the neck after 62 and 65 months. The remaining two patients died of distant metastases (liver) and recurrence of the primarius (sinonasal cancer), respectively. Today, three patients are reported to be tumor-free. One patient is still alive but developed recurrent oropharyngeal cancer after 58 months and recently bladder cancer. Complications
Salvage treatments Depending on the size and location of the recurrent neck metastases the resection could be closed primarily in most cases (n = 7). In larger defects, myocutaneous flaps were used for wound closure (n = 2). Especially when using brachytherapy, the incidence of skin necroses at the surgical field must be avoided. Myocutaneous flaps such as the pectoralis major flap offer ideal tissue grafting to perform the perioperative HDR-IMBT safely (Fig. 1a, b). The two patients who had no previous EBRT received a protocol of surgery, perioperative IMBT, complementary EBRT and concomitant chemotherapy with Cetuximab. One of the patients was not treated with curative intent. All actual treatments are summarised in Table 1.
One patient died of a heart attack one month after receiving IMBT. Due to a known history of coronary heart disease the cause of death was not clearly related to IMBT. Using the Common Terminology Criteria for Adverse Events (CTCAE), early toxicities were reported in four patients and were limited to local edema and skin infection (grades I–II) [24]. There were no intra- or perioperative deaths. Late toxicities occured in one patient who still suffers from an accessory nerve disorder at the implantation site (grade II). There was no wound breakdown with skin necrosis and no serious harm to the myocutaneous flaps or carotid artery (‘‘carotid blow out’’).
Outcomes
Discussion
The mean follow-up time for all patients was 66 months (range 1–119 months). According to the Kaplan–Meier method, 2 and 5 years overall survival (OS) estimates were calculated to be 78 and 67 %, respectively (Fig. 3). The OS rate at the end of this study was 44 %. The median survival of the cohort was 65 months. The pattern of locoregional failure is provided in a descriptive way since patient numbers are too small for meaningful statistics. Five of nine patients died during the survey. The shortest survival was 1 month (heart attack).
The treatment of recurrent neck metastases in patients suffering from head and neck cancer remains challenging. Depending on tumor size, invasion of vital structures and the former type of neck dissection, patients usually are treated by revision neck dissection. After surgery a second course of EBRT is often limited since the patient already received full dose EBRT in first line therapy, and radiation toxicity does accumulate. Chemotherapy alone often remains of low benefit with poor response and sustainability [25]. In this scenario perioperative brachytherapy offers a valuable treatment option, especially for recurrent neck metastases following previous neck dissections. Most reports utilized low-dose rate (LDR) permanent- or after loading techniques. The literature on perioperative HDRIMBT as used in this review remains scarce. Thus, our experience was published despite the low number of patients treated for recurrent neck metastases with perioperative HDR-IMBT and neck dissection (n = 9) and the low statistical relevance. In this regard, the authors believe that it is important, when discussing treatment strategies on interdisciplinary tumor board meetings, to remind head and neck surgeons of the promising and well-established treatment options of perioperative HDR-IMBT. For the use of brachytherapy in neck metastases, Choo et al. differentiated four indications. First, patients with
Fig. 3 Depicts the OS function of patients treated with IABT and surgery for recurrent or palliative head and neck metastases
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recurrent or persistent neck disease after initial EBRT can be treated by salvage surgery and brachytherapy. Second, in patients contraindicated for neck surgery brachytherapy can be used as a local radiation boost following EBRT. Third, brachytherapy can be used alone with curative intent for small isolated neck recurrences. Finally, brachytherapy may be used for the palliation of gross neck disease to reduce pain. Similar to the study presented here, Choo et al. reviewed nine patients dedicated to the first group. The patients received neck dissection and intraoperative 192 Iridium low-dose rate (192Ir-LDR) brachytherapy doses between 40 and 60 Gy. At the end of his survey three patients (33 %) were alive with 6, 16 and 27 months follow-up and six patients died within 10 months mostly with distant metastases. One case of 12th cranial nerve palsy and three patients with delayed wound healing grades I–II were reported. However, histologic entities and tumor stages within this group were not clearly indicated [26]. Wibault et al. treated 164 patients for neck relapse, again using 192Ir-LDR BT with or without surgery. The mean OS was 8.8 months only [27]. Other groups reported 2 years OS rates between 38 and 20 % for 192Ir-LDR BT with surgery [28–30] and 2 years OS rates between 28 and 13 % for 192Ir-LDR BT alone [31–33]. A comprehensive table with all previous studies using LDR BT in recurrent lymphadenopathy is available at Tselis et al. [34]. Recently, institutions started to use 192Ir-HDR-BT for the treatment of recurrent neck metastases. Kolotas et al. reviewed a series of 49 patients, becoming the first to report on CT-guided interstitial 192Ir-HDR-BT for recurrent cervical lymphadenopathy. All patients received previous EBRT and 73 % underwent initial surgery. The 2 year OS rate was 31 % and the intention to treat palliative. Tumor entities were inhomogen with squamous cell-, adenoid-cystic- and adenocarcinoma [35]. A few years later the same institution published a review of 74 inoperable patients receiving palliative CT-guided interstitial 192 Ir-HDR-BT for recurrent neck metastases. This time the 2 year OS declined to 19 %. Most of the histologies (83 %) were squamous cell carcinoma. Primary tumor sites were distributed to all head and neck regions [34]. Both authors excluded debulking or salvage neck dissection in their palliative treatment regime. In contrast, Pellizzone et al. analysed their treatment outcome in 21 patients where interstitial 192Ir-HDR-BT was combined with salvage surgery. Inclusion criteria were recurrent cervical cancer with local control of the primary site, squamous cell carcinoma, surgical resectability and no distant metastasis. Fifteen patients underwent previous EBRT. The 5 and 8 year OS rate was 50 and 43 %, respectively. It is noteworthy that surgical clear margins (R0-resection) could be achieved in 85 % of this collective. This fact was significantly correlated with the OS rate [36].
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The M.D. Anderson Cancer Center reviewed 22 patients for cervical recurrences of head and neck cancer. All of them previously received EBRT with average dosage of 65 Gy, and 46 % had additional surgery. The intention to treat was curative with salvage neck dissection and 192IrHDR-BT in all patients. OS survival rates were 57 and 46 % for 2 and 5 years after irradiation, respectively. 20 patients suffered from squamous cell carcinoma and two from different tumor entities [37]. Although, the actual study cohort is small and represents a heterogeneous group of patients, the observed OS rate after 5 years is close to other studies using 192Ir-HDR-BT and salvage surgery. As depicted in Fig. 3 the OS rate function declines at 5 years and 5 months to 44 % and is in line with the observed 5 year OS reported by the group of Pellizzone and the M.D. Anderson Cancer Center. Compared to LDR-BT in the past, with OS rates between 38 and 20 % as shown above, the recently published results including our actual survey using 192Ir-HDRBT seem to reveal a distinct improvement in survival with 2 year OS rates between 78 and 50 % after radiation [36, 37]. However, the large heterogeneity regarding tumor and previous treatment characteristic makes comparisons between survival rates within the available literature very difficult. In Table 2 a summary of previous studies using 192 Ir-HDR-BT in recurrent lymphadenopathy is provided. In the actual study, early and late toxicities were low and did not exceed grade II of the CTCAE classification. Since most of the patients underwent previous EBRT and surgery, the retrospective study design made it difficult at times to determine if toxicities were related to brachytherapy or to the first line treatment. In the case of accessory nerve disorder at the BT implantation site the patients sequelae might also be caused by the surgical procedure of salvage neck dissection, as opposed to IMBT. The lack of skin and myocutaneous flap necrosis is consistent with the literature and implies avoiding harm to the carotid artery. Skin necrosis at the surgical field has to be avoided at all times! In one of the oldest studies (1965–1971) on BT in neck metastases, late carotid exposure followed by lethal ‘‘carotid blow out’’ was noted in 11 % of cases. All patients had pre-existing skin ulceration above the metastases, and no surgical flap coverage was performed [27]. Thus, skin ulceration was felt to be a contraindication for BT. Nowadays, with the familiar use of pectoralis major muscle (PMJ) flaps in nearly every head and neck clinic ‘‘carotid blow outs’’ following neck dissection and BT have not been reported in the last 20 years [26, 28, 36, 37]. Zelefsky et al. assumed exposure and subsequent infection of the carotid artery to be the mechanism for vessel break down, as opposed to the proximity between artery and BT radiation source [29]. In fact studies using radiation sources
Eur Arch Otorhinolaryngol (2016) 273:2707–2715 Table 2 The available literature about Study group
Year
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192
Ir-HDR-BT in recurrent neck metastases is listed
Patients (n)
Actual treatment
First line therapy
BT-type
Mean dose (Gy)
EBRT (%)
ND
EBRT (%)
ND
Chemo (%)
OS (2; 5 years)
Acute and late toxicity (grade)
Kolotas et al. [33]
2006
49
192
31.5
0
0 %, CTguided
100
73 %
53
31 %; nn %
II 13 %, III 4 %
Teslis et al. [32]
2011
74
192
30
0
0 %, CTguided
100
58 %
67
19 %; nn %
III–IV 13 %
Pellizzon et al. [34]
2006
21
192
24/40
5
63 %; 50 %
I–II 19 %, III–IV 19 %
Kupferman et al. [35]
2007
22
192
Teudt et al.
2015
9
192
lr HDRBRT lr HDRBRT lr HDRBRT lr HDRBRT lr HDRBRT
100
100 %
72
nn
52
0
100 %
100
46 %
50
57 %; 46 %
I–II 14 %, III–IV 27 %
27
0
100 %
89
77 %
45
78 %; 67 %
I–II 45 %
All previous studies using LDR-BT are tabularly available in Tselis et al. 2011 [34] ND neck dissection, chemo chemotherapy, nn not provided
near the canine carotid artery found no complications with doses of 150 Gy from 125Iridum and with 60 Gy from 192 Iridium implants [38]. Additional support was found by Stafford and Dearnaley who treated ‘‘inoperable’’ neck nodes using surgical clearance and postoperative BT. After observing tissue necrosis at three patients treated with permanent 192Ir after loading catheters, no further soft tissue complications were found in the remaining five patients when myocutaneous flaps were used for defect resurfacing [39]. Similar findings were reported by Cornes et al. who compared the complication rates in 13 patients treated with debulking surgery of neck metastases and BT with 26 patients receiving additional pedicle flap (mostly deltopectoral and pectoral flap) coverage. They described a reduction in severe radiation toxicity rates from 46 % in the first group versus 12 % in the reconstructed group [28]. Geiger et al. from Yale University retrospectively analysed 93 patients having flap reconstructions at the time of BT implant following surgery for head and neck cancer. 49 % had a prior history of radiation (EBRT or previous BT) to the site of reconstruction, and 74 % of patients had undergone prior surgery. In 33 % of patients, hardware (screws or plates) was used intraoperatively to reestablish mandibular continuity. They stated that free flaps may pose a higher complication risk compared to pedicle flaps and that the presence of mandibular hardware following BT was associated with more complication and return to the operating room [40]. In summary, myocutaneous flaps like the pectoralis major flap offer ideal tissue grafting to cover brachytherapy tubes and avoid skin necrosis in neck metastases safely. With the use of HDR-BT and optimised image adapted treatment planning that ensures the correct position of
radiation sources and dosimetric constraints to be fulfilled, rates of severe complications have declined. Although brachytherapy and stereotactic radiation (SBRT) in head and neck cancer was proven as more successful technology compared to IMRT in local dose escalation (boost) situations [41], there are no literature data comparing different radiation technologies on the neck—especially in recurrent disease. From a physical point of view brachytherapy offers the lowest normal tissue radiation volume, which is an essential advantage in the treatment of previously irradiated cases. Furthermore, compared to target definitions based on postoperative CT imaging intraoperatively performed and marked radiation therapy target definition is more accurate. Additional advantages of perioperative HDR brachytherapy are: less tumor cell to kill with radiotherapy due to surgical debulking, no intra- and/or interfraction target movement, lower total treatment time and the potential of large dose inhomogeneities within a very small volume due to the steep dose fall-off of the used radioactive sources [42].
Conclusion Salvage surgery with perioperative HDR-IMBT has become a feasible and safe treatment option for recurrent neck metastases. OS seems to improve with manageable toxicities even after previous full dose EBRT. Prospective clinical trials and further studies, eliminating the heterogeneity of patients, tumor, and treatment characteristics are warranted, but unlikely given the rare usage of this treatment option. The available literature discussed here and the carefully weighted experience of our single institution will hopefully encourage colleagues in the field to consider
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perioperative HDR-brachytherapy for the challenging situation of tumor recurrence in the neck. Acknowledgments The authors thank Eva Golabek and Adam Navel for editing the manuscript.
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14.
Compliance with ethical standards Conflict of interest of interest.
The authors declare that they have no conflict
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. However, due to the retrospective type of the study no formal consent was required.
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Statement on the welfare of animals This article does not contain any studies with animals performed by any of the authors.
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