Brachytherapy

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Re-irradiation with interstitial pulsed-dose-rate brachytherapy for unresectable recurrent head and neck carcinoma Vratislav Strnad*, Michael Lotter, Stephan Kreppner, Rainer Fietkau Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany

ABSTRACT

PURPOSE: To assess the long-term results of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy combined with simultaneous chemotherapy in selected patients with recurrent head and neck tumors not amenable to salvage surgery. METHODS AND MATERIALS: A total of 51 patients with recurrent head and neck cancer were treated with interstitial PDR brachytherapy. Forty patients (78%) had salvage brachytherapy alone using a median total dose of 60 Gy. Salvage brachytherapy in combination with external beam therapy was performed in 11 patients (22%) using a median total dose of DREF 5 27 Gy. Simultaneously with the PDR brachytherapy, a concomitant chemotherapy was administered in 35/51 (69%) of patients. The analysis was performed after a median followup of 58 months. RESULTS: Local control rates calculated according to KaplaneMeier after 2 and 5 years were 71% and 57%, respectively. Comparing results of salvage PDR brachytherapy with or without simultaneous chemotherapy, the 5-year local recurrence-free survival rates were 78.9% vs. 38.5% ( p 5 0.01), respectively. No other patient or treatment-related parameters had a significant influence on treatment results. A total of 9/51 (17.7%) and 6/51 (11.8%) patients developed softtissue necrosis or bone necrosis, respectively, but only 2% of patients required surgical treatment. CONCLUSIONS: PDR interstitial brachytherapy with pulse doses between 0.4 and 0.7 Gy/h/24 h with simultaneous chemotherapy is an effective and safe option for curative therapy in selected patients with head and neck cancer in previously irradiated areas, which are not suitable for salvage surgery. Ó 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Keywords:

Re-irradiation; Head and neck cancer; Interstitial brachytherapy; PDR brachytherapy; Salvage brachytherapy; Local recurrence

Introduction Despite aggressive multimodality treatment protocols used in first-line treatment, a significant proportion of head and neck cancer patients develop locoregional recurrences typically during the first years of followup. Patients with recurrent head and neck cancer or a second primary tumor occurring in a previously irradiated area have generally a very poor prognosis. If surgery is not an option, the curative treatment possibilities are exceptionally limited (1, 2). Usually, the setting of re-irradiation is palliative and as

Received 24 June 2013; received in revised form 26 August 2013; accepted 16 October 2013. * Corresponding author. Department of Radiation Oncology, University Hospital Erlangen, Universit€atsstr. 27, 91054 Erlangen, Germany. Tel.: þ 49-9131-8533419. E-mail address: [email protected] (V. Strnad).

a consequence the results of such treatments are very disappointing (3, 4). However, since 1990, it has been demonstrated through several studies that a multimodality approach of re-irradiation with simultaneous chemotherapy is feasible with long-term local control for a fraction of patients (5e14). The main advantage of interstitial brachytherapy is an extremely steep dose gradient between the prescription dose encompassing the tumor area and the surrounding healthy structures as the mandible, skin, healthy parts of the tongue or of floor of the mouth. These quality characteristics make it possibledat least theoreticallydto provide excellent protection to these organs and structures to an extent and quality that would be unattainable using techniques of external beam radiation therapy. In addition to this fact, there are further properties of brachytherapy, which make this technique highly suitable for the purposes of re-irradiationdnamely its high flexibility, high versatility, excellent precision, very good quality assurance,

1538-4721/$ - see front matter Ó 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.brachy.2013.10.008

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and reproducibility resulting from its lack of dependence on patient or organ motions. All these attributes of brachytherapy are excellent preconditions for good results of interstitial brachytherapy as a salvage treatment modality for recurrent head and neck tumors. Unfortunately, the majority of recurrent head and neck cancers are not appropriate candidates for brachytherapy alone because re-irradiation of local recurrences with brachytherapy is suitable only for small volume recurrent disease and for technically accessible locations of tumor recurrences. A number of publications from the last decades (1, 5, 15e18) as well as our own first results (14, 19) have shown that interstitial salvage brachytherapy is feasible and could potentially be a curative option for these patients. The aim of the present analysis was to assess the longterm results of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy combined preferably with simultaneous chemotherapy in a group of selected patients where salvage surgery was not possible.

Patients and methods Patients Between 1999 and September 2008, a total of 51 patients with biopsy proven, recurrent head and neck cancer not amenable to salvage surgery were treated with interstitial PDR brachytherapy in our department. Criteria for eligibility for protocol-based salvage brachytherapy  simultaneous chemotherapy and interstitial hyperthermia were as follows: histologically confirmed recurrent carcinoma of the head and neck region with no evidence of distant metastasis, tumor size and location suitable for brachytherapy techniques, good performance status, and radiation therapy completed more than 3 months ago. In patients with relevant comorbidities, which presented a contraindication to chemotherapy, we refrained from simultaneous chemotherapy. Likewise, for additional interstitial hyperthermia, we strictly selected patients with good compliance only. Before diagnosis of the tumor recurrence, all patients had in the context of their previous antitumor treatment received radiation therapy up to a total dose between 60 and 76 Gy (median 65 Gy) with or without chemotherapy. Re-irradiation All patients were treated with interstitial PDR brachytherapy with or without external beam radiation therapy. The implant method was described by us in detail earlier (14, 20). The dose specification was done in all cases according to ICRU 58 (Paris system). A dose per pulse (dp) of 0.40 to 0.70 Gy (median 0.55 Gy) was given up to a median total dose of 57 Gy (range between 12 and 66.3 Gy). The pulses were delivered for 24 h per day, night and day, with a time interval of 1 h between two pulses.

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Tumor response and toxicity All patients underwent repeated examinations during and after therapy for evaluation of tumor response and side effects. Following the end of therapy, patients were followed at 3-month intervals for 24 months and thereafter at 6-month intervals for at least a further 60 months to analyze late side effects, local control, and survival. The side effects were scored according to the European Organisation for Research and Treatment of CancerdRadiation Therapy Oncology Group Criteria and the Lent Soma criteria (21). Statistical considerations The primary end point of the analysis was to analyze local tumor control rate and late side effects at 5 years. Additional end points were disease-free and overall survival after 5 years. The median followup was calculated from the first day of re-irradiation to the date of last followup. Data management and statistics were carried out with PASW Statistics for MS Windows (SPSS Inc., Chicago, IL), release 21.0.0. For statistical comparisons between groups, the ManneWhitney U test and Pearson’s Chisquare test were used, as appropriate. Survival probability was estimated using the KaplaneMeier method (22), using the log-rank test and Cox regression multivariate analysis to compare two or more groups.

Results Patient population The median followup of the patients was 58 months (24e76 months). The median time interval between the first and second radiation therapy, that is, retreatment with brachytherapy, was 27 months (range, 6e254 months). Eleven of 51 (22%) patients were treated with second primaries and 40/51 (78%) with recurrent tumors. Detailed patient characteristics with regard to tumor site and tumor stage (Table 1) show that the majority of the patients had carcinoma of the tongue (61%) and $T2 tumors (90%).

Salvage brachytherapy The median implant volume as measured by the volume of the reference isodose was 34.1 cm3 (range, 7.2e77.1 cm3). Further documented brachytherapy parameters included the V150, the dose non-uniformity ratio, coverage index (V100), and the D90. Their median values were 7.6 cm3, 0.25, 93.8%, and 99.2%, respectively. Forty patients (78%) had salvage brachytherapy alone with a median total dose of 60 Gy. Salvage brachytherapy in combination with external beam therapy was performed in 11 patients (22%) with a median total dose of DREF 5 27 Gy. Here, the brachytherapy was administered

V. Strnad et al. / Brachytherapy Table 1 Patient characteristics

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Therapy efficacy

Characteristics

Number of patients, n (%)

Age Gender (%) Male Female Primary tumor location (%) Tonguedmobile tongue Tonguedbase of tongue Floor of mouth Buccal mucosa Lip Nasopharynx Histology (%) Squamous cell carcinoma Sarcoma Other Grade (%) G1 G2 G3 Unknown Lymphatic invasion (%) L negative L positive Unknown Stage (%) rT1 rT2 rT3 rT4 rTx rN0 rNþ rNx

58.9 y (range, 43e81 y) 38 (74.5) 13 (25.5) 16 20 8 2 3 2

(31.4) (39.2) (15.7) (3.9) (5.9) (3.9)

48 (94.1) 1 (2.0) 2 (3.9) 4 24 18 5

(7.8) (47.1) (35.3) (7.8)

10 (19.6) 4 (7.8) 37 (72.5) 5 23 8 6 9 33 13 5

(9.8) (45.1) (15.7) (11.8) (17.7) (64.7) (25.5) (9.8)

after a median of 7 days following external irradiation. External beam radiation was performed up to a median reference dose of 46 Gy (range, 28e67 Gy). Simultaneously with the PDR brachytherapy, a concomitant chemotherapy was administered in 35/51 (69%) of patients. From Day 1 to Day 5 of PDR brachytherapy, all 35 patients received one course of cis-platinum (20 mg/m2) or carboplatin (AUC1) as short intravenous infusion each day. In 23/35 patients, the platin-based chemotherapy was supplemented with 5-Flourouracil 800 mg/m2 as continuous infusion for 120 h. In 4/35 patients, chemotherapy regimens with Cisplatin/Paclitaxel or Cisplatin/Mitomycin were used for individual reasons. Additionally, 17/51 (33%) patients with good compliance were treated also with a single session of interstitial hyperthermia right after the PDR brachytherapy was finished. Interstitial dipole antennas (6e11, Median 7) were used to deliver therapy, and multipoint temperature sensors were used to measure the temperature. Each patient was maintained at the target temperature for a median of 60 min. The median temperature attained was 42.0 C. All the patients received the whole intended course of salvage PDR brachytherapy  simultaneous chemotherapy and hyperthermia. There were no treatment-related deaths.

In 41/51 patients (80.4%) after a median followup of 58 months, stable local tumor control was observed. The median time to local failure was 9 months, and the majority (2/3) of local recurrences were observed within the first 12 months (Fig. 1). Local control rates calculated according to KaplaneMeier after 2 and 5 years were 71% and 57%, respectively (Fig. 2). The 5-year disease-free survival was 60%, and only 13/51 patients (25.5%) were alive at the time of analysis. Detailed analysis of causes of death shows that 4% of patients died from other tumor, 20% died from metastases, and 37% from other causes. When comparing patients treated for second primaries (14/51) and patients with recurrent tumors (37/51), we found no difference in 5-year local recurrence-free survival rates (72% vs. 70%, respectively; p 5 0.72). Similarly, we found no statistically significant difference in the probability (neither with the log-rank test nor in multivariate Cox proportional hazards regression analysis) of local recurrence in patients subgrouped by different brachytherapy quality parameters, by anatomic site of the tumor, tumor size, tumor histology, nodal status, tumor grading, and lymphatic invasion. Also the use of hyperthermia did not have a significant influence on therapy results. In contrast to these findings, the simultaneous application of chemotherapy during PDR brachytherapy significantly ( p 5 0.01) improved treatment results. Comparing results of salvage PDR brachytherapy with or without simultaneous chemotherapy, the 5-year local recurrencefree survival rate according KaplaneMeyer was 78.9% vs. 38.5% ( p 5 0.01), respectively (Fig. 3). Simultaneous chemotherapy was the only factor shown to have an

Fig. 1. Cumulative incidence of the risk of local recurrence for all patients.

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observed radiation-induced bone necrosis, but also here in only one of these patients (1/51, 2.0%) was surgical treatment necessary. Furthermore, we analyzed the influence that additional hyperthermia and simultaneous chemotherapy had on side effects (Table 2). Here, we found that the simultaneous administration of chemotherapy with brachytherapy seems to be associated with a significant increase in soft-tissue necrosis ( p 5 0.009). All patients scheduled for simultaneous chemotherapy received the intended dose of chemotherapy. Generally, simultaneous chemotherapy was well tolerated. We registered usually only transient mild side effects, bone marrow suppression manifested as leucopenia, anemia, and thrombocytopenia. We observed no Grade 3 or 4 acute side effects.

Discussion Fig. 2. Local recurrence-free survival rates for all patients.

influence on the local recurrence rates achieved by salvage brachytherapy as was confirmed also using multivariate Cox proportional hazards regression analysis ( p 5 0.015). Toxicity During the first weeks of followup after brachytherapy, we observed only mild acute toxicitiesdmostly mucositis Grade 1e2 in 46/52 (90%) of patients. Only five (10%) patients developed mucositis Grade 3. Regarding serious late side effects, 9/51 (17.7%) of the patients developed softtissue necrosis, but only one of these patients (1/51, 2.0%) developed soft-tissue ulceration needing surgical treatment. Furthermore, in 6/51 (11.8%) of patients, we

Fig. 3. Local recurrence-free survival rates for patients with or without simultaneous chemotherapy ( p 5 0.01).

Most patients with persistent or recurrent head and neck cancer succumb to their disease. Salvage surgery is the standard of care as potentially curative treatment with a high risk of local failure of about 59% (23). In a small randomized trial comparing salvage surgery with postoperative re-irradiation and simultaneous chemotherapy to salvage surgery and observation the authors reported increased disease-free survival and better local control using re-irradiation (24). Some authors also use perioperative brachytherapy as a supplementary method immediately after salvage surgery with promising results (25). There is no doubt that salvage surgery and perioperative brachytherapy are feasible but their toxicity is high. Unfortunately, the situation is more difficult in patients where salvage surgery is not possible because when using radiation therapy for macroscopic tumor substantially, higher radiation doses are necessary as compared with radiation therapy after salvage surgery with clear resection margins. It is a well-known fact that radiation therapy with a total dose of 60 Gy or more for head and neck cancer in previously irradiated areas is a difficult treatment associated with a significant risk of serious acute and late side effects (2, 3, 14, 26e28). Although salvage external beam radiation therapy is technically possible, it is rarely attempted with curative intent because of the high risk of complications and unconvincing results (5e9, 29e33) (Table 3). Be that as it may, the fact remains that total dose is a crucial determinant of local control probability of tumor recurrences independent of tumor location (7, 34e39). In a recent study, Rwigema et al. (37) using stereotactic techniques for re-irradiation of recurrent head and neck cancer demonstrated that the higher the total dose the better the local control probability that will result. Unfortunately, according to our knowledge, no dose escalation study addressing the issue of salvage brachytherapy of recurrent head and neck cancer has been published up to now. As far as our experience goes, treatment with doses in the range of 55e60 Gy for re-irradiation of head and neck

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Table 2 Distribution of serious late side effects as a function of additional simultaneous chemotherapy or hyperthermia Therapy modality

Late toxicity Bone necrosis (n) Conservative treatment Surgical treatment Total p Soft-tissue necrosis (n) Conservative treatment Surgical treatment Total p

Brachytherapy þ simultaneous chemotherapy, n 5 35

Brachytherapy without simultaneous chemotherapy, n 5 16

4 0 4 n.s.

1 1 2

2 0 2 n.s.

3 1 4

8 1 9 0.009

0 0 0

4 1 5 n.s.

4 0 4

Brachytherapy þ interstitial hyperthermia, n 5 17

Brachytherapy without interstitial hyperthermia, n 5 34

n.s. 5 not significant.

areas compromised by previous irradiation up to doses of 60e70 Gy represents very narrow tightrope walk between realistic tumor control probability and an unacceptable incidence of serious side effects. Consequently, it comes as no surprise that radiation oncologists tend to be extremely cautious with dosing decisions, and therefore, the majority of these patients are treated with palliative or supportive care only. However, a reasonable number of these patients, if selected carefully, may have a chance for long-term disease control. By virtue of its strictly focal application of radiation dose and its very steep dose dropoff in the neighborhood, brachytherapy offers the possibility in selected patients of re-irradiation of the tumor area with high doses (O60 Gy) and while at the same time effectively limiting doses in the surrounding healthy tissues to very low levels. The observed local control rates of salvage brachytherapy for previously irradiated recurrent head and neck cancer vary very widely (Table 3)dbetween 16% and 86% after 2 to 5 years (7, 16, 40e49). Recently, some authors reported that the use of iodine-125 brachytherapy can be an efficient brachytherapy technique with low morbidity (50e52). Furthermore, interstitial brachytherapy can play an important role in the treatment of lymph node recurrences of head and neck cancer. Using image-guided interstitial high-dose-rate (HDR) brachytherapy for reirradiation of recurrent lymph node metastases of head and neck cancer, local control probabilities on the order of approximately 60e70% have been published (53). In the overall context, it is particularly Mazeron, Peiffert, Pommier, and Narayana (18, 54e56), who have reported very good local control rates up to 80%. Mazeron et al. (56) treated 70 patients with brachytherapy in previously irradiated areas. Local control was achieved in 72% of patients at 2 years. Peiffert et al. (55) performed salvage brachytherapy in 73 patients presenting velotonsillar carcinoma in a previously irradiated field. The 5-year actuarial local control for T1 N0 and T2 N0 was 80% and 67%, respectively. Grade 2 complications occurred in 13% of patients. No Grade 3 or 4 complications were reported.

Narayana et al. (18) in 30 patient reported 2-year local control rates between 40% and 88% and 13% of Grade 3e4 toxicities. Pommier et al. (54) also reached similarly good results in a small patient group without serious late side effects. How rare such good results are in particular concerning side effects becomes obvious when we compare the aforementioned results with the results published by other groups (1, 2, 57e60) (Table 3). Puthawala et al. (45) report data from 220 patients where moderate or severe complications were seen in 27% of the patients. In the analysis of Levendag et al. (17), 20/73 patients (28%) suffered severe side effects. Mazeron et al. (56) observed mucosal ulceration or necrosis in 27% patients. Bartochowska et al. (3) reported an overall complication rate of 35%. Other authors reported severe side effects even in up to 50e60% (1, 2, 57, 59), among them a necrosis rate of up to 14e15% (61) and side effects Grade 4 in up to 7% (57). It is an important fact that serious late side effects appear more often after HDR-salvage brachytherapy than after PDR-salvage brachytherapy (3, 14, 17, 62e65). Comparing these series with our results regarding the effectiveness (5-year local control rate about 60%), and the side effects rate (soft-tissue necrosis 2e18% and bone necrosis 2e12%), the presented results are quite comparable with the best results published to date (54, 62). We assume that three features have had an important influence on our results: first the use of PDR brachytherapy, a therapy method that combines the biologic advantages of lowdose-rate brachytherapy with the technical advantages of the HDR method, second our meticulous attention to quality assurance (14, 20, 66, 67), and third the use of simultaneous chemotherapy. It is obvious that we can only speculate if it was the PDR brachytherapy itself that ensured low toxicity in our analysis. In our view, without consequent quality assurance including image-guided brachytherapy techniques, a low incidence of serious side effects cannot be expecteddit is only with the radiooncologist’s achieving absolute mastery of the sophisticated

Author, year Mazeron et al., 1987 (56) Levendag et al., 1992 (17)

Number of patients

Gandia et al., 1993 (5, 46)

70 55 18 33

Wang et al., 1993 (46) Stevens et al., 1994 (7)

20 85

Peiffert et al., 1994 (55) Cornes et al., 1996 (1) Benchalal et al., 1997 (40)

73 39 14 14 38 169

Krull et al., 1999 (43)

19

Nag et al., 1999 (44) Leung et al., 2000 (72)

7 91

Puthawala et al., 2001 (45)

220

14

Fischer et al., 2002 (16) Spencer et al., 2003 (9)

13 52

Skowronek et al., 2004 (28)

47

Kramer et al., 2005 (10)

38

Hepel et al., 2005 (71)

30

Martinez-Monge et al., 2006 (25)

25

Narayana et al., 2007 (18)

30

Langer et al., 2007 (12)

105

Grimard et al., 2009 (47)

12

Tselis et al., 2011 (53)

74

OS

Oropharynx Oral cavity Oropharynx Miscellaneous head and neck regions Larynx Miscellaneous head and neck regions Oropharynx Neck nodes Miscellaneous head and neck regions Posterior pharyngeal wall Oral cavity, oropharynx Miscellaneous head and neck regions Miscellaneous head and neck regions Base of skull Nasopharynx

Ir-192 LDR-BT EBRT EBRT þ Ir-192 LDR-BT EBRT þ sim. Chemo

72%/5 y 29%/5 y 50%/5 y 36%þ

14%/5 20%/5 20%/5 11 mo

EBRT EBRT Ir-192 LDR-BT Ir-192 LDR-BT Ir-192 LDR-BT EBRT

60%/5 y 27%/5 y

93%/5 y 17%/5 y

36% Grade 3 3% Grade 4 100% Increase of fibroses 8.2% Grade 3 and 4

80e67%/5 y 63%/1 y 43%/3 y

30% na 35%/3 y

0% Grade 3/4 12% Grade 3 64%/Grade 2e3

Ir-192 LDR-BT Ir-192 HDR-BT EBRT  sim. Chemo

61%/5 y 59%/1 y 37%/0.5 y

21%/5 y 49%/1 y 9%/5 y

Ir-192 HDR-BT

34%/2 y

35%/2 y

na na 8e30% Grade 3 and 4 2.5% Lethal side effects na

Ir-192 HDR-BT EBRT Ir-192 HDR-BT Ir-192 LDR-BT

57%/5 y 38%/5 y

29%/5 y 30%/5 y

29% Grade 3/4 73% Grade 3/4

51%/5 y

20%/5 y

27% Grade 3e4

EBRT þ sim. Chemo

na

EBRT

43%/3 y

42%/1 y 8 mo (Median survival) 35%/3 y

45%/Grade 3/4 7.4% Lethal side effects 14% Grade 3

Ir-192 HDR-BT EBRT þ sim. Chemo

na 30%/1 y

46%/5 y 39%/1 y

na na

Ir-192 HDR-BT and PDR-BT

15%/0.5 y

na

75% Grade 3

EBRT þ sim. Chemo

33%/1 y

35%/2 y

34% Grade 3/4

Ir-192 HDR-BT

69%/1 y

37%/2 y

16% Grade 3/4

Ir-192 HDR-BT

86%/4 y

46%/4 y

40% Grade 3/4

Ir-192 HDR-BT

71%/2 y

63%/2 y

13% Grade 3

EBRT þ sim. Chemo

16%/2 y

26%/2 y

Ir-192 LDR-BT

41%/1 y

21%/5 y

28% Grade 3 8% Lethal side effects 25% Grade 3/4

Ir-192 HDR-BT

67%/3 y

6%/3 y

13% Grade 3/4

Miscellaneous head and neck regions Miscellaneous head and neck regions Miscellaneous head and neck regions Nasopharynx Miscellaneous head and neck regions Miscellaneous head and neck regions Miscellaneous head and neck regions Miscellaneous head and neck regions Miscellaneous head and neck regions Miscellaneous head and neck regions Miscellaneous head and neck regions Miscellaneous head and neck regions Neck nodes

Serious late side effects y y y (Median survival)

27% Grade 3 28% Grade 3

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Benchalal et al., 2002 (40)

Local control

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Therapy

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Spencer et al., 2001 (8)

Tumor site

V. Strnad et al. / Brachytherapy

Pommier et al., 1997 (54) Friedrich et al., 1997 (4) De Crevoisier et al., 1998 (6)

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Table 3 Overview of selected results of salvage brachytherapy and external beam radiation as re-irradiation for recurrent head and neck tumors

51 Present analysis, 2013

156

17 Meng et al., 2012 (50)

Bartochowska et al., 2012 (3)

70 15 Qiu et al., 2012 (33) Zygogianni et al., 2012 (32)

Ir 5 iridium; LDR 5 low-dose-rate; BT 5 brachytherapy; EBRT 5 external beam radiation therapy; sim. Chemo 5 simultaneous chemotherapy; na 5 not available; HDR 5 high-dose-rate; PDR 5 pulsed-dose-rate; IMRT 5 intensity modulated radiation therapy; I 5 iodine; OS 5 overall survival.

2e18% Grade 3/4 26%/5 y 57%/5 y (all patients) 39%/5 y (sim. Chemo) 79%/5 y (þsim. Chemo) Ir-192 PDR-BT  sim. Chemo

15% Grade 3 17%/2 y 19.6%/0.5 y Ir-192 HDR-BT and PDR-BT

I-125 LDR-BT

50%/2 y

na

67%/2 y 35 mo (Median survival) 38%/2 y 65%/2 y 80%/3 y EBRT (IMRT) EBRT (IMRT)

29 Jiang et al., 2012 (52)

Miscellaneous head and neck regions Nasopharynx Miscellaneous head and neck regions Miscellaneous head and neck regions Miscellaneous head and neck regions Oral cavity, oropharynx

I-125 LDR-BT

14% Grade 3 27%/3 y 17%/3 y

16e24% Grade 3/4 46% Grade 3

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techniques of image-guided brachytherapy with the ability to analyze and interpret the significance of the distribution and size of dose inhomogeneities not only inside the tumor but particularly in surrounding structures, that it is possible to capitalize on all the aforementioned advantages of PDR brachytherapy. Our experiences with PDR brachytherapy in head and neck tumors that have not been previously irradiated as well as with other tumors point in the same direction (67e70). Whether the use of hyperthermia can also significantly improve the efficacy of salvage interstitial brachytherapy is not clear. Only very scant data are available in the literature relating to the combination of brachytherapy with chemotherapy and interstitial hyperthermia (3, 43, 57, 71e73)din all these analyses, unfortunately no significant improvement of the results of salvage brachytherapy has been found. In our analysis, we found also no influence of the addition of interstitial hyperthermia to salvage brachytherapy on our treatment results, but it is obvious that the addition of simultaneous chemotherapy significantly improved our results.

Conclusions PDR-interstitial brachytherapy with pulse doses between 0.4 and 0.7 Gy/h/24 h with simultaneous chemotherapy is an effective and safe option for curative therapy in selected patients with head and neck cancer in previously irradiated areas, which are not suitable for salvage surgery. References [1] Cornes PG, Cox HJ, Rhys-Evans PR, et al. Salvage treatment for inoperable neck nodes in head and neck cancer using combined iridium 192 brachytherapy and surgical reconstruction. Br J Surg 1996;83:1620e1622. [2] Righi PD, Weisberger EC, Krakovits PR, et al. Wound complications associated with brachytherapy for primary or salvage treatment of head and neck cancer. Laryngoscope 1997;107:1464e1468. [3] Bartochowska A, Wierbicka M, Skowronek J. High-dose-rate and pulsed-dose-rate brachytherapy in palliative treatment of head and neck cancers. Brachytherapy 2012;11:137e143. [4] Friedrich RE, Krull A, Schwarz R, et al. Salvage therapy of advanced squamous cell carcinoma of the mouth cavity and oropharynx. Results of interstitial high-dose-rate brachytherapy combined with ablative tumor surgery. Strahlenther Onkol 1997; 173:507e512. [5] Gandia D, Wilbaultz P, Guillot T, et al. Simultaneous chemoradiotherapy as salvage treatment in locoregional recurrences of squamous head and neck cancers. Head Neck 1993;15:8e15. [6] De Crevoisier R, Bourhis J, Domenge C, et al. Full dose reirradiation for unresectable head and neck carcinoma: Experience at the Gustave-Roussy institute in a series of 169 patients. J Clin Oncol 1998;16:3556e3562. [7] Stevens KRJ, Britsch A, Moss WT. High-dose reirradiation of head and neck cancer with curative intent. Int J Radiat Oncol Biol Phys 1994;29:687e698. [8] Spencer SA, Harris J, Wheeler RH, et al. RTOG 96-10: Reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2001;51:1299e1304.

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