Radical interstitial HDR brachytherapy in treatment of recurrent vulvar cancer: a case study

Introduction

Vulvar cancer is one of the rarest gynaecological cancers [1, 2], but for last decades the number of new cases has increased, especially among young patients [1, 3, 4]. It accounts for 2-5% of all gynaecological carcinomas and about 0.6% of all malignant neoplasms in women [1, 5, 6]. Nowadays about 30% of patients who report with the advanced disease [5] are unable to undergo the standard treatment which is radical vulvectomy with inguinal lymph node dissection.

Recurrences in vulvar cancer are serious problems. Local failures are the most frequent while and groin recurrences are less common [6]. It is estimated that even in multimodality treatment, about 10-20% of patients with FIGO I and 50-70% with the advanced disease will recur [5, 7–9] and 40% of them will die [5]. Local failures may be successfully treated with surgery or radiotherapy, while patients with groin recurrences usually die [6, 10].

In the past, radiotherapy of vulvar cancers was less popular, e.g. because of frequent skin necrosis that limited the use of both external beam radiotherapy (EBRT) and brachytherapy. The orthovoltage X-rays gave a very high dose to skin, which is thin, delicate and highly vascularised in that region, causing troublesome and painful reactions [11]. Also brachytherapy was recommended as a method which should be used sparingly because of high morbidity in spite of its high effectiveness [12]. There is still an opinion that vulva is not a tissue that tolerates interstitial implants very well and tumours localized in that area are often not amenable to template guided implants [11].

In the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch inter­stitial HDR brachytherapy has been performed in selected patients with primary or recurrent vulvar can­cer for twenty years. In patients who are not eligible for radical surgery or with the advanced or recurrent disease, that method is a proper treatment option offering good local control [13-15]. Nowadays, modern external beam radiotherapy and brachytherapy with advanced equipment and precise treatment planning, offers a highly conformal technique with a lower number of complications. Interstitial HDR brachytherapy delivers a high dose of radiation strictly to the tumour while sparing the adjacent healthy tissues. Due to the sensitive nature of the vulvar tissues, interstitial brachytherapy offers an effective, gentle and individualized therapy in a short time [9].

Case report

A 90-year-old woman with locally recurrent vulvar cancer was treated in the Maria Sklodowska-Curie Me­morial Cancer Center and Institute of Oncology Gliwice Branch in 2005 and 2010 using interstitial HDR brachytherapy.

In 2000, at the age of 80, she was diagnosed with a vulvar well differentiated squamous cell carcinoma with keratinization (G-1). Exophytic 2.5 cm tumour was localized on thr left large pudendal labia. Inguinal lymph nodes were not palpable, no other pathological changes were found. The patient was referred to a simple vulvectomy. The tumour was removed with some safety margins. After three months, an enlargement of left inguinal lymph nodes was observed. The left inguinal lymph node biopsy showed squamous cell carcinoma and inguinal lymphadenectomy was performed.

The patient attended follow-up visits only for two years.

In 2005, on the left side of the vulvar scar, a 2-cm recurrent tumour was noticed. No other pathological changes were found. The patient was referred to radical interstitial HDR brachytherapy.

In local anaesthesia three catheters were inserted into the tumour with a healthy tissue margin. The first session started on the same day after catheters’ insertion.

The clinical target volume was determined either by clinical examination or CT imaging. The dose of interstitial HDR brachytherapy was prescribed 5 mm from the surface of applicator. Computerized optimization and three dimensional dose distribution were obtained using the PLATO System. HDR brachytherapy was performed with afterloading Ir192 source using microSelectron HDR (Nucletron). The total dose was 32Gy delivered twice a day with a 6 hours’ break in fractionation dose 3.2Gy (Table I).

Just after the last fraction on the 5th day (ten frac­tions), all catheters were removed. The healing process proceeded without any complications showing good tolerance of therapy.

Five weeks after the therapy the patient complained about itching and burning in the uro-genital area. In

the tumour bed a 2 cm focus of epitheliolysis was noticed which healed in sequential follow-up visits.

Since 2008, the patient has stopped attending follow-up visits.

In February 2010, on the right side of a scar after vulvectomy, a local recurrence was noticed. The patient complained about an increasing discomfort and pain in vulva and perineum. On vulva there were two tumours: one on the right side of a scar after vulvectomy and the second in the area of posterior commissure of 2 cm and 0.5 cm in diameter, respectively. On the left side, in the area after previous brachytherapy, only a smooth scar with no evidence of recurrence was observed.

The patient was referred to the second radical interstitial HDR brachytherapy. In local anaesthesia three catheters (type: Comfort) were inserted into tumours with a safety margin. Fig. 1. The interstitial HDR brachytherapy schedule was the same as before (Fig. 2). The total dose was 31.5Gy delivered twice a day with a 6 hours’ break in fractionation dose 3.5Gy (nine fractions) (Table I).

After five days the catheters were removed. The heal-

ing process proceeded without any complications showing good tolerance of therapy. Only during the first days of therapy and about two weeks after the catheter removal, the patient reported itching and slight pain. There were visible superficial epitheliolysis and fibrin coat in examination in the treated area.

At present the patient is attending periodical follow-up visits. The inguinal lymph nodes were not oncologically suspicious in the ultrasound examination. In histopathology taken from the treated area there was only hyperplasia acanthotica with inflammatory cells.

Discussion

In recurrent vulvar cancer there is no standard treat­ment. A relatively low number of primary vulvar cancers with a low proportion of recurrences is the reason why it is difficult to perform randomized studies to document the most appropriate therapeutic modalities. In local failures, surgery or radiotherapy may be performed.

Radiotherapeutic management of recurrent vulvar cancer may incorporate interstitial brachytherapy as a part of the treatment, especially among patients disqualified from radical surgery [11, 16]. Vulvar cancers, similarly to other squamous cell cancers, are very sen­sitive to radiation [10], but on the other hand, the vulvar skin tolerates radiotherapy poorly and toxicity limits its use [13, 17].

There are only few reports in the literature concerning recurrent vulvar cancer treated with interstitial HDR brachytherapy [9, 18, 19]. It may be used as a “boost” or as a sole treatment.

It is well documented that interstitial brachytherapy makes it possible to achieve a very good local control [9, 13, 15, 16, 18, 19]. Jolicoeur described patients with early vulvar cancer (Tis, T1N0M0) and recurrent carcinoma (in situ) who were treated with interstitial HDR brachy­therapy. The treatment scheme was similar to ours as regards the total doses (36 Gy) and the number of fractions (12). He obtained good results with a median follow-up of 30 months with disease-free survival and a survival rate of 98% and 100%, respectively [18]. Frezza also analyzed a group of patients with primary or recurrent vulvar cancer treated with brachytherapy. That group of patients was not eligble for a radical surgery and they were referred to adjuvant brachytherapy with or without EBRT. He reported brachytherapy alone or in combination with EBRT as a valid modality of therapy for selected patients not eligible for surgery [19].

Our patient has undergone radical interstitial HDR brachytherapy twice because of two local recurrences on vulva. The interstitial HDR Brachytherapy technique allowed us to use that method twice in one patient in areas which were localized on vulva very close to each other. After the first therapy we achieved a very good local control. The second failure occurred five years later on the opposite side of the vulva. In the last histopathology there were no tumour cells. The patient is under control but there are no symptoms of an active disease.

In our study interstitial HDR brachytherapy was tolerated very well; our patient had only acute com­plications. Other authors also observed a low number of complications [9, 14, 18]. Jolicoeur observed acute toxicity grade 2 in all patients but late severe toxicity only in two women [18].

In the literature, there is information that interstitial brachytherapy may cause severe toxicity [11, 12, 15] and in our practice we also observed some severe treat­ment complications. A very important issue is a proper qualification to therapy, fractionation scheme and total dose to the tumour. We have our own scheme of fractionation and the dose per session is usually 3,5 Gy in the case of a vulvar cancer. In our opinion it is not only safe, but also effective. In the past, when the doses were a bit higher, we observed more complications. The total doses in the vulvar region depend on the treatment aim, but in radical therapy it is about 32 Gy.

Due to the anatomy of perineum, the close urethra and anus there are crucial issues in treatment planning especially in recurrent vulvar cancer. Brachytherapy delivers a high dose of radiation strictly to the tumour while sparing the adjacent healthy tissues, because of rapid fall in dose outside the target. It brings about good cosmetic results with functional and anatomical organ preservation [13, 14], which is especially important among young women with vulvar cancer who suffer from severe psychological stress caused by hugely deforming surgery. It is estimated that about 15% of all vulvar cancers occur among young women [20] and

the number is increasing [1, 3, 4, 21].

Recurrent disease is most frequently localized near the site of the primary lesion [17]. According to the li-

terature, a recurrent vulvar cancer after radical surgery procedures occurs in 15-40% [6-8, 22, 23] of patients and more than 50% are localized in the vulvar area [6, 22]. In our patient both recurrences occurred on vulva, close to vulvectomy scar.

Failures usually occur during the first two years after initial surgical management [7, 17], but in some cases they may appear even five years or more after the primary treatment [7]. Sometimes three or more local recurrences are observed [6]. Some authors suggest that late failures may be a recurrent disease but also a second primary tumour and they often occur among patients with previously diagnosed vulvar lichen sclerosus [6]. Our patient had the first recurrence 5 years after the surgery and the second – 10 years after the previous treatment, both in different areas of vulva. Nicoletto et al. had 46% of the second local recurrences in his study [24], and Wooderlink et al. observed a second or further local failure in 72% of patients [6]. Our patient did not suffer from lichen sclerosus vulvae.

It is estimated that histological excision margin smaller than 8 mm is associated with a 50% rate of a local recurrence while a histological margin of 10 mm or greater is connected with a very low risk of failure [17]. In our study there was no pathology revision and therefore histological margins were not analyzed.

In our opinion, interstitial HDR brachytherapy among selected patients with a local recurrence of vulvar cancer is an effective and safe method which allows to preserve organ functions while providing good cosmetic results.

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