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1.  Management of patients with vulvar cancer: a perspective review according to tumour stage 
Treatment of patients with vulvar cancer is challenging for gynaecologic oncologists. Owing to the localization in a sensitive area, surgical radicality and the indication for adjuvant treatment have to be balanced with psychosocial aspects to treat patients adequately. Clinical management is therefore highly dependent on the tumour stage. For patients with early-stage disease (FIGO I–II) therapy mainly concentrates on surgery with resection of the primary tumour and staging of the groin lymph nodes. In intermediate-stage vulvar cancer (FIGO III), advanced disease is expressed by affected inguinofemoral lymph nodes bringing radical lymphadenectomy and adjuvant therapy as well as radiation or chemoradiation into the focus of treatment. For locally advanced or metastatic vulvar cancer (FIGO IV) neoadjuvant or definitive chemoradiation has to be considered besides surgery. Owing to the low incidence of the disease, the level of evidence for different treatment modalities is poor. This review therefore puts different recommendations of clinical management in context and highlights the need for future trials.
PMCID: PMC3630479  PMID: 23634196
adjuvant therapy; chemoradiation; locally advanced tumour; radiotherapy; surgery; treatment; vulvar cancer
2.  Late Toxicity of Radiotherapy: A Problem or a Challenge for the Radiation Oncologist? 
Breast Care  2011;6(5):369-374.
Large randomized clinical trials have established radiotherapy in conjunction with adjuvant systemic treatment as standard treatment in breast cancer after both mastectomy and lumpectomy. Although standard radiation therapy is well tolerated by the majority of patients, some patients might suffer from late normal tissue effects.
The literature on radiotherapy following surgery of breast cancer was reviewed with regard to late toxicity.
Radiotherapy may, to some degree, cause persistent pain in the breast, arm and shoulder in up to 30–50% of patients after 3–5 years, lymphedema in 15–25%, and restriction of arm and shoulder movement in 35%. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy may cause damage to the heart. However, using modern radiotherapy techniques, the available evidence does not suggest a higher incidence of cardiac mortality.
This review updates the database on toxicity from radiation in breast cancer. Advances in research of radiation-induced late effects may lead to improved treatment choices for breast cancer patients including radiotherapy and may improve quality of life after surviving breast cancer.
PMCID: PMC3357174  PMID: 22619647
Breast cancer; Late effects; Radiotherapy
3.  Association of single nucleotide polymorphisms in the genes ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with risk of severe erythema after breast conserving radiotherapy 
To examine the association of polymorphisms in ATM (codon 158), GSTP1 (codon 105), SOD2 (codon 16), TGFB1 (position −509), XPD (codon 751), and XRCC1 (codon 399) with the risk of severe erythema after breast conserving radiotherapy.
Methods and materials
Retrospective analysis of 83 breast cancer patients treated with breast conserving radiotherapy. A total dose of 50.4 Gy was administered, applying 1.8 Gy/fraction within 42 days. Erythema was evaluated according to the Radiation Therapy Oncology Group (RTOG) score. DNA was extracted from blood samples and polymorphisms were determined using either the Polymerase Chain Reaction based Restriction-Fragment-Length-Polymorphism (PCR-RFL) technique or Matrix-Assisted-Laser-Desorption/Ionization –Time-Of-Flight-Mass-Spectrometry (MALDI-TOF). Relative excess heterozygosity (REH) was investigated to check compatibility of genotype frequencies with Hardy-Weinberg equilibrium (HWE). In addition, p-values from the standard exact HWE lack of fit test were calculated using 100,000 permutations. HWE analyses were performed using R.
Fifty-six percent (46/83) of all patients developed erythema of grade 2 or 3, with this risk being higher for patients with large breast volume (odds ratio, OR = 2.55, 95% confidence interval, CI: 1.03–6.31, p = 0.041). No significant association between SNPs and risk of erythema was found when all patients were considered. However, in patients with small breast volume the TGFB1 SNP was associated with erythema (p = 0.028), whereas the SNP in XPD showed an association in patients with large breast volume (p = 0.046). A risk score based on all risk alleles was neither significant in all patients nor in patients with small or large breast volume. Risk alleles of most SNPs were different compared to a previously identified risk profile for fibrosis.
The genetic risk profile for erythema appears to be different for patients with small and larger breast volume. This risk profile seems to be specific for erythema as compared to a risk profile for fibrosis.
PMCID: PMC3439287  PMID: 22537351
Single nucleotide polymorphisms (SNPs); Erythema; Breast cancer; Radiotherapy
4.  [18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes 
At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT) and imaged guided radiotherapy (IGRT), it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues.
Twenty-six patients with primary (n = 7) or recurrent (n = 19) prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs). PET/CT-scans with F18-fluoroethylcholine (FEC) were performed on a combined PET/CT-scanner equipped for radiation therapy planning.
The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months.
The mean SUVmax in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUVmax of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2) in 15%. No or mild late side effects were observed in the majority of patients (84%). One patient had a severe bladder shrinkage (grade 4) after a previous treatment with TUR of the prostate and seed implantation.
FEC-PET/CT planning could be helpful in dose escalation to lymph nodal sites of prostate cancer.
PMCID: PMC3095991  PMID: 21529377
5.  Reirradiation of recurrent breast cancer with and without concurrent chemotherapy 
Treatment options for loco-regional recurrent breast cancer after previous irradiation are limited. The efficacy of chemotherapy might be hampered because of impaired tissue perfusion in preirradiated tissue. Thus, mastectomy or local excision and reconstructive surgery are the preferred treatments. However, in recent years evidence accumulates that a second breast conserving approach with reirradiation as part of the treatment might be feasible and safe and, furthermore, reirradiation might be an option for palliation. Here we report on the experience of a single community centre in reirradiation of recurrent breast cancer.
The report is based on 29 patients treated with reirradiation. All data were prospectively collected. The median age was 63 years (range 35 to 82 yrs). The interval between initial diagnosis and diagnosis before start of reirradiation was 11.6 months to 295.5 months. The mean total dose (initial dose and reirradiation dose) was 106.2 Gy (range 80.4 to 126 Gy) and the mean BED3 Gy 168,5 Gy (range 130,6 to 201,6). The mean interval between initial radiotherapy and reirradiation was 92.9 months (range 8.7 to 290.1). Inoperable or incompletely resected patients were offered concurrent chemotherapy with either 5-FU or capecitabine. All patients received 3D-conformal radiotherapy with 1.6 to 2.5 Gy/fraction five times weekly. The treatment volume comprised all visible lesions or lesions detectable on CT/MRI/FDG-PET/CT or the tumour bed or recurrent tumour.
The local progression-free survival of all patients at one and two years was 81% and 63%. Patients who had no surgery of the recurrence (16/29) had local progression-free survival at one and two years of 72% and 25% with a median progression-free survival time of 17 months. Partial remission and good symptom relief was achieved in 56% (9/16) or complete response of symptoms and/or tumour in 44% (7/16). Patients who had no distant metastases and had at least an R1-resection had a local progression-free survival of 90% after 2 years. The disease-free survival after 2 years was 43% and the median disease-free survival time was 24 months. In four patients a second breast conserving operation was performed and the cosmetic results in all four patients are good to excellent. Acute side effects were mild to moderate with no grade 3 or 4 toxicity. Accordingly, no grade 3 or 4 late effects were observed so far. No grade 3 or 4 plexopathy was observed.
In this heterogeneous group of patients reirradiation of locoregional recurrences of breast cancer showed low to moderate acute toxicity. In our experience, local control rates are high and palliation is good.
PMCID: PMC2556652  PMID: 18801165

Results 1-5 (5)