Comparison of cisplatin and mitomycin C/5-FU as radiosensitisers in the treatment of locally advanced vulvar cancer: results of a retrospective, observational, single-institutional cohort study.

PURPOSE: We retrospectively investigated the widely used radiosensitisers cisplatin and mitomycin C/5-fluorouracil (5-FU) in patients with locally advanced vulvar cancer for outcome and toxicity. METHODS: We screened the archive for patients treated with chemoradiation for vulvar cancer diagnosed between 01/2010 and 08/2021 at our institution. The impact of both radiosensitisers on prognosis was compared using Kaplan-Meier method and Cox-regression analysis. RESULTS: One hundred and forty-three patients with vulvar cancer were screened. Twenty-nine patients received chemoradiation (mitomycin C/5-FU n = 14; cisplatin n = 12; others n = 3) as a primary, neoadjuvant or adjuvant treatment. Median follow-up was 15.5 months. Patients in the cisplatin group were older (mean age 54.4 vs. 70.7; p = 0.004). However, the mitomycin C/5-FU group had more advanced tumour stages. The 2-year recurrence-free survival (RFS) was comparable (44.5% vs. 33.3%; p = 0.932). The 2-year overall survival (OS) showed a numerical but not statistically significant difference in favour of the mitomycin C/5-FU group (59.7% vs. 31.7%; p = 0.37). 64.3% (9 out of 14) patients, who received mitomycin C/5-FU achieved clinical complete response (cCR) compared to 41.7% (5 out of 12) who received cisplatin (p = 0.505). Radiodermatitis was the most common adverse event in both groups (81%) and more severe in the mitomycin C/5-FU cohort. Myelotoxicity was frequently observed in both groups. Eighteen patients received an additional radiation boost with 10.0 (9-16) Gy and showed a significantly prolonged RFS (p = 0.027) and OS (p = 0.003). CONCLUSION: Mitomycin C/5-FU may be considered in the treatment of young and healthy patients with locally advanced vulvar cancer.

Radiation-induced DNA double-strand breaks in peripheral leukocytes and therapeutic response of heel spur patients treated by orthovoltage X-rays or a linear accelerator.

PURPOSE: Biodosimetric assessment and comparison of radiation-induced deoxyribonucleic acid (DNA) double-strand breaks (DSBs) by γH2AX immunostaining in peripheral leukocytes of patients with painful heel spur after radiation therapy (RT) with orthovoltage X­rays or a 6-MV linear accelerator (linac). The treatment response for each RT technique was monitored as a secondary endpoint. PATIENTS AND METHODS: 22 patients were treated either with 140-kV orthovoltage X­rays (n = 11) or a 6-MV linac (n = 11) with two weekly fractions of 0.5 Gy for 3 weeks. In both scenarios, the dose was prescribed to the International Commission on Radiation Units and Measurements (ICRU) dose reference point. Blood samples were obtained before and 30 min after the first RT session. γH2AX foci were quantified by immunofluorescence microscopy to assess the yield of DSBs at the basal level and after radiation exposure ex vivo or in vivo. The treatment response was assessed before and 3 months after RT using a five-level functional calcaneodynia score. RESULTS: RT for painful heel spurs induced a very mild but significant increase of γH2AX foci in patients' leukocytes. No difference between the RT techniques was observed. High and comparable therapeutic responses were documented for both treatment modalities. This trial was terminated preliminarily after an interim analysis (22 patients randomized). CONCLUSION: Low-dose RT for painful heel spurs with orthovoltage X­rays or a 6-MV linac is an effective treatment option associated with a very low and comparable radiation burden to the patient, as confirmed by biodosimetric measurements.

Adjuvant temozolomide-based chemoradiotherapy versus radiotherapy alone in patients with WHO III astrocytoma: The Mainz experience.

BACKGROUND: It is currently unclear whether adjuvant therapy for WHO grade III anaplastic astrocytomas (AA) should be carried out as combined chemoradiotherapy with temozolomide (TMZ)--analogous to the approach for glioblastoma multiforme--or as radiotherapy (RT) alone. PATIENTS AND METHODS: A retrospective analysis of data from 90 patients with AA, who were treated between November 1997 and February 2014. Assessment of overall (OS) and progression-free survival (PFS) was performed according to treatment categories: (1) 50%, RT + TMZ according to protocol, (2) 11%, RT + TMZ with dose reduction, (3) 26%, RT alone, and (4) 13%, individualized, primarily palliative therapy. No dose reduction was necessary in the RT alone group. RESULTS: Median OS was 85, 69, and 43 months for treatment categories 1/2, 3, and 4, respectively. These differences were not statistically significant. PFS was 35, 29, 48, and 33 months for categories 1, 2, 3, and 4, respectively; again without significant differences between categories. In a subgroup of 39 patients with known IDH1 R132H status, the presence of this mutation correlated with significantly longer OS (p = 0.01) and PFS (p = 0.002). Complete or partial tumor resection and younger age also correlated with a significantly better prognosis, and this influence persisted in multivariate analysis. In the IDH1 R132H subgroup analysis, only this marker retained an independent prognostic value. DISCUSSION AND CONCLUSION: A general superiority of combined chemoradiotherapy compared to RT alone could not be demonstrated. Biomarkers for predicting the benefits of combination therapy using RT and TMZ are needed for patients with AA.