Improved survival in patients with FDG-PET/CT-based radiotherapy treatment planning for squamous cell anal cancer.

The aim of this retrospective analysis was to evaluate the impact of FDG-PET/CT-based target volume definition on locoregional control and survival, compared to conventional CT-based target volume definition and dose prescription. One hundred and twenty-two patients with squamous cell anal cancer were treated with curative radiotherapy (RT) alone (27%) or with RT with concurrent chemotherapy (73%) and analyzed. Forty-six percent had the early disease (stage I+II) and 54% were stage III. FDG-PET/CT-based staging was performed in 21% of the patients. The mean follow-up time was 60 months. Other risk factors affecting survival were investigated. According to initial staging in both groups (FDG-PET/CT and conventional CT) were 10% of stage IV disease, and they were excluded from radical radiotherapy and treated with palliative intent. Ninety-two percent of the patients achieved complete remission. Significant favorable factors in univariate analysis associated with disease-free survival (DFS) were PET/CT staging, T1/2 and N0 stage, and clinical stage I and II. Locoregional control (LRC) correlated with the T1/2 stage and initial performance status (PS) 0. There were no significant factors affecting overall survival (neither in univariate nor multivariate analysis). In multivariate analysis, the factor associated with better DFS was PET/CT staging and for LRC, PS 0 and concomitant chemoradiation. Acute toxicity was increased in the concurrent chemo-radiotherapy group. Two-, five- and ten-year overall survival rates were 83%, 69%, and 60%; disease-free survival rates were 76%, 73%, 73%; local control rates were 91%, 90%, and 90% and colostomy-free survival was 89%, 86%, and 81%, respectively. PET/CT staging allowed targeted dose escalation to the primary tumor and nodal metastases while decreasing dose to uninvolved regions, resulting in significantly improved DFS without compromising locoregional control.

Radiotherapy and radiosensitivity syndromes in DNA repair gene mutations.

BACKGROUND: Ionizing radiation DNA damage is the main mechanism of radiotherapy (RT) action and the outcome of treatment and healthy tissue toxicity is influenced by a number of external and internal factors, including mutations in DNA damage recognition and repair. Disorders of DNA repair may result in increased sensitivity to cancer treatment. PURPOSE: The mechanism of DNA repair and an overview of genetic syndromes with mutations in genes involved in DNA repair clarify the accelerated carcinogenesis and increased radiosensitivity in RT cancers. Most radiosensitivity syndromes are autosomal recessively inherited; examples are ataxia teleangiectasia, Nijmegen breakage syndrome, xeroderma pigmentosum, Cockayne syndrome, Bloom syndrome and Werner syndrome. CONCLUSION: Radiotherapy is contraindicated in most homozygous patients with recessive radiosensitivity syndromes. Asymptomatic heterozygotes may have an increased risk of tumor incidence and a small part of them slightly increased risk of RT intolerance; however, this does not limit RT treatment. The high risk of secondary malignancies after radiotherapy is a contraindication to adjuvant RT in Li-Fraumeni syndrome.

Haematotoxicity in IMRT/VMAT curatively treated anal cancer.

INTRODUCTION: Curative chemoradiotherapy of squamous cell carcinoma achieves long-term complete remissions in most patients and minimizing treatment toxicity becomes crucial issue. The aim of the retrospective analysis was to determine an acceptable dose to the bone marrow for radiotherapy planning not leading to increased haematological toxicity. PATIENTS AND METHODS: In the period 2013-2019, 40 patients with squamous cell carcinoma were curatively treated at the Department of Oncology of the University Hospital Motol using intensity modulated radiotherapy (IMRT) /volumetric modulated arc radiotherapy (VMAT) technique. Women make up 90% of the group, the average age at the time of dia-gnosis was 65 years (47-81). Chemotherapy mitomycin C and 5-fluorouracil was given to 68% of patients. The bone marrow was contoured in the Varian Eclipse planning system, version 15.6. RESULTS: Acute hematotoxicity (G3, 4, 5 according to Common Terminology Criteria for Adverse Events - CTCAE) was significantly associated with the concomitant chemoradiotherapy (P = 0.002) and the average dose to the bone marrow 27 Gy (P = 0.011). Late haematological toxicity was mild (maximum grade 1), asymptomatic, and no dependence of late haematotoxicity on any risk factor (age, gender, WHO performance status, bone marrow dose, CHT, BMI, smoking, stage) was proved. The overall survival at 5 years was 100% in stage I, 83% in stage II, 61% in stage III and 0% in stage IV. Local control at 5 years is 100% in stage I, 92% in stage II, 87% in stage III and 0% in stage IV. Local recurrence developed in 5% of radically treated patients. Distant metastases occurred in 8% of radically treated patients. Local recurrences or metastases occurred only during the first 2 years after the treatment. CONCLUSION: Radical chemoradiotherapy in the treatment of squamous cell anal carcinoma is highly effective. IMRT/VMAT enabled to apply a sufficiently effective dose to the tumor and elective areas and reduced not only acute skin, GI and GU toxicity, but also acute haematological toxicity in cases with the dose Dmean to bone marrow lower than 27 Gy. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical, papers.