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Purpose: The aims of this study were to investigate the clinical feasibility and to report on preliminary treatment outcomes of combined intracavitary/interstitial brachytherapy, using a novel applicator and magnetic resonance imaging (MRI)–based treatment planning in patients with locally advanced cervical cancer. Methods and Materials: A total of 22 cervical cancer patients with insufficient response and/or unfavorable topography after external-beam irradiation were included in this study. Parametrial extent of the disease in these patients was judged to exceed the coverage limit of intracavitary brachytherapy alone. A modified tandem/ring (T/R) applicator for guidance of parametrial needles (N) was used to perform high-dose-rate-brachytherapy with MRI-based treatment planning. Clinical feasibility and preliminary treatment outcomes were assessed. Results: A total of 44 interstitial needle implants were performed. The spatial relations between the T/R + N applicator, high-risk clinical target volume, and organs at risk were visible clearly in all cases. Accurate and reproducible needle placement could be achieved in the majority of cases. No severe adverse events were caused by the intervention. The mean follow-up period was 20 months (range, 5–35 months). No G3 to G4 early or persistent late side effects were observed. Complete remission was achieved in 21 patients (95%). One local recurrence was observed within the high-risk clinical target volume area during follow-up. Conclusions: Our preliminary clinical experience indicates that combined intracavitary and interstitial MRI-based brachytherapy in patients with significant residual disease after external-beam therapy extending up to the distal third of parametria is feasible and allows excellent local control and a low rate of morbidity. [Copyright &y& Elsevier]

Purpose: To compare magnetic resonance imaging (MRI) findings at different stages of cervix cancer treatment and to define the potential of MRI to delineate the gross tumor volume (GTV), clinical target volume (CTV), pathoanatomic structures, and organs at risk (OAR) in brachytherapy. Methods and Materials: Forty-nine patients underwent MRI at diagnosis and at brachytherapy. The ability to discriminate anatomic structures on MRI was assessed (quality factor: 0 = inability to discriminate; 1 = fair discrimination; 2 = good discrimination; 3 = excellent discrimination). The overall ability to visualize (percentage of patients with quality factors greater than 0) and the overall discrimination quality score (mean quality factors of all patients) were estimated for the applicator, GTV at diagnosis (GTVD), GTV at brachytherapy (GTVBT)/“gray zones,” cervix rim/uterine corpus, OAR, vaginal wall, and parametria. Results: The overall ability to visualize the applicator on MRI at brachytherapy was 100%; for the GTVBT/“gray zones,” cervix rim/uterine corpus, OAR, and vaginal wall, visualization was 98% (overall discrimination quality factors: 1.2, 2.9, 2.1, 1.9, 1.7, and 2.6). Three of 4 borders of parametrial space were defined in more than 98% (discrimination quality factors: 2.9, 2.1, and 1.2). Conclusion: Magnetic resonance imaging provides appropriate information for definition of the applicator, GTV, CTV, pathoanatomic structures, and OAR that enables precise delineation for cervix cancer brachytherapy. [Copyright &y& Elsevier]

Abstract: Background: To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT)±chemotherapy (ChT). Methods: Treatment schedule was EBRT with 45–50.4Gy±concomitant cisplatin chemotherapy plus 4×7Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90>85Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75Gy for rectum and sigmoid and 90Gy for bladder. Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis. Findings: One hundred and fifty-six consecutive patients (median age 58years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42months for all patients. Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93±13Gy, D2cc 86±17Gy for bladder, 65±9Gy for rectum and 64±9Gy for sigmoid. Complete remission was achieved in 151/156 patients (97%). Overall local control at 3years was 95%; 98% for tumours 2–5cm, and 92% for tumours >5cm (p =0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3years was overall 74%, 83% for tumours 2–5cm, 70% for tumours >5cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3years was in total 68%, 72% for tumours 2–5cm, 65% for tumours >5cm, 74% for IB, 78% for IIB, 45% for IIIB. In regard to late morbidity in total 188 grade 1+2 and 11 grade 3+4 late events were observed in 143 patients. G1+2/G3+4 events for bladder were n =32/3, for rectum n =14/5, for bowel (including sigmoid) n =3/0, for vagina n =128/2, respectively. Interpretation: 3D conformal radiotherapy±chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100% at 3years in limited/favourable (IB/IIB) and 85–90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings. [Copyright &y& Elsevier]

Purpose: To investigate dosimetric uncertainties of MRI-based cervix cancer brachytherapy, when applying two HDR fractions for each applicator insertion and their clinical relevance. Methods: 21 patients with 84 MRI-examinations and fractions were investigated. After insertion of the MRI compatible tandem-ring applicator, an MRI-set was recorded and the treatment plan optimised for the first fraction. Prior to the second fraction 16–20h later a second MRI-set was recorded, and the dose distribution from the plan of the previous day superimposed and analysed. The same procedure was repeated for fractions 3 and 4. Dose from EBRT and brachytherapy was normalised to 2Gy-fractionation (EQD2), added up to a total dose, and compared to a calculated total dose if only 1 MRI-examination per insertion is available. Results: The total D90 for High risk (HR) CTV was 1.2±2.7Gyαβ10 (1±3%) (mean±1SD) lower by individual MRI-evaluation of each fraction compared to 1 MRI per insertion. The increased by 0.7±4.7Gyαβ3 (1±6%) for bladder, 1.1±2.4Gyαβ3 (2±4%) for rectum and decreased by 0.8±3.4Gyαβ3 (1±5%) for sigmoid. For HR CTV the individual approach did not identify any case with a decrease of D90 >5Gyαβ10. For the bladder 3 cases, for the rectum no case and for the sigmoid 1 case was identified with an increase of >5Gyαβ3. For the bladder all dose variations of more than 5Gyαβ3 could have been avoided by ensuring a constant bladder filling. Individual MRI-evaluation did not determine any case where dose constraints were not fulfilled. Conclusions: For the treatment schedule as applied in this study, geometric differences between applicator, target and OAR result in overall dosimetric changes, which seem to be of minor relevance in regard to clinical dose volume constraints applied at present. [ABSTRACT FROM AUTHOR]