Local recurrences in cervical cancer patients in the setting of image-guided brachytherapy: A comparison of spatial dose distribution within a matched-pair analysis

AbstractPurposeIt has been shown that a cumulative dose of ⩾87Gy (EQD2) of external beam radiotherapy (EBRT) and image guided adaptive brachytherapy (IGABT) to the high risk clinical target volume (HR CTV) confer a local control rate >95% in locally advanced cervical cancer. This study examines the dose distribution within the HR CTV and intermediate (IR) CTV in patients with cervical cancer treated with definitive EBRT +/− concomitant chemotherapy and MRI-based IGABT between patients with local recurrence (LR) and patients in continuous complete local remission (CCLR).Material and methodsFrom 1998 to 2010, 265 patients were treated with definitive EBRT +/− concomitant chemotherapy and IGABT. Twenty-four LRs were documented. For the statistical analysis all patients with LR were matched to patients in CCLR from our database according to the following criteria: FIGO stage, histology, lymph node status, tumour size and chemotherapy.DVH parameters (D50, D90, D98, D100) were reported for HR CTV and IR CTV. In order to report the minimum dose in the region where the recurrence occurred, the HR CTV/IR CTV were divided into four quadrants on transversal planes. The minimum dose at the HR CTV/IR CTV contour was measured (within the corresponding quadrant closest to the LR) in the treatment planning system. A mean minimum point dose (MPD) was calculated by averaging these measurements on four consecutive slices at the level of the recurrence for each of the 4 brachytherapy fractions. EQD2 doses were calculated by summation of all BT and external beam therapy fractions.For each matched patient in the control group the measurements were performed on the same quadrant and at the same level.ResultsSufficient image data were available for 21 LRs. Eight central failures and 13 non-central failures were observed. The mean D90 and D100 for HR CTV were 77Gy and 61Gy for patients with LR and 95Gy and 71Gy for patients in CCLR, respectively (p<0.01). The MPD for HR CTV was 72Gy for patients in the LR arm and 99Gy for patients in the CCLR arm (p<0.01). In the LR arm seven patients had a D90 for HR CTV ⩾87Gy, however, in only three patients the MPD was ⩾87Gy.ConclusionThis study demonstrated significant differences in local outcome according to the delivered dose. In 85% of the LRs systematic low dose regions with less than 87Gy were found at HR CTV contour. Systematic low dose regions leading to local recurrence could be detected even if a D90 HR CTV ⩾87Gy was applied. In addition to DVH parameters, inspection of the spatial dose distribution remains a key point in dose prescription

Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer

AbstractBackgroundTo 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).MethodsTreatment 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.FindingsOne 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.Interpretation3D 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

Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (IV): Basic principles and parameters for MR imaging within the frame of image based adaptive cervix cancer brachytherapy

The GYN GEC-ESTRO working group issued three parts of recommendations and highlighted the pivotal role of MRI for the successful implementation of 3D image-based cervical cancer brachytherapy (BT). The main advantage of MRI as an imaging modality is its superior soft tissue depiction quality. To exploit the full potential of MRI for the better ability of the radiation oncologist to make the appropriate choice for the BT application technique and to accurately define the target volumes and the organs at risk, certain MR imaging criteria have to be fulfilled. Technical requirements, patient preparation, as well as image acquisition protocols have to be tailored to the needs of 3D image-based BT. The present recommendation is focused on the general principles of MR imaging for 3D image-based BT