Intermediate dose-volume parameters and the development of late rectal toxicity after MRI-guided brachytherapy for locally advanced cervix cancer.

The dose delivered to the most exposed 2 cm3 [Formula: see text] of the rectum and bladder is predictive of late rectal and bladder toxicity in cervix cancer patients. We investigated the predictive value of intermediate doses to the rectum and bladder for late rectal/bladder toxicity after MRI-guided brachytherapy for patients with locally advanced cervix cancer. Toxicity was prospectively graded using Common Toxicity Criteria for Adverse Events v4.0 and retrospectively verified for women with Stage IB-IVA cervix cancer treated consecutively with MRI-guided brachytherapy between 2008 and 2013. The minimum equivalent dose in 2 Gy fractions delivered to 0.1, 1, 2, 5, and 10 cm3 of the rectum and bladder and the absolute volume of the rectum receiving 55, 60, 65, 70, and 75 Gy3 (V55-75) were collected. The association between dose-volume parameters and Grade 2+ rectal/bladder toxicity was examined using logistic regression. With a median followup of 44 months, cumulative incidences of Grade 2+ rectal and bladder toxicity among the 106 patients were 29% and 15% at 3 years, respectively. All the dose-volume parameters were significantly associated with late Grade 2+ rectal and bladder toxicity (p < 0.05), except for bladder [Formula: see text] . On multivariable logistic regression, both [Formula: see text]  > 70 Gy3 and V55 > 11 cm3 (p < 0.05) were predictive of late Grade 2+ rectal toxicity, with improved model fitting and higher area under the curve compared with the model with [Formula: see text]  > 70 Gy3 alone. In this study, V55 was predictive of late Grade 2+ rectal toxicity. Adding V55 to  [Formula: see text] improved prediction accuracy.

Ujaimi R ，Milosevic M ，Fyles A ，Beiki-Ardakani A ，Carlone M ，Jiang H ，Lindsay P ，Xie J ，Gerber R ，Croke J ，Skliarenko J ，Levin W ，Han K ... -  《-》

Risk of Late Urinary Complications Following Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: Refining Bladder Dose-Volume Parameters.

To study correlations between dose-volume parameters of the whole bladder and bladder trigone and late urinary toxicity in locally advanced cervical cancer patients treated with pulsed-dose-rate brachytherapy. Patients with locally advanced cervical cancer treated with chemoradiation therapy and pulsed-dose-rate brachytherapy from 2004 to 2015 were included. Cumulative dose-volume parameters of the whole bladder and bladder trigone were converted into 2-Gy/fraction equivalents (EQD2, with α/β = 3 Gy); these parameters, as well as clinical factors, were analyzed as predictors of toxicity in patients without local relapse. A total of 297 patients fulfilled the inclusion criteria. The median follow-up period was 4.9 years (95% confidence interval 4.5-5.3 years). In patients without local relapse (n = 251), the Kaplan-Meier estimated grade 2 or higher urinary toxicity rates at 3 years and 5 years were 25.4% and 32.1%, respectively. Minimal dose to the most exposed 2 cm3 of the whole bladder [Formula: see text] , bladder International Commission on Radiation Units & Measurements (ICRU) (BICRU) dose, and trigone dose-volume parameters correlated with grade 2 or higher toxicity. At 3 years, the cumulative incidence of grade 2 or higher complications was 22.8% (standard error, 2.9%) for bladder [Formula: see text]  < 80 GyEQD2 versus 61.8% (standard error, 12.7%) for [Formula: see text]  ≥ 80 GyEQD2 (P = .001). In the subgroup of patients with bladder [Formula: see text]  ≤ 80 GyEQD2, a trigone dose delivered to 50% of the volume (D50%) > 60 GyEQD2 was significant for grade 2 or higher toxicity (P = .027). The probability of grade 3 or higher toxicities increased with bladder [Formula: see text]  > 80 GyEQD2 (16.7% vs 1.6%; hazard ratio [HR], 5.77; P = .039), BICRU dose > 65 GyEQD2 (4.9% vs 1.3%; HR, 6.36; P = .018), and trigone D50% > 60 GyEQD2 (3.1% vs 1.2%; HR, 6.29; P = .028). Pearson correlation coefficients showed a moderate correlation between bladder [Formula: see text] , BICRU dose, and bladder trigone D50% (P < .0001). These data suggest that [Formula: see text]  ≤ 80 GyEQD2 should be advised for minimizing the risk of severe urinary complications (<15%). Bladder trigone dose was also predictive of severe late urinary toxicity. These constraints need further confirmation in a multicenter prospective setting.

Manea E ，Escande A ，Bockel S ，Khettab M ，Dumas I ，Lazarescu I ，Fumagalli I ，Morice P ，Deutsch E ，Haie-Meder C ，Chargari C ... -  《-》

Long term experience with 3D image guided brachytherapy and clinical outcome in cervical cancer patients.

To report our 10years' experience and learning curve of the treatment of cervical cancer patients with chemo radiotherapy and MRI (or CT in 9 selected patients) guided brachytherapy using pulsed dose rate (PDR) brachytherapy (BT). Hundred and seventy consecutive patients with cervical cancer FIGO stage IB-IVB (without metastases beyond the para-aortic nodal region) were treated in our institute between 2002 and 2012. Patients received external beam radiotherapy (nodal boost to the lymph nodes positive at diagnosis)±chemotherapy followed by a pulsed or low dose rate brachytherapy boost. MRI (or CT) images were taken with the applicator in situ. The first 16 patients were treated according to X-ray-based plans, optimized on MRI. High-risk CTV, intermediate-risk CTV, bladder, rectum and sigmoid were retrospectively contoured according to the GEC-ESTRO recommendations. In all other patients, treatment plans were optimized after delineation of the target volumes and organs at risk at MRI (or CT). Doses were converted to the equivalent dose in 2Gy (EQD2) by applying the linear quadratic model. The median age of the patients was 55years (range 16-88). 41% had stage III or IV disease. Of the 170 patients, 91 patients had on imaging metastatic lymph nodes at diagnosis (62 patients pelvic lymph node involvement and 29 para-aortic). In 27 (16%) patients the intracavitary technique was combined with interstitial brachytherapy. The mean D90 and D100 for the high-risk CTV were 84.8±8.36Gy and 67.5±6.29Gy for the entire patient group. Mean D90 and D100 values for the IR CTV were 68.7±5.5Gy and 56.5±6.25Gy. There was an important learning curve between both patient groups, with an increase in mean D90 of 75.8Gy for the first 16 patients compared to 85.8Gy for the second group. At the same time, the mean dose to 2cm3 of bladder and sigmoid decreased from 86.1Gy to 82.7Gy and from 70Gy to 61.7Gy, respectively. At a median follow-up of 37months (range 2-136months), local control rate for all patients was 96%, the regional control (pelvic and para-aortic) rate 81% and crude disease free survival rate 55%. The overall survival at 5years is 65%. The higher dose to the target volume resulted in an increase in local control from 88% in the first 16 patients compared to 97% in the second patient group. Regarding late toxicity, 21 patients (12%) presented grade 3-4 late morbidity. Rectal, urinary, sigmoid and vaginal morbidity was 5%, 6%, 2% and 5%, respectively. A correlation between rectal D2cm3 >65Gy and grade >3 late morbidity was found (p=0.006). Although the majority of the patients presented with locally advanced carcinoma, excellent local and regional control rates were achieved. Rectal, urinary, sigmoid and vaginal grade 3-4 morbidity was 5%, 6%, 2% and 5%, respectively. A correlation between rectal D2cm3 >65Gy and grade >3 late morbidity was found (p=0.006).

Ribeiro I ，Janssen H ，De Brabandere M ，Nulens A ，De Bal D ，Vergote I ，Van Limbergen E ... -  《-》

Bladder accumulated dose in image-guided high-dose-rate brachytherapy for locally advanced cervical cancer and its relation to urinary toxicity.

Zakariaee R ，Hamarneh G ，Brown CJ ，Gaudet M ，Aquino-Parsons C ，Spadinger I ... -  《-》

Effect of bladder distension on doses to organs at risk in Pulsed-Dose-Rate 3D image-guided adaptive brachytherapy for locally advanced cervical cancer.

To evaluate the impact of bladder distension on doses to organs at risk in patients treated with 3D image-guided adaptive pulsed-dose-rate (PDR) brachytherapy (BT) for locally advanced cervical cancer. Twenty-two patients who had previously been treated by external beam radiation therapy (EBRT), underwent BT treatment planning to a pelvic MRI (or a CT scan in case of contraindication) after their bladder was filled with 100 cc of physiological saline (full bladder). This was immediately followed by a CT scan after emptying of the bladder. A fusion of these two examinations was conducted, and the dosimetry was duplicated for the study with an empty bladder. Equieffective doses of 2 Gy per fraction from EBRT and BT of bladder/rectum/sigmoid colon/small bowel were compared. A full bladder condition was found to be non-inferior in terms of the bladder D2cc (a difference of -0.9 Gy; 97.5% CI [-∞; 2.6]), and it resulted in a reduction in the bladder D0.1cc (p = 0.038). Bladder expansion resulted in a significant reduction of maximum doses received by the small bowel, both in terms of the D0.1cc (51.2 Gy vs. 63.4 Gy, p < 0.001) and the D2cc (48.5 Gy vs. 53.6 Gy, p < 0.001). A negative correlation was seen between the difference in the small bowel D2cc and the body mass index; (r = -0.55; p = 0.008). No differences were noted in regard to doses to the rectum and sigmoid colon. Bladder distension with 100 cc of physiological saline can reduce maximum doses received by the small bowel without the alteration of the doses received by the other organs at risk during a 3D image-guided adaptive PDR BT for locally advanced cervical cancer. However, the maintenance of a predefined bladder volume is difficult to achieve with PDR BT, whereas it could be easily managed before each session in case of high-dose-rate BT.

Nesseler JP ，Charra-Brunaud C ，Salleron J ，Py JF ，Huertas A ，Meknaci E ，Courrech F ，Peiffert D ，Renard-Oldrini S ... -  《-》