Is SBRT Boost Feasible for PET Positive Lymph Nodes for Cervical Cancer? Evaluation using Tumor Control Probability and QUANTEC Criteria.

This study aimed to examine the feasibility of stereotactic body radiation therapy (SBRT) as an external beam radiation therapy boost to positron emission tomography (PET) positive lymph nodes (LN) in patients with cervical cancer and to evaluate overall tumor control probability (TCP) increase. Ten patients with cervical cancer and PET positive LN metastasis who received external beam radiation therapy (45 Gy), followed by a 3-dimensional conformal radiation therapy boost (5.4-9 Gy) and tandem-and-ovoid high-dose-rate brachytherapy (16-30 Gy) were retrospectively enrolled in this study. SBRT plans were generated using 21 Gy, 24 Gy, or 30 Gy as a replacement for 3-dimensional conformal radiation therapy boost. The 2 Gy-per-fraction equivalent dose maps were made using an α/β value of 10 for PET positive LNs and 3 for organs at risk (OARs). TCP values were calculated using a logistic TCP model, where 2 input parameters (D50 and Gamma50 = 2) were modeled by 2 clinical outcomes: our institution and the literature. OAR sparing was evaluated using Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) dose limits. Thirty percent of 10 patients receiving conventional boost experienced recurrence. The TCP of the SBRT schemes was 88% ± 7% (97% ± 2%; 21 Gy), 96% ± 1% (99% ± 0%; 24 Gy), and 99% ± 1% (100% ± 0%; 30 Gy), and the conventional LN-boost TCP value was 25% ± 11% (58% ± 15%) when TCP input parameters were based on published clinical outcome data for LN SBRT treatments (institutional outcome data). The tumor coverage doses (D90) of the SBRT boost plans were on average 32.34 Gyαβ=10 (21 Gy), 37.78 Gyαβ=10 (24 Gy), and 55.54Gyαβ=10 (30 Gy) higher than the conventional LN boost plan. The QUANTEC OAR dose constraints were met for the bladder, rectum, and bowel in all cases for the SBRT LN 21 Gy group, and in 90% and 70% of cases in the SBRT LN 24 Gy and SBRT LN 30 Gy groups, respectively. An SBRT boost dose of 30 Gy can be delivered without compromising QUANTEC OAR limits. The use of SBRT increases TCP values, regardless of the input parameters.

Snyder JE ，Willett AB ，Sun W ，Kim Y ... -  《-》

Extended field intensity modulated radiation therapy with concomitant boost for lymph node-positive cervical cancer: analysis of regional control and recurrence patterns in the positron emission tomography/computed tomography era.

Positron emission tomography/computed tomography (PET/CT) is commonly used for nodal staging in locally advanced cervical cancer; however the false negative rate for para-aortic disease are 20% to 25% in PET-positive pelvic nodal disease. Unless surgically staged, pelvis-only treatment may undertreat para-aortic disease. We have treated patients with PET-positive nodes with extended field intensity modulated radiation therapy (IMRT) to address the para-aortic region prophylactically with concomitant boost to involved nodes. The purpose of this study was to assess regional control rates and recurrence patterns. Sixty-one patients with cervical cancer (stage IBI-IVA) diagnosed from 2003 to 2012 with PET-avid pelvic nodes treated with extended field IMRT (45 Gy in 25 fractions with concomitant boost to involved nodes to a median of 55 Gy in 25 fractions) with concurrent cisplatin and brachytherapy were retrospectively analyzed. The nodal location was pelvis-only in 41 patients (67%) and pelvis + para-aortic in 20 patients (33%). There were a total of 179 nodes, with a median number of positive nodes of 2 (range, 1-16 nodes) per patient and a median nodal size of 1.8 cm (range, 0.7-4.5 cm). Response was assessed by PET/CT at 12 to 16 weeks. Complete clinical and imaging response at the first follow-up visit was seen in 77% of patients. At a mean follow-up time of 29 months (range, 3-116 months), 8 patients experienced recurrence. The sites of persistent/recurrent disease were as follows: cervix 10 (16.3%), regional nodes 3 (4.9%), and distant 14 (23%). The rate of para-aortic failure in patients with pelvic-only nodes was 2.5%. There were no significant differences in recurrence patterns by the number/location of nodes, largest node size, or maximum node standardized uptake value. The rate of late grade 3+ adverse events was 4%. Extended field IMRT was well tolerated and resulted in low regional recurrence in node-positive cervical cancer. The dose of 55 Gy in 25 fractions was effective in eradicating disease in involved nodes, with acceptable late adverse events. Distant metastasis is the predominant mode of failure, and the OUTBACK trial may challenge the presented paradigms.

Vargo JA ，Kim H ，Choi S ，Sukumvanich P ，Olawaiye AB ，Kelley JL ，Edwards RP ，Comerci JT ，Beriwal S ... -  《-》

Less Than Whole Uterus Irradiation for Locally Advanced Cervical Cancer Maintains Locoregional Control and Decreases Radiation Dose to Bowel.

This study aimed to evaluate whether our institutional standard of less-than-whole-uterus irradiation affects locoregional control in patients with locally advanced cervical cancer. We retrospectively reviewed 53 patients with stage IB to IVB cervical carcinoma who were treated with image guided intensity modulated radiation therapy and brachytherapy. The entire uterus was not included in the clinical target volume, as per our institutional standard. Dosimetric parameters were obtained, including positron emission tomography gross tumor volume (GTV), uterus volume excluding GTV, proportion of uterus included in the planning target volume (PTV; percentage), volume of overlap between uterus and prescription dose (cm3), minimum and mean dose to the uterus, and bowel V40 and D200cc. Local, regional, and distant failure and death were recorded. The median proportion of the uterus included in the PTV was 66%. With a median follow-up of 44 months, no patient experienced isolated local recurrence, and 2-year locoregional failure was 10.9%. Positron emission tomography GTV correlated significantly with increased chance of any failure (P = .049; 95% confidence interval, 1.000-1.018). Compared with patients who had ≥90% of the uterus included in the PTV (n = 12), patients who had <90% (n = 41) of the uterus included in the PTV had significantly lower bowel V40 (P = .049) and D200cc (P = .006). Less-than-whole-uterus irradiation for locally advanced cervical cancer does not compromise locoregional control and reduces bowel V40 and D200cc. Further investigation is required to evaluate whether this reduction in bowel dose translates to a clinically significant reduction in bowel toxicity and whether modifications should be made to the recommended definitive cervix intensity modulated radiation therapy volumes.

Kozak MM ，Koenig JL ，von Eyben R ，Kidd EA ... -  《-》

IMRT with ¹⁸FDG-PET\CT based simultaneous integrated boost for treatment of nodal positive cervical cancer.

Cihoric N ，Tapia C ，Krüger K ，Aebersold DM ，Klaeser B ，Lössl K ... -  《-》

Proof of principle: Applicator-guided stereotactic IMRT boost in combination with 3D MRI-based brachytherapy in locally advanced cervical cancer.

To describe a new technique involving high-precision stereotactic intensity-modulated radiation therapy (IMRT) boost in combination with intracavitary-interstitial (IC-IS) brachytherapy (BT) in cervical tumors that cannot be sufficiently covered by IC-IS-BT due to extensive residual disease and/or difficult topography at the time of BT. Three patients with stage IIIB-IVA cervical cancer had significant residual disease at the time of BT. MRI-guided IC-IS-BT (pulsed-dose rate) was combined with a stereotactic IMRT boost guided according to the BT applicator in situ, using cone beam CT. The planning aim dose (total external beam radiotherapy and BT) for the high-risk clinical target volume (HR-CTV) was D90 >70-85 Gy, whereas constraints for organs at risk were D2cm3 <70 Gy for rectum, sigmoid, and bowel and <90 Gy for bladder in terms of equivalent total dose in 2 Gy fractions. An IMRT boost adapted to the BT dose distribution was optimized to target the regions poorly covered by BT. HR-CTV doses of D90 >81 Gy were obtained in the central HR-CTV and D90 >69 Gy in the distal regions of HR-CTV. Image-guided set up of the IMRT boost with the applicator in situ was feasible. The dose plans were robust to intra-fraction uncertainties of 3 mm. Local control with acceptable morbidity was obtained at a followup of 3, 2.5, and 1 year, respectively. The combination of MRI-guided BT with an applicator-guided stereotactic IMRT boost is feasible. This technique seems to be useful in the few cases where HR-CTV coverage cannot be obtained even with IS-IC-BT.

Assenholt MS ，Vestergaard A ，Kallehauge JF ，Mohamed S ，Nielsen SK ，Petersen JB ，Fokdal L ，Lindegaard JC ，Tanderup K ... -  《-》