The impact of modern preoperative high-dose-rate brachytherapy in early-stage cervical cancer.

PURPOSE: To analyze the clinical outcomes and the safety of preoperative high-dose-rate (HDR) image-guided adaptive brachytherapy (IGABT) followed by minimally invasive surgery (MIS) in the multidisciplinary management of early-stage cervical cancer. METHODS AND MATERIALS: Medical records of all consecutive patients with early-stage cervical cancer treated at our institution between 2012 and 2018 with preoperative IGABT in a multidisciplinary approach were reviewed. Treatment schedule was pelvic node dissection, preoperative IGABT followed 6-8 week later by MIS hysterectomy. RESULTS: Seventy patients with cervical cancer FIGO stages (IB1 18.6%, IB2 75.7% and IIA1 5.7%) were treated by preoperative HDR brachytherapy. With a median follow-up of 37.4 months [95% confidence interval, 32.1-39.7 months] isolated vaginal vault recurrence was not observed, 3 pelvic relapses were reported (4.3%). None of patients received postoperative radiotherapy (EBRT) or radiochemotherapy. The estimated 3-year local and pelvis relapse free survival for the entire population were respectively 98% [95% confidence interval, 89%-100%] and 90% [80%-96%]. The estimated 3-year disease-free survival (DFS) for the entire population was 88% [77-94%]. The 3-year overall survival (OS) rate was 97% [88%-99%]. Microscopic vaginal resection margin (R1) was observed in one patient ([1].4%). Lymph-vascular space invasion (LVSI) was found found in 6 (8.6%) patients. Forty-eight late complications in 36 patients (51.4%) were observed. Five (7.1%) grade 3 vaginal wound dehiscence toxicities were observed. Urinary and gastrointestinal toxicities were grade 1-2. No grade 4-5 complications were observed. CONCLUSIONS: Preoperative image-guided adaptive brachytherapy followed by minimally invasive surgery allows high local control, reduces positive surgical margins and rates of lymph-vascular space invasion avoiding adjuvants treatments. Surgical approaches must be discussed with patients including preoperative brachytherapy as a down-staging treatment.

Lessons from radiochemotherapy and modern image-guided adaptive brachytherapy followed by hysterectomy.

PURPOSE: To analyze the clinical outcomes and the safety of radiochemotherapy (RCT) and image-guided adaptive brachytherapy (IGABT) and to evaluate the impact of hysterectomy (HT) as completion of treatment for cervical cancer. METHODS AND MATERIALS: 145 patients with locally advanced cervical cancer were treated at our institution. Patients underwent RCT and IGABT, then hysterectomy (HT) as completion of treatment was performed, with the exception of patients with surgical contraindications, para aortic metastatic disease or patients who refused surgery. Clinical outcomes and morbidity were retrospectively reviewed in both groups. Local relapse free survival (LRFS), pelvic relapse free survival (PRFS) and overall survival (OS) were analyzed. RESULTS: Completion HT was performed in 90 (62.1%) patients. Complete histological response and microscopic disease were found in 77 patients (85.6%). Local relapse was observed in 14 patients (9.6%) without differences between completion HT group and the definitive RCT and IGABT group (Odds Ratio OR = 1.73 [0.57-5.23], p = 0.33). The estimated 3-year LRFS and PRFS for the entire population were respectively 90% [84%-94%] and 93% [87%-96%], with no significant differences between them (respectively Hazard Ratio HR = 0.57 [0.20-1.64], p = 0.30 and HR = 0.37 [0.10-1.31], p = 0.12). The estimated 3-year OS rate for the whole population was 84% [75%-91%] with no significant differences between groups (HR = 0.81 [0.32-2.06], p = 0.65). Regarding morbidity, grade ≥ 2 vaginal toxicity was more frequent in the definitive RCT and IGABT group (43.6% vs 26.7%, p = 0.04). All grade 4 toxicity events were reported in the completion HT group. CONCLUSIONS: Due to high severe toxicity, RCT and IGABT with dose escalation followed by completion hysterectomy don't seem compatible. No benefit and increased severe late morbidity were observed. Combined intracavitary/interstitial technique is mandatory in large target volume at brachytherapy.

Safety and benefit of using a virtual bolus during treatment planning for breast cancer treated with arc therapy.

PURPOSE: This study evaluates the benefit of a virtual bolus method for volumetric modulated arc therapy (VMAT) plan optimization to compensate breast modifications that may occur during breast treatment. METHODS: Ten files were replanned with VMAT giving 50 Gy to the breast and 47 Gy to the nodes within 25 fractions. The planning process used a virtual bolus for the first optimization, then the monitors units were reoptimized without bolus, after fixing the segments shapes. Structures and treatment planning were exported on a second scanner (CT) performed during treatment as a consequence to modifications in patient's anatomy. The comparative end-point was clinical target volume's coverage. The first analysis compared the VMAT plans made using the virtual bolus method (VB-VMAT) to the plans without using it (NoVB-VMAT) on the first simulation CT. Then, the same analysis was performed on the second CT. Finally, the level of degradation of target volume coverage between the two CT using VB-VMAT was compared to results using a standard technique of forward-planned multisegment technique (Tan-IMRT). RESULTS: Using a virtual bolus for VMAT does not degrade dosimetric results on the first CT. No significant result in favor of the NoVB-VMAT plans was noted. The VB-VMAT method led to significant better dose distribution on a second CT with modified anatomies compared to NoVB-VMAT. The clinical target volume's coverage by 95% (V95%) of the prescribed dose was 98.9% [96.1-99.6] on the second CT for VB-VMAT compared to 92.6% [85.2-97.7] for NoVB-VMAT (P = 0.0002). The degradation of the target volume coverage for VB-VMAT is not worse than for Tan-IMRT: the median differential of V95% between the two CT was 0.9% for VMAT and 0.7% for Tan-IMRT (P = 1). CONCLUSION: This study confirms the safety and benefit of using a virtual bolus during the VMAT planning process to compensate potential breast shape modifications.

Does Breast Surgery Type Alter Incidental Axillary Irradiation? A Dosimetric Analysis of the "Sentinel Envahi et Randomisation du Curage" SERC Trial.

BACKGROUND: An incidental axillary dose of adjuvant radiotherapy using tangential beams is usually given after breast-conserving surgery for breast cancer. The goal of this sub-study was to evaluate this incidental dose in the setting of post-mastectomy radiotherapy (PMRT) according to two different radiotherapy techniques. METHODS: Patients participating in a randomized SERC trial who received PMRT in a single center were included. We collected the incidental axillary dose delivered to the Berg level 1 using different dosimetric parameters and compared two techniques using Student's t-test: three-dimensional conformal radiotherapy (3D-CRT) and volumetric arc therapy (VMAT). RESULTS: We analyzed radiotherapy plans from 52 patients who received PMRT from 2012 to 2021. The mean dose delivered to the Berg level 1 was 37.2 Gy. It was significantly higher with VMAT than with 3D-CRT-43.6 Gy (SD = 3.1 Gy) versus 34.8 Gy (SD = 8.6 Gy) p < 0.001. Eighty-four percent of the Berg level 1 was covered by 40 Gy isodose in the VMAT group versus 55.5% in the 3D-CRT group p < 0.001. CONCLUSIONS: On the Berg level 1, PMRT gives a dose at least equivalent to the one given by post-breast-conserving surgery radiotherapy, making it possible to limit completion axillary lymph node dissections in select pN1a patients treated with a mastectomy. Modern radiotherapy techniques like VMAT tend to increase this incidental dose.

The impact of brachytherapy boost for anal canal cancers in the era of de-escalation treatments.

PURPOSE: To analyze clinical outcomes of high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) for the treatment of anal canal cancers (ACC). METHODS AND MATERIALS: A total of 78 patients with ACC were treated at our institution by ISBT. Local Control (LC), disease-free survival (DFS), overall survival (OS), colostomy-free survival (CFS) and toxicity rates were analyzed. RESULTS: With a median followup (FU) of 59.8 months (95% CI [55.8-64.2]), six (7.7%) local recurrences with 2 patients (2.6%) having persistent disease at 3 months were observed. The 5-year rate of LC for the entire population was 92% [83-96%]. The 5-year DFS rate was 86% [76-93%]. The 5-year OS was 96% [88-99%]. In the univariate analysis, chemotherapy was significantly associated with morbidity grade ≥2. Late digestive toxicity grade ≥3 was reported in 8.9% patients, 1 patient underwent colostomy due to toxicity. The 5-year CFS rate was 88% [79-94%]. CONCLUSIONS: HDR interstitial brachytherapy boost provide excellent rates of tumor control and colostomy-free survival with a favorable profile of GI toxicity. Continence in anal cancer survivors is a challenge and the boost technique must be discussed in a multidisciplinary approach as part of de-escalation treatments.

Reducing dose to rectum by placement of a rectum-emptying tube in cervical cancer patients treated with brachytherapy.

PURPOSE: Only scarce data are available on the possibility to reduce rectal dose by controlling rectum filling before HDR (high dose rate) IGABT (image-guided adaptive brachytherapy) in LACC (locally advanced cervical carcinoma) patients. We compared dosimetric outcomes before and after the evacuation of gasses using a rectum emptying tube. METHODS AND MATERIAL: Sixty CT (computed tomography) scans from 30 consecutive patients with cancer of the cervix undergoing HDR IGABT after EBRT were reviewed. Patients who underwent at least one gas evacuation were included in the analysis. The three-dimensional dosimetric data of the dosimetric plan performed before and after gas evacuation were compared. Primary endpoint was the difference between D2cc of the rectum before and after the procedure. Expected probability of grade 2-4 overall rectum morbidity was assessed using a probit model from the prospective multicenter EMBRACE study. RESULTS: Thirty five (58.3%) CT scans from 23 patients (76.7%) requiring gas evacuation were analysed. The mean rectum volume, before and after gas evacuation, was 123.1 cc (sd, ± 60.4) and 66.4 cc (sd, ± 34.8), respectively. For each patient, the volume of the rectum after gas evacuation was lower than before. No major complication occurred during and after the procedure. After gas evacuation, a significant reduction in rectal dose per fraction was observed, on average -4.3 Gy (-38.4%, p < 0.001) for D0.1cc and -1.9 Gy (-30.6%, p < 0.001) for D2cc. Estimated mean probability to develop a grade 2-4 rectum morbidity was significantly lower after gas evacuation, 6.9% (sd,± 1.94) versus 9.5% (sd,± 3.17), p < 0.001. CONCLUSION: Gas evacuation using a rectal emptying tube in selected LACC patients treated with HDR BT after chemoradiotherapy, allowed a substantial reduction in the dose to the rectum. Such procedure could be of particular interest when a dose escalation strategy is being considered.

High-dose-rate vs. low-dose-rate interstitial brachytherapy boost for anal canal cancers.

PURPOSE: The purpose of this study was to analyze and compare clinical outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after EBRT or radio chemotherapy for the treatment of anal canal cancers. METHODS AND MATERIALS: One hundred patients with anal canal cancers were treated at our institution by ISBT [LDR (n = 50); HDR (n = 50)]. Chronic toxicity rates, local control, disease-free survival, overall survival, and colostomy-free survival of the two different dose-rate brachytherapy modalities were analyzed and compared. RESULTS: With a median followup of 42.2 months (95% CI, [34.5-48.8]), 9 (9% [4.8-16.2%]) local recurrences were observed, 4 (8% [3.2-18.8%]) in LDR vs. 5 (10% [4.4-21.4%]) in HDR group (odds ratio [OR] = 1.28 [0.32-5.07], p = 0.73). The 5-year rate of local control for the entire population was 90% [81-95%], 93% [79-98%] vs. 86% [69-94%] for LDR and HDR, respectively (p = 0.38). The 5-year disease-free survival rate for all patients was 82% [71-90%], 88% [73-95%] vs. 72% [44-88%] for LDR and HDR, respectively (p = 0.21). The 5-year overall survival rate for global population was 94% [84-98%], with no significant differences between LDR (97% [79-100%]) and HDR (93% [80-98%]) (p = 0.27). The 5-year colostomy-free survival rate was 92% [83-96%], respectively, 95% [83-99%] vs. 86% [69-94%] for LDR and HDR (p = 0.21). Significant differences were found in terms of chronic toxicity rates, with 28 (56% [42.3-68.8%]) patients concerned in low-dose-rate brachytherapy vs. 17 (34% [22.4-47.9%]) in high-dose-rate brachytherapy (OR = 0.40 [0.18-0.91], p = 0.03). CONCLUSIONS: Local recurrence rates were comparable between both groups; HDR brachytherapy seem to have a better toxicity profile. Our data confirmed the finding that HDR can be used to safely administer ISBT without increasing chronic toxicity.

Multivariate normal tissue complication probability modeling of vaginal late toxicity after brachytherapy for cervical cancer.

PURPOSE: To explore the best variables combination for a predictive model of vaginal toxicity in cervical cancer patients undergoing brachytherapy (BT). METHODS AND MATERIALS: Clinical and 3-dimensional dosimetric parameters were retrospectively extracted from an institutional database of consecutive patients undergoing intracavitary BT after external beam radiation therapy from 2006 to 2013 for a cervical cancer. A least absolute shrinkage and selection operator selection procedure in Cox's proportional hazards regression model was performed to select a set of relevant predictors for a multivariate normal tissue complication probability model of Grade ≥2 vaginal late toxicity. Outcomes reliability was internally assessed by bootstrap resampling method. RESULTS: One hundred sixty-nine women were included in the present study with a median followup time of 3.8 years (interquartile range [IQR], 1.9-5.6 years). The 2 years and 5 years cumulative incidence rates of Grade ≥2 late vaginal toxicity were 19.9% and 27.5%, respectively. Among 31 metrics and six clinical factors extracted, the optimal model included two dosimetric variables: V70Gy and D5% (the percentage volume that received a dose greater or equal to 70 Gy and the minimum dose given to the hottest 5% volume, respectively). Area under the ROC curve at 2 and 5 years of followup were 0.85 and 0.91, respectively. Regarding internal validation, median area under the ROC curve of bootstrap predictions was 0.83 (IQR, 0.78-0.88) and 0.89 (IQR, 0.85-0.93) at 2 and 5 years of followup, respectively. CONCLUSIONS: A multivariate normal tissue complication probability model for severe vaginal toxicity based on two dosimetric variables (V70Gy and D5%) provides reliable discrimination capability in a cohort of cervical cancer treated with external beam radiation therapy and BT.