Pulsed Dose Rate Brachytherapy of Lip Carcinoma: Clinical Outcome and Quality of Life Analysis.

PURPOSE: Lip carcinoma represents one of the most common types of head and neck cancer. Brachytherapy is a highly effective therapeutic option for all stages of lip cancers. We report our experience of pulsed dose rate brachytherapy (PDR) as treatment of lip carcinoma. METHODS AND MATERIALS: this retrospective single center study included all consecutive patients treated for a lip PDR brachytherapy in our institution from 2010 to 2019. The toxicities and outcomes of the patients were reported, and a retrospective quality of life assessment was conducted by phone interviews (FACT H&N). RESULTS: From October 2010 to December 2019, 38 patients were treated in our institution for a lip carcinoma by PDR brachytherapy. The median age was 73, and the majority of patients presented T1-T2 tumors (79%). The median total dose was 70.14 Gy (range: 60-85 Gy). With a mean follow-up of 35.4 months, two patients (5.6%) presented local failure, and seven patients (19%) had lymph node progression. The Kaplan-Meier estimated probability of local failure was 7.2% (95% CI: 0.84-1) at two and four years. All patients encountered radiomucitis grade II or higher. The rate of late toxicities was low: three patients (8.3%) had grade II fibrosis, and one patient had grade II chronic pain. All patients would highly recommend the treatment. The median FACT H&N total score was 127 out of 148, and the median FACT H&N Trial Outcome Index was 84. CONCLUSIONS: This study confirms that an excellent local control rate is achieved with PDR brachytherapy as treatment of lip carcinoma, with very limited late side effects and satisfactory functional outcomes. A multimodal approach should help to improve regional control.

Radiobiological optimization comparison between pulse-dose-rate and high-dose-rate brachytherapy in patients with locally advanced cervical cancer.

PURPOSE: Only scarce data are available on the possibility to include radiobiological optimization as part of the dosimetric process in cervical cancer treated with brachytherapy (BT). We compared dosimetric outcomes of pulse-dose-rate (PDR) and high-dose-rate (HDR)-BT, according to linear-quadratic model. METHODS AND MATERIALS: Three-dimensional dosimetric data of 10 consecutive patients with cervical cancer undergoing intracavitary image-guided adaptive PDR-BT after external beam radiation therapy were examined. A new HDR plan was generated for each patient using the same method as for the PDR plan. The procedure was intended to achieve the same D90 high-risk clinical target volume with HDR as with PDR planning after conversion into dose equivalent per 2 Gy fractions (EQD2) following linear-quadratic model. Plans were compared for dosimetric variables. RESULTS: As per study's methodology, the D90 high-risk clinical target volume was strictly identical between PDR and HDR plans: 91.0 Gy (interquartile: 86.0-94.6 Gy). The median D98 intermediate-risk clinical target volume was 62.9 GyEQD2 with HDR vs. 65.0 GyEQD2 with PDR (p < 0.001). The median bladder D2cc was 65.6 GyEQD2 with HDR, vs. 62 GyEQD2 with PDR (p = 0.004). Doses to the rectum, sigmoid, and small bowel were higher with HDR plans with a median D2cc of 55.6 GyEQD2 (vs. 55.1 GyEQD2, p = 0.027), 67.2 GyEQD2 (vs. S 64.7 GyEQD2, p = 0.002), and 69.4 GyEQD2 (vs. 66.8 GyEQD2, p = 0.014), respectively. For organs at risk (OARs), the effect of radiobiological weighting depended on the dose delivered. When OARs BT contribution to D2cc doses was <20 GyEQD2, both BT modalities were equivalent. OARs EQD2 doses were all higher with HDR when BT contribution to D2cc was ≥20 GyEQD2. CONCLUSION: Both BT modalities provided satisfactory target volume coverage with a slightly higher value with the HDR technique for OARs D2cc while intermediate-risk clinical target volume received higher dose in the PDR plan. The radiobiological benefit of PDR over HDR was predominant when BT contribution dose to OARs was >20 Gy.

Image-guided adaptive brachytherapy in primary vaginal cancers: A monocentric experience.

PURPOSE: Primary vaginal cancer is a rare disease for which treatment has been modeled based on cervical cancer. We report our experience in the use of image-guided adaptive brachytherapy (IGABT) in this indication. METHODS AND MATERIALS: Patients treated for vaginal cancer with a combination of external beam radiation therapy and IGABT were identified through electronic search. The Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology recommendations for cervical cancer have been extrapolated with the definition of two clinical target volumes (CTVs) corresponding to the residual disease after external beam radiation therapy (CTVBT), assessed from clinical and imaging findings, and the so-called CTVi, comprising the CTVBT with directional margins and at least the initial disease at diagnosis. RESULTS: Twenty-seven patients were identified. MRI was used for brachytherapy guidance in 82% of the cases. An interstitial component was used in 59% of the cases. The D90 CTVBT and D90 CTVi were 73.1 ± 12.8 Gy and 66.6 ± 6.7 Gy, respectively. After a median followup of 40.1 months, nine recurrences in 8 patients were observed of which four were local. Local relapses occurred within the CTVBT. Three-year local control and disease-free rates were 82% and 65%, respectively. At 2 years, the Grade 2-4 gastrointestinal or urinary morbidity accrual rate was 9%. Twelve patients experienced late sexual morbidity, including three patients with Grade 3 stenosis. CONCLUSION: IGABT is feasible in vaginal cancer with promising outcomes. Harmonizing the definition of CTVs is required to allow comparisons between experiences and to perform multicenter studies.

MRI-guided brachytherapy in locally advanced cervical cancer: Small bowel [Formula: see text] and [Formula: see text] are not predictive of late morbidity.

PURPOSE: To establish dose-volume effect correlations for late small bowel (SB) toxicities in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate MRI-guided adaptive brachytherapy. METHODS AND MATERIALS: Patients treated with curative intent and followed prospectively were included. The SB loops closed to CTV were delineated, but no specific dose constraint was applied. The dosimetric data, converted in 2-Gy equivalent, were confronted with the occurrence of late morbidity assessed using the CTC-AE 3.0. Dose-effect relationships were assessed using mean-dose comparisons, log-rank tests on event-free periods, and probit analyses. RESULTS: A total of 115 patients with a median followup of 35.5 months were included. Highest grade per patient was: Grades 0 for 17, 1 for 75, 2 for 20, and 3 for 3. The mean [Formula: see text] and [Formula: see text] were, respectively, 68.7 ± 13.6 Gy and 85.8 ± 33.1 Gy and did not differ according to event severity (p = 0.47 and p = 0.52), even when comparing Grades 0-1 vs. 2-4 events (68.0 ± 12.4 vs. 71.4 ± 17.7 Gy; p = 0.38 and 83.7 ± 26.4 vs. 94.5 ± 51.9 Gy; p = 0.33). Log-rank tests were performed after splitting the cohort according to four [Formula: see text] levels: >80 Gy, 70-79 Gy, 60-70 Gy, and <60 Gy. No difference was observed for Grades 1-4, Grades 2-4, or Grades 3-4 (p = 0.21-0.52). Probit analyses showed no correlation between the dosimetric parameters and probability of Grades 1-4, 2-4, or 3-4 events (p = 0.19-0.48). CONCLUSION: No significant dose-volume effect relationships were demonstrated between the [Formula: see text] and [Formula: see text] and the probability of late SB morbidity. These parameters should not limit the pulsed-dose rate brachytherapy optimization process.

Vaginal dose assessment in image-guided brachytherapy for cervical cancer: Can we really rely on dose-point evaluation?

PURPOSE: Although dose-volume parameters in image-guided brachytherapy have become a standard, the use of posterior-inferior border of the pubic symphysis (PIBS) points has been recently proposed in the reporting of vaginal doses. The aim was to evaluate their pertinence. METHODS AND MATERIALS: Nineteen patients who received image-guided brachytherapy after concurrent radiochemotherapy were included. Per treatment, CT scans were performed at Days 2 and 3, with reporting of the initial dwell positions and times. Doses delivered to the PIBS points were evaluated on each plan, considering that they were representative of one-third of the treatment. The movements of the applicator according to the PIBS point were analysed. RESULTS: Mean prescribed doses at PIBS -2, PIBS, PIBS +2 were, respectively, 2.23 ± 1.4, 6.39 ± 6.6, and 31.85 ± 36.06 Gy. Significant differences were observed between the 5 patients with vaginal involvement and the remaining 14 at the level of PIBS +2 and PIBS: +47.60 Gy and +7.46 Gy, respectively (p = 0.023 and 0.03). The variations between delivered and prescribed doses at PIBS points were not significant. However, at International commission on radiation units and measurements rectovaginal point, the delivered dose was decreased by 1.43 ± 2.49 Gy from the planned dose (p = 0.019). The delivered doses at the four points were strongly correlated with the prescribed doses with R(2) ranging from 0.93 to 0.95. The movements of the applicator in regard of the PIBS point assessed with the Digital Imaging and Communications in Medicine coordinates were insignificant. CONCLUSION: The doses evaluated at PIBS points are not impacted by intrafractional movements. PIBS and PIBS +2 dose points allow distinguishing the plans of patients with vaginal infiltration. Further studies are needed to correlate these parameters with vaginal morbidity.

Pulsed-dose rate image-guided adaptive brachytherapy in cervical cancer: Dose-volume effect relationships for the rectum and bladder.

PURPOSE: To establish dose-volume effect correlations for late bladder and rectum side effects in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate image-guided adaptive brachytherapy. MATERIAL AND METHODS: The dosimetric data, converted in 2 Gy equivalent, from 217 patients were confronted to late morbidity defined as any event lasting or occurring 90 days after treatment initiation. Toxicity was assessed using the CTC-AE 3.0. Probit analyses and Log rank tests were performed to assess relationships. RESULTS: One hundred and sixty-one urinary and 58 rectal events were reported, affecting 98 (45.1%) and 51 (23.5%) patients, respectively. Cumulative incidences for grade 2-4 bladder and rectal morbidity were 24.3% and 9.6% at 3 years, respectively. Significant relationships were observed between grade 2-4 and 3-4 events and D0.1cm(3) and D2 cm(3) for the bladder and between grade 1-4 and 2-4 event probability and rectal D2 cm(3). The effective doses for 10% grade 2-4 morbidity were 65.3 Gy (59.8-81.3), and 55.4 Gy (15.7-63.6), respectively, for the rectum and bladder. Without considering urinary and rectal incontinence, for which the pertinence of correlating them with D2 cm(3) is questionable, ED10 were 68.5 Gy (62.9-110.6) and 65.5 Gy (51.4-71.6 Gy). When sorting patients according to D2 cm(3) levels, patients with high D2 cm(3) had significantly lower morbidity free survival rates for grade 1-4 and 2-4 urinary and rectal morbidity. CONCLUSION: Significant dose-volume effect relationships were demonstrated between the modern dosimetric parameters and the occurrence of late rectal and urinary morbidity in patients treated with pulsed-dose-rate brachytherapy. Further studies are required to refine these relationships according to clinical cofactors, such as comorbidities.

Adjuvant brachytherapy for endometrial cancer: advantages of the vaginal mold technique.

PURPOSE: Treatment of endometrial carcinoma in the adjuvant setting includes in most cases vaginal brachytherapy. In our institution, we use the customized vaginal mold technique. Herein, we report the advantages of this personalized applicator in terms of target coverage, normal tissue preservation, the incidence of air pockets, and its potential impact on dosimetry. METHODS AND MATERIALS: A total of 15 patients receiving postoperative vaginal cuff high-dose-rate brachytherapy with the mold applicator technique were enrolled in this prospective data collection study. Patients were treated with either two or four fractions of 5 Gy prescribed to the clinical target volume, which consisted of an irradiation of the vaginal cuff and the upper third of the vagina. Target coverage; dose to organs at risk, in addition to the volume; and the dosimetric impact of air pockets surrounding the mold were evaluated. RESULTS: In 15 patients, a total of 27 air pockets were identified. The average number of air pockets per patient was 1.8 (range, 0-4), with the average total air pocket volume being 0.1 cc (range, 0.01-0.54). The average dose reduction at 5mm from the air pocket was 26% (range, 6-45%). The minimal clinical target volume coverage reported was 95% and the maximal dose received by 2 cc of the bladder, rectum, and sigmoid never exceeded 110% of the prescribed dose. CONCLUSIONS: Vaginal cuff high-dose-rate brachytherapy using the molded applicator provides personalized tailored treatment in terms of anatomical conformity. This translates into a dosimetrical advantage with smaller and fewer air pockets than reported in the literature with the use of cylinders.

D2cm³/DICRU ratio as a surrogate of bladder hotspots localizations during image-guided adaptive brachytherapy for cervical cancer: assessment and implications in late urinary morbidity analysis.

PURPOSE: To evaluate the efficiency and potential implications of the lowest dose evaluated in the maximally exposed 2cm(3) of the bladder/dose evaluated at the International Commission for Radiation Units and Measurements (ICRU) bladder point (D2cm(3)/DICRU) ratio as surrogate to locate the D2cm(3) in patients treated with MRI-guided adaptive brachytherapy for cervical cancer. METHODS AND MATERIALS: The D2cm(3) area of the bladder was located in 69 patients, using the Digital Imaging and Communications in Medicine coordinates of its barycenter, with respect to the ICRU bladder point. The D2cm(3)/DICRU ratio was correlated with the longitudinal coordinate of the D2cm(3). Afterward, the ratio was used in a retrospective cohort of 216 patients to evaluate its impact in dose-effect analyses for late urinary incontinence. RESULTS: The mean position of the D2cm(3) was 1.73±0.98 cm cranially, 0.59±0.65 cm backwardly, and 0.02±0.89 cm to the right of the ICRU point. It was located above the ICRU point in 95.7% of the patients. Its position was lower in patients with vaginal involvement at diagnosis (p=0.03). The D2cm(3)/DICRU ratio was correlated with the position of the D2cm(3) (R²=0.716, p<10(-6)). In speculating that a ratio greater than one would predict a D2cm(3) located above the ICRU point, the sensibility, specificity, positive, and negative predictive values were 95.2%, 100%, 100%, and 66.8%, respectively. Among the retrospective cohort, 85 patients had a ratio lower than 1.1, reflecting a D2cm(3) located in the lower bladder. In these patients, analyses showed significant dose relationship with Grade 2-4 incontinence (p=0.017), whereas no correlation was demonstrated in the remaining patients. CONCLUSIONS: The D2cm(3)/DICRU ratio is a relevant surrogate to estimate the localization of the D2cm(3). Significant dose-effect correlations for incontinence were established in patients with low values for this ratio.

Impact of treatment time and dose escalation on local control in locally advanced cervical cancer treated by chemoradiation and image-guided pulsed-dose rate adaptive brachytherapy.

PURPOSE: To report the prognostic factors for local control in patients treated for locally advanced cervical cancer with image guided pulsed-dose rate brachytherapy. MATERIALS/METHODS: Patients treated with curative intent by a combination of external beam radiotherapy and pulsed-dose rate brachytherapy were selected. Local failure was defined as any relapse in the cervix, vagina, parametria, or uterus during follow-up. Prognostic factors were selected based on log rank tests and then analyzed with a Cox model. Dose/effect correlations were performed using the probit model. RESULTS: Two hundred and twenty-five patients treated from 2006 to 2011 were included. According to the FIGO classification, 29% were stage IB, 58% stage II, 10% stage III, and 3% stage IVA; 95% received concomitant chemotherapy. Thirty patients were considered having incomplete response or local failure. Among the selected parameters, D90 for HR-CTV, D90 for IR-CTV, the overall treatment time, the TRAK, and the HR-CTV volume appeared significantly correlated with local control in univariate analysis. In multivariate analysis, overall treatment time >55days and HR-CTV volume >30cm(3) appeared as independent. The probit analysis showed significant correlations between the D90 for both CTVs, and the probability of achieving local control (p=0.008 and 0.024). The thresholds to reach to warrant a probability of 90% of local control were 85Gy to the D90 of the HR-CTV and 75Gy to 90% of the IR-CTV (in 2Gy equivalent, α/ß=10). To warrant the same local control rate, the D90 HR-CTV should be significantly increased in stage III-IV tumors, in case of HR-CTV >30cm(3), excessive treatment time, or tumor width at diagnosis >5cm (97, 92, 105, and 92Gy respectively). CONCLUSIONS: Overall treatment time and HR-CTV volume were independent prognostic factors for local control. The D90 for HR and IR CTV were significantly correlated with local control, and D90 HR-CTV should be adapted to clinical criteria.

Adaptive 3D image-guided brachytherapy: a strong argument in the debate on systematic radical hysterectomy for locally advanced cervical cancer.

PURPOSE: To evaluate the outcomes of patients with locally advanced cervical cancer treated with three-dimensional image-guided brachytherapy (IGABT) after concomitant chemoradiation (CCRT). MATERIALS AND METHODS: Data from patients treated with CCRT followed by magnetic resonance imaging-guided or computed tomography-guided pulsed-dose-rate brachytherapy, performed according to the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology guidelines, were reviewed. At first, stage I or II patients systematically underwent radical hysterectomy or were offered a randomized study evaluating hysterectomy. Then, hysterectomy was limited to salvage treatment. RESULTS: Of 163 patients identified, 27% had stage IB, 57% had stage II, 12% had stage III, and 3% had stage IVA disease. The mean dose delivered (in 2-Gy dose equivalents) to 90% of the high-risk clinical target volume was 78.1 ± 9.6 Gy, whereas the doses delivered to organs at risk were maintained under the usual thresholds. Sixty-one patients underwent a hysterectomy. Macroscopic residual disease was found in 13 cases. With a median follow-up of 36 months (range, 5-79 months), 45 patients had relapsed. The 3-year overall survival rate was 76%. Local and pelvic control rates were 92% and 86%, respectively. According to the Common Toxicity Criteria 3.0, 7.4% of patients experienced late grade 3 or 4 toxicity. Most of those had undergone postradiation radical surgery (2.9% vs. 14.8; p = .005). CONCLUSION: IGABT combined with CCRT provides excellent locoregional control rates with low treatment-related morbidity, justifying the elimination of hysterectomy in the absence of obvious residual disease. Distant metastasis remains an important first relapse and may warrant more aggressive systemic treatment.