Economic evaluation and budget-impact of accelerated partial breast irradiation (APBI) versus standard or hypofractionated whole breast irradiation (WBI) in postmenopausal women with early-stage breast cancer. Results from the French SHARE randomized trial.

PURPOSE: This economic evaluation reports the incremental cost-utility ratio and national budget impact in France of accelerated partial breast irradiation (APBI) vs standard or hypofractionated whole breast irradiation (WBI) in breast cancer patients at low risk of local recurrence. MATERIALS AND METHODS: We compared 490 women randomized to the APBI (ten fractions delivered twice daily over one week) with 488 women in the WBI arm (one fraction per day delivered five days per week over three or six weeks). We took the perspective of the French national health insurance with a three-year time horizon. The outcome was quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio was estimated and uncertainty was explored by probabilistic bootstrapping. Transportation and sick leave costs were added in a sensitivity analysis and a national budget impact analysis based on the incidence of breast cancer estimates in France performed. RESULTS: At three years, the average cost per patient was €2,549 (±1,954) in the APBI arm and €4,468 (±1,586) in the WBI arm (p-value < 0.001), radiotherapy was the main driver of the difference between the two arms. No significant difference was found in QALYs. For an average of 60,000 new cases of breast cancer diagnosed annually in France, 28,000 would be eligible for treatment with APBI. A 100% uptake of APBI would result in a yearly30 million€ cost saving. CONCLUSION: APBI for the treatment of postmenopausal women with early-stage breast cancer is cost saving, with no difference in outcome measured by QALYs.

Prognostic factors of local control and progression-free survival in AJCC stages T1 and T2 cervical cancer patients treated with adjuvant brachytherapy after chemoradiotherapy.

Purpose: We assessed prognostic factors of local control and progression-free survival (PFS) of patients treated for AJCC stages T1 and T2 cervical cancer using utero-vaginal brachytherapy after chemoradiotherapy. Material and methods: This retrospective single-institution analysis included patients who underwent brachytherapy after radiochemotherapy between 2005 and 2015 at the Institut de Cancérologie de Lorraine. Adjuvant hysterectomy was optional. A multivariate analysis of prognostic factors was carried out. Results: Of 218 patients, 81 (37.2%) were AJCC stage T1, and 137 (62.8%) were AJCC stage T2. 167 (76.6%) patients had squamous cell carcinoma, 97 (44.5%) patients had pelvic nodal disease, and 30 (13.8%) patients had para-aortic nodal disease. One hundred eighty-four patients (84.4%) underwent concomitant chemotherapy, while adjuvant surgery was performed in 91 patients (41.9%) and 42 (46.2%) patients had pathological complete response. Median follow-up was 4.2 years, and local control was reported in 87.8% (95% CI: 83.0-91.8) and 87.2% (95% CI: 82.3-91.3) of patients at 2 and 5 years, respectively. In multivariate analysis, T stage (hazard ratio [HR] = 3.65, 95% CI: 1.27-10.46, p = 0.016) was associated with local control. PFS was reported in 67.6% (95% CI: 60.9-73.4) and 57.4% (95% CI: 49.3-64.2) of patients at 2 and 5 years, respectively. In multivariate analysis, para-aortic nodal disease (HR = 2.03, 95% CI: 1.16-3.54, p = 0.012), pathological complete response (HR = 0.33, 95% CI: 0.15-0.73, p = 0.006), and intermediate-risk clinical tumor volume of > 60 cc (HR = 1.90, 95% CI: 1.22-2.98, p = 0.005) were associated with PFS. Conclusions: Lower dose brachytherapy may benefit AJCC stages T1 and T2 tumors, whereas higher doses are required for larger tumors and para-aortic nodal disease involvement, respectively. Pathological complete response should be associated with better local control and not surgery.

Acute skin toxicity of conventional fractionated versus hypofractionated radiotherapy in breast cancer patients receiving regional node irradiation: the real-life prospective multicenter HYPOBREAST cohort.

BACKGROUND: Large-scale trials have shown that hypofractionated adjuvant breast radiotherapy was as effective in terms of survival and local control as conventional fractionated radiotherapy, and acute toxicity was reduced with hypofractionated radiotherapy. However, there is a lack of data about the toxicity of breast with regional nodal irradiation (RNI). The aim of this study was to assess the effect of fractionation on radiation-related acute skin toxicity in patients receiving RNI in addition to whole-breast or chest wall irradiation, using real-life data. METHODS: We conducted a prospective, multicenter cohort study with systematic computerized data collection integrated into Mosaiq®. Three comprehensive cancer centers used a standardized form to prospectively collect patient characteristics, treatment characteristics and toxicity. RESULTS: Between November 2016 and January 2022, 1727 patients were assessed; 1419 (82.2%) and 308 (17.8%) patients respectively received conventional fractionated and hypofractionated radiation therapy. Overall, the incidence of acute grade 2 or higher dermatitis was 28.4% (490 patients). Incidence was lower with hypofractionated than with conventional fractioned radiation therapy (odds ratio (OR) 0.34 [0.29;0.41]). Two prognostic factors were found to increase the risk of acute dermatitis, namely 3D (vs IMRT) and breast irradiation (vs chest wall). CONCLUSION: Using real-life data from unselected patients with regional nodal irradiation, our findings confirm the decreased risk of dermatitis previously reported with hypofractionated radiation therapy in clinical trials. Expansion of systematic data collection systems to include additional centers as well as dosimetric data is warranted to further evaluate the short- and long-term effects of fractionation in real life.

Impact of radiation therapy on fatigue at 1 year in breast cancer survivors in the prospective multicentre CANcer TOxicity cohort.

BACKGROUND: Fatigue is a common and disabling symptom after breast cancer (BC) treatment, significantly impacting patients' quality of life. We aimed to assess the impact of radiation therapy (RT) modalities on fatigue one year after treatment among patients with early-stage BC. METHODS: We used CANTO-RT, a subcohort of CANcer TOxicity (CANTO; NCT01993498), a multicentric nationwide prospective cohort of stages I-III BC treated from 2012 to 2017. Our primary outcome was severe global fatigue 1 year after RT completion (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 score ≥40/100). The secondary outcomes included severe physical, emotional and cognitive fatigue (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-FA12). RT-related variables were used as independent variables. Multivariable logistic regression models assessed associations between RT-related variables and fatigue. RESULTS: The final analytic cohort included 3295 patients. The prevalence of severe global fatigue 1 year after treatment was 33.3%. Internal mammary chain RT (adjusted odds ratio [OR] 1.48 [95% confidence interval [CI] 1.03-2.13; p = 0.0355]) and normofractionated RT (adjusted OR 1.88 [95% CI 1.06-3.31; p = 0.0298]) were associated with increased odds of severe global fatigue. In addition, there was a significant association between normofractionated RT (adjusted OR 1.849 [95% CI 1.04-3.3; p = 0.0354]) and an increased likelihood of severe physical fatigue. CONCLUSION: We found a significant association between internal mammary chain RT (versus No), normofractionated RT (versus hypofractionated RT) and increased likelihood of persistent severe global fatigue. Our data add to the current understanding of treatment-related factors affecting fatigue after BC and could lead to personalised interventions to improve the prevention and management of this disabling symptom.

A NGS-based Blood Test For the Diagnosis of Invasive HPV-associated Carcinomas with Extensive Viral Genomic Characterization.

PURPOSE: Use of circulating tumor DNA (ctDNA) for diagnosis is limited regarding the low number of target molecules in early-stage tumors. Human papillomavirus (HPV)-associated carcinomas represent a privileged model using circulating viral DNA (ctHPV DNA) as a tumor marker. However, the plurality of HPV genotypes represents a challenge. The next-generation sequencing (NGS)-based CaptHPV approach is able to characterize any HPV DNA sequence. To assess the ability of this method to establish the diagnosis of HPV-associated cancer via a blood sample, we analyzed ctHPV DNA in HPV-positive or HPV-negative carcinomas. EXPERIMENTAL DESIGN: Patients (135) from France and Senegal with carcinoma developed in the uterine cervix (74), oropharynx (25), oral cavity (19), anus (12), and vulva (5) were prospectively registered. Matched tumor tissue and blood samples (10 mL) were taken before treatment and independently analyzed using the CaptHPV method. RESULTS: HPV prevalence in tumors was 60.0% (81/135; 15 different genotypes). Viral analysis of plasmas compared with tumors was available for 134 patients. In the group of 80 patients with HPV-positive tumors, 77 were also positive in plasma (sensitivity 95.0%); in the group of 54 patients with HPV-negative tumors, one was positive in plasma (specificity 98.1%). In most cases, the complete HPV pattern observed in tumors could be established from the analysis of ctHPV DNA. CONCLUSIONS: In patients with carcinoma associated with any HPV genotype, a complete viral genome characterization can be obtained via the analysis of a standard blood sample. This should favor the development of noninvasive diagnostic tests providing the identification of personalized tumor markers. See related commentary by Rostami et al., p. 5158.

Identification of Specific Tumor Markers in Vulvar Carcinoma Through Extensive Human Papillomavirus DNA Characterization Using Next Generation Sequencing Method.

OBJECTIVES: A subset of vulvar carcinomas (VC) are associated with human papillomavirus (HPV) DNA. This trait can be used to identify tumor markers for patient's follow-up. A large diversity of HPV prevalence in VC has been reported, but no data are available concerning the insertional HPV status in this tumor type. Therefore, we have used an innovative next generation sequencing (NGS)-based CaptHPV method able to provide an extensive characterization of HPV DNA in tumors. MATERIAL AND METHODS: Tumor tissue specimens from 55 patients with VC were analyzed using p16 immunohistochemistry, in situ hybridization, polymerase chain reaction, and CaptHPV-NGS assays. RESULTS: Our analyses showed that 8 (14.5%) of 55 cases were associated with HPV 16 DNA. No other HPV genotypes were identified. The HPV genome was in a free episomal state only in one case and both episomal and integrated into the tumor cell genome in 7. There was a single insertion in 5 cases and multiple sites, scattered at different chromosomal loci in two. ISH data suggest that some of these might reflect tumor heterogeneity. Viral integration targeted cellular genes among which were TP63, CCDC148, LOC100133091, PKP1, and POLA2. Viral integration at the PKP1 locus was associated with partial gene deletion, and no PKP1 protein was detected in tumor tissue. CONCLUSIONS: Using the NGS-based innovative capture-HPV approach, we established a cartography of HPV 16 DNA in 8 VC cases and identified novel genes targeted by integration that may be used as specific tumor markers. In addition, we established a rationale strategy for optimal characterization of HPV status in VC.

Minichromosome maintenance complex component 6 (MCM6) expression correlates with histological grade and survival in endometrioid endometrial adenocarcinoma.

Minichromosome maintenance complex component 6 (MCM6) is involved in initiating DNA replication and is upregulated during licensed G0 phase of the cell cycle. This early expression permits its labeling of more proliferating cells than those by Ki-67. Here using a cohort of 89 endometrioid adenocarcinoma, we report findings made on the prognostic value of MCM6 based on immunohistochemical labeling index (LI) of the protein in comparison with that of Ki67 as no such information is currently available. Additionally, we examined the prognostic values of these markers based on their mRNA expression using a cohort of uterine corpus endometrial carcinoma (UCEC, n = 307) taken from The Cancer Genome Atlas (TCGA) database. Our evidence indicated the presence of a positive correlation between the LI of MCM6 and the histological grade of endometrioid endometrial adenocarcinoma (grade I, 66.7%; grade II, 75.3%; grade III, 81.4%; p < 0.001) and an inverse correlation between the LI of MCM6 and the overall and progression-free survival (p = 0.02 for both). The LI of Ki-67 correlated with grade (p < 0.001), but not survival. The MCM6 and Ki-67 inter-observer intra-class correlation coefficients were excellent: 0.84 (95% confidence interval, 0.83-0.91) and 0.84 (0.77-0.90), respectively. For in silico analyses of the TCGA cohort, both univariate and multivariate Cox analyses (p = 0.003 and p = 0.03, respectively) revealed high MCM6 mRNA Z-scores associated with reduced overall survival. This association was absent for Ki-67. MCM6 is thus a highly reproducible marker of poor prognosis in endometrial cancer. Evaluation of MCM6 should thus be considered in daily practice for risk stratification.

Expression of neurotensin receptor 1 in endometrial adenocarcinoma is correlated with histological grade and clinical outcome.

The promalignant effects of neurotensin (NTS) are sustained in many solid tumors, including hormone-dependent cancers. As the endometrium is also subjected to hormonal regulation, we evaluated the contribution of NTS to endometrial carcinogenesis. Neurotensin receptor 1 (NTSR1) expression and NTSR1 promoter methylation (HM450) were analyzed in 385 cases of endometrial carcinoma from The Cancer Genome Atlas (TCGA). Additionally, from a series of 100 endometrial carcinomas, and 66 benign endometrium samples, NTS and NTSR1 labeling was evaluated by immunohistochemistry. Using TCGA series, NTSR1 messenger RNA (mRNA) level was negatively correlated with overall survival (OS) and progression-free survival (PFS) (p = 0.0012 and p = 0.0116, respectively), and positively correlated with the grade (p = 0.0008). When including only endometrioid carcinomas, NTSR1 mRNA level continued to be negatively correlated with OS (log-rank: p < 0.0001) and PFS (log-rank: p = 0.002). A higher NTSR1 mRNA level was significantly associated with a loss of NTSR1 promoter methylation. Immunohistochemical expression of NTS and NTSR1 was significantly increased in adenocarcinoma (n = 100), as compared to benign endometrium (p < 0.001). NTSR1 expression was positively correlated with grade (p = 0.004). High immunohistochemical expression of cytoplasmic NTSR1 was significantly correlated with a shorter OS and PFS (p < 0.001 and p = 0.001, respectively). This correlation remained significant when excluding non-endometrioid subtypes (p = 0.04 and p = 0.02, respectively). In multivariate analysis, the expression of NTSR1 was an independent prognostic factor (p = 0.004). NTSR1 overexpression is a poor prognostic factor in endometrial cancer, highlighting the contribution of NTS in endometrial cancer progression and its uses as a prognostic marker, and as a potential therapeutic target.

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

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of dosimetric parameters on local control for patients treated with three-dimensional pulsed dose-rate brachytherapy for cervical cancer.

PURPOSE: To investigate the impact of dose-volume histograms parameters on local control of three-dimensional (3D) image-based pulsed dose-rate brachytherapy (BT). METHODS AND MATERIALS: Within a French multicentric prospective study, the data of the 110 patients treated for cervical cancer with external beam radiotherapy followed by 3D image-based and optimized pulsed dose-rate BT were analyzed. Delineation procedures were performed on magnetic resonance imaging in a minority of cases and on CT for the majority of cases, adapted from the Gynaecological Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology recommendations. Optimization procedure was left to the discretion of the treating center. RESULTS: At 2 years, local control rate reached 78%. Dose to Point A, total reference air kerma, and intermediate-risk clinical target volume (IR-CTV) V60 were predictive factors for local control (p = 0.001, p = 0.001, and p = 0.013, respectively). Patients with IR-CTV V60 <75% had a relative risk of local recurrence of 3.8 (95% confidence interval, 1.4-11.1). There was no correlation found between the high-risk clinical target volume dosimetric parameters and local control. CONCLUSIONS: This multicentric study has shown that 3D image-based BT provides a high local control rate for cervical cancer patients. The V60 for IR-CTV was identified as an important predictive factor for local control.

Impact of dosimetric and clinical parameters on clinical side effects in cervix cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy.

BACKGROUND AND PURPOSE: To assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy. MATERIALS AND METHODS: Three hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc)) volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU)) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2). RESULTS: The median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gy(α)(/)(ß)(3). In Group 2 a significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary toxicity was found using as cutoff 141, 91 and 67Gy(α)(/)(ß)(3), but not for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on urinary toxicity. CONCLUSIONS: For patients treated with brachytherapy and EBRT, rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary toxicity.

Impact of 3D image-based PDR brachytherapy on outcome of patients treated for cervix carcinoma in France: results of the French STIC prospective study.

PURPOSE: In 2005 a French multicentric non randomized prospective study was initiated to compare two groups of patients treated for cervix carcinoma according to brachytherapy (BT) method: 2D vs 3D dosimetry. The BT dosimetric planning method was chosen for each patient in each center according to the availability of the technique. This study describes the results for 705 out of 801 patients available for analysis. PATIENTS AND METHODS: For the 2D arm, dosimetry was planned on orthogonal X-Rays using low dose rate (LDR) or pulsed dose rate (PDR) BT. For the 3D arm, dosimetry was planned on 3D imaging (mainly CT) and performed with PDR BT. Each center could follow the dosimetric method they were used to, according to the chosen radioelement and applicator. Manual or graphical optimization was allowed. PATIENTS AND METHODS: Three treatment regimens were defined: Group 1: BT followed by surgery; 165 patients (2D arm: 76; 3D arm: 89); Group 2: EBRT (+chemotherapy), BT, then surgery; 305 patients (2D arm: 142; 3D arm: 163); Group 3: EBRT (+chemotherapy), then BT; 235 patients, (2D arm: 118; 3D arm: 117). PATIENTS AND METHODS: The DVH parameters for CTVs (High Risk CTV and Intermediate Risk CTV) and organs at risk (OARs) were computed as recommended by GYN GEC ESTRO guidelines. Total doses were converted to equivalent doses in 2Gy fractions (EQD2). Side effects were prospectively assessed using the CTCAEv3.0. RESULTS: The 2D and 3D arms were well balanced with regard to age, FIGO stage, histology, EBRT dose and chemotherapy. For each treatment regimen, BT doses and volumes were comparable between the 2D and 3D arms in terms of dose to point A, isodose 60 Gy volume, dose to ICRU rectal points, and TRAK. RESULTS: Dosimetric data in the 3D arm showed that the dose delivered to 90% of the High Risk CTV (HR CTV D90) was respectively, 81.2Gy(α/ß10), 63.2Gy(α/ß10) and 73.1Gy(α/ß10) for groups 1, 2 and 3. The Intermediate Risk (IR) CTV D90 was respectively, 58.5Gy(α/ß10), 57.3Gy(α/ß10) and 61.7Gy(α/ß10) for groups 1, 2 and 3. For the OARs, doses delivered to D2cc ranged 60-70Gy(α/ß3) for the bladder, 33-61Gy(α/ß3) for the rectum, and 44-58Gy(α/ß3) for the sigmoid according to the regimen. RESULTS: At 24 months, local relapse-free survival was 91.9% and 100% in group 1, 84.7% and 93% in group 2, 73.9% and 78.5% in group 3; grade 3-4 toxicity rate was 14.6% and 8.9% in group 1, 12.5% and 8.8% in group 2, and 22.7% and 2.6% in group 3 for 2D and 3D arm. CONCLUSION: This multicentric study has shown that 3D BT is feasible and safe in routine practice. It has improved local control with half the toxicity observed with 2D dosimetry. The combined treatment with radiotherapy and surgery was more toxic than definitive radiotherapy. For patients with advanced tumors, it is necessary to improve coverage of target volumes without raising toxicity.

Radiotherapy for solitary extramedullary plasmacytoma in the head-and-neck region: A dose greater than 45 Gy to the target volume improves the local control.

PURPOSE: Our aim was to determine the dose to the clinical target volume (CTV) required for solitary extramedullary plasmacytoma (EMP) in the head and neck (HN). METHODS AND MATERIALS: Seventeen patients (15 Stage I and 2 Stage II) were treated for HN EMP at our institution between 1979 and 2003. The mean International Commission on Radiation Units (ICRU) dose prescribed to the CTV was 52.6 Gy (range, 40-65 Gy) over 24 fractions (range: 20-30). The Stage II patients received neck irradiation doses of 40 and 60 Gy. A mean dose of 36.4 Gy was used for 5 Stage I patients who received elective neck irradiation. Dose administrated to the CTV was evaluated from dosimetric data or from planning films when dosimetric data were not available. Two groups of patients were distinguished: CTV covered with a dose greater than 40 Gy and CTV covered with a dose greater than 45 Gy. RESULTS: The 5-year local control was 72.8%. It was 100% for patients who received dose to the CTV > or = [DOSAGE ERROR CORRECTED] 45 Gy vs. 50% for dose to the CTV <45 Gy (p = 0.034). The prognostic factor for 5-year disease-specific survival (81.6%) was local control (p = 0.058). The prognostic factors for disease-free survival (64.1%) were monoclonal immunoglobulin secretion (p = 0.008) and a CTV dose > or = 45 Gy (p = 0.056) CONCLUSIONS: Local control of EMP in the HN seems to be improved when the dose to the CTV is > or = [DOSAGE ERROR CORRECTED] 45 Gy. A minimum dose of 45 Gy should be recommended to the CTV.

Influence of dose point and inverse optimization on interstitial cervical and oropharyngeal carcinoma brachytherapy.

BACKGROUND AND PURPOSE: Evaluation of the use of optimization methods in interstitial cervical and oropharyngeal brachytherapy; evaluation of the conformal index (COIN) and the natural dose ratio (NDR) to quantify the implant quality. MATERIAL AND METHODS: CT-based dose distributions were obtained for seven implants according to the Paris system. CT-based implants were used to assess the dose point and inverse optimization methods. To compare the results of these planning methods, the coverage index (CI), normal tissue irradiation (NTI), and the protection of organs at risk (OARs) were evaluated using cumulative dose volume histograms (CDVH). RESULTS: In regular cervical implants, a CI of 94 and 96%; a NTI of 35 and 28% resulted for non-optimized and optimized implants, respectively. In irregular cervical implants, a CI of 88, 96, and 90%; a NTI of 44, 37, and 44% resulted for non-optimized, dose point optimized, and inverse optimized implants, respectively. Compared to the non-optimized implants; both optimization methods resulted in better protection for the bladder wall. As for the protection of the rectal wall, only the inverse optimization gave a better result. In oropharyngeal implants, a better CI resulted after dose point optimization. Irradiation of the contralateral parotid were improved after both optimization methods. The maximum change in COIN that could have been achieved by optimization was 3%, as CI and NTI increased similarly. For the same value of COIN, an underdosage of PTV was avoided by the optimization methods as NDR increased from 0.86 to 1.01. CONCLUSION: CT-based optimized implant allows conformation of the dose distribution to the PTV while sparing normal tissue and organs at risk. COIN and NDR should be used together to evaluate both doses to normal tissue and organs at risk, and an under- or overdose inside the PTV.

Analysis of interaction between number of implant catheters and dose-volume histograms in prostate high- dose-rate brachytherapy using a computer model.

PURPOSE: In prostate high-dose-rate brachytherapy, to determine before implant, using the standard geometric optimization algorithm, whether there is an optimal number of catheters. MATERIALS AND METHODS: Transrectal ultrasound images of the prostate from 24 patients were transferred into the brachytherapy planning system. Urethra and prostate contours were digitized onto each axial slice of a CT scan, as well as hypothetical locations of the catheters (2/3 of the catheters along the prostate contour, 1/3 around the urethra). Each prostate was implanted with 9, 12, 15, 18, and 21 catheters. Dosimetry was optimized using a geometric optimization algorithm; prescription isodose was chosen so that 95% of planning target volume was covered by the 100% isodose. RESULTS: A significant increase in mean volume of prostate receiving 150% of the dose (V150) when the number of catheters decreased (p < 0.0001). The 9-catheter group significantly differed from each of the other groups; no difference was seen in V150 among the 21-, 18-, and 15-catheter groups. Parallel results were observed for urethra V150 and homogeneity index; there was no difference in conformity index by catheter group. CONCLUSION: V150 increased when fewer catheters were used. There was no significant difference among the 21-, 18-, and 15-catheter groups: the geometric optimization routine probably compensated for the larger distance between dwell positions. Based on the technique described in our study, we conclude that 15 to 21 catheters seem to cover the prostate adequately without creating excess hot spots.

Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centers' experience.

PURPOSE: To assess the long-term outcome for women with ductal carcinoma in situ of the breast treated in current clinical practice by conservative surgery with or without definitive breast irradiation. METHODS AND MATERIALS: We analyzed 705 cases of ductal carcinoma in situ treated between 1985 and 1995 in nine French regional cancer centers; 515 underwent conservative surgery and radiotherapy (CS+RT) and 190 CS alone. The median follow-up was 7 years. RESULTS: The 7-year crude local recurrence (LR) rate was 12.6% (95% confidence interval [CI] 9.4-15.8) and 32.4% (95% CI 25-39.7) for the CS+RT and CS groups, respectively (p <0.0001). The respective 10-year results were 18.2% (95% CI 13.3-23) and 43.8% (95% CI 30-57.7). A total of 125 LRs occurred, 66 and 59 in the CS+RT and CS groups, respectively. Invasive or microinvasive LRs occurred in 60.6% and 52% of the cases in the same respective groups. The median time to LR development was 55 and 41 months. Nine (1.7%) and 6 (3.1%) nodal recurrences occurred in the CS+RT and CS groups, respectively. Distant metastases occurred in 1.4% and 3% of the respective groups. Patient age and excision quality (final margin status) were both significantly associated with LR risk in the CS+RT group: the LR rate was 29%, 13%, and 8% among women aged < or =40, 41-60, and > or =61 years (p <0.001). Even in the case of complete excision, we observed a 24% rate of LR (6 of 25) in women <40 years. Patients with negative, positive, or uncertain margins had a 7-year crude LR rate of 9.7%, 25.2%, and 12.2%, respectively (p = 0.008). RT reduced the LR rate in all subgroups, especially in those with comedocarcinoma (17% vs. 59% in the CS+RT and CS groups, respectively, p <0.0001) and mixed cribriform/papillary tumors (9% vs. 31%, p <0.0001). In the multivariate Cox regression model, young age and positive margins remained significant in the CS+RT group (p = 0.00012 and p = 0.016). Finally, the relative LR risk in the CS+RT group compared with the CS group was 0.35 (95% CI 0.25-0.51, p = 0.0001). Subsequent contralateral breast cancer occurred in 7.1% and 7.5% of the patients in the CS+RT and CS groups, respectively. CONCLUSION: Despite the absence of randomization, our results are extremely consistent with the updated National Surgical Adjuvant Breast Project B17 and European Organization for Research and Treatment of Cancer 10853 trials. We also noted that the LR risk was very high in women <40 years and/or in the case of incomplete excision.