Preclinical ex vivo evaluation of the diagnostic performance of a new device for in situ label-free fluorescence spectral analysis of breast masses.

OBJECTIVES: To assess the diagnostic performance of a new device for in situ label-free fluorescence spectral analysis of breast masses in freshly removed surgical specimens, in preparation for its clinical development. METHODS: Sixty-four breast masses from consenting patients who had undergone either a lumpectomy or a mastectomy were included. Label-free fluorescence spectral acquisitions were obtained with a 25G fibre-containing needle inserted into the mass. Data from benign and malignant masses were compared to establish the most discriminating thresholds and measurement algorithms. Accuracy was verified using the bootstrap method. RESULTS: The final histological examination revealed 44 invasive carcinomas and 20 benign lesions. The maximum intensity of fluorescence signal was discriminant between benign and malignant masses (p < .0001) whatever their sizes. Statistical analysis indicated that choosing five random measurements per mass was the best compromise to obtain high sensitivity and high negative predictive value with the fewest measurements. Thus, malignant tumours were identified with a mean sensitivity, specificity, negative and positive predictive value of 98.8%, 85.4%, 97.2% and 93.5%, respectively. CONCLUSION: This new in situ tissue autofluorescence evaluation device allows accurate discrimination between benign and malignant breast masses and deserves clinical development. KEY POINTS: • A new device allows in situ label-free fluorescence analysis of ex vivo breast masses • Maximum fluorescence intensity discriminates benign from malignant masses (p < .0001) • Five random measurements allow a high negative predictive value (97.2%).

Optimizing Local Control in High-Grade Uterine Sarcoma: Adjuvant Vaginal Vault Brachytherapy as Part of a Multimodal Treatment.

PURPOSE: The phase III European Organization for Research and Treatment of Cancer 55874 study has shown that external beam radiotherapy (EBRT) given as adjuvant treatment decreased locoregional recurrences from 40% to 20% in patients (pts) with localized uterine sarcomas (US). No data exist, however, on the place of brachytherapy (BT). MATERIAL AND METHODS: We conducted a single-center retrospective analysis of pts receiving adjuvant BT of the vaginal vault based on the vaginal mold technique as part of their multimodal adjuvant treatment for a high-grade US from 1985 to 2015. Treatment characteristics, patterns of relapse, and toxicity were examined. RESULTS: Median follow-up time was 5.5 years. A total of 98 pts with high-grade US were identified: 81 leiomyosarcomas and 17 undifferentiated sarcomas. Postoperative chemotherapy was delivered in 53 pts. Median dose of EBRT was 45 Gy in 25 fractions. High-dose rate, low-dose rate, and pulsed-dose rate techniques were used in 66, 31, and 1 pts, respectively. At last follow-up, six pts (6.1%) experienced a locoregional relapse as first event. The International Federation of Gynecology and Obstetrics stage and the tumor size were associated with a higher probability of local relapse. When focusing on pts with stage I-III disease, 5-year overall survival was 77% (95% confidence interval: 67%-87%) and 5-year survival without locoregional failure was 91% (83%-98%). Toxicities were mild to moderate, with only four acute grade 3 toxicities and two grade 3 late effects. CONCLUSION: Vaginal vault BT as part of a multimodal adjuvant treatment was associated with a high locoregional control rate and with acceptable side effects in localized high-grade US. The Oncologist 2017;22:182-188Implications for Practice: This study suggests that an aggressive adjuvant treatment combining chemotherapy and pelvic external beam radiotherapy followed with a brachytherapy of the vaginal vault is associated with a high locoregional control rate and an acceptable toxicity rate in patients with high grade uterine sarcoma. Adding a brachytherapy boost could also allow deescalating the total dose of pelvic external beam radiotherapy, in order to decrease the side effects of adjuvant treatment in these patients without increasing the risk of local relapse. However, the prognosis remains determined by a high frequency of systemic relapses.

Outcome of early stage cervical cancer patients treated according to a radiosurgical approach: Clinical results and prognostic factors.

OBJECTIVE: To report clinical results of a multimodal strategy based on preoperative brachytherapy followed with surgery in early stage cervical cancer. MATERIALS/METHODS: The outcome of consecutive patients receiving brachytherapy in our Institution for an early stage IB1-IIA1 invasive cervical cancer with risk factors (lymphovascular embols and/or tumor >2cm) between 2000 and 2013 was analyzed. The treatment consisted of preoperative low dose or pulse dose-rate utero-vaginal brachytherapy followed, 6-8weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic±para-aortic lymph node dissection. A postoperative chemoradiation was delivered in patients with histological evidence of lymph nodes metastases. RESULTS: 182 patients were identified. Histological examination of hysterectomy specimen showed the presence of a tumor residuum in 55 patients (30.2%). One patient (0.5%) had residual tumor cells in the parametria. With a median follow-up of 5.3years, 14 patients (7.7%) presented tumor relapse, including three (1.6%) local relapses. Five-year disease-free survival (DFS) rate was 93.6% (95%CI: 91.6-95.6%). In log-rank analysis, presence of pelvic nodal metastases at time of lymphadenectomy (p=0.001) and tumor size ≥3cm (p=0.003) correlated with a poorer DFS. Presence of a tumor residuum on hysterectomy specimen correlated with a higher risk of pelvic or para-aortic failure (p=0.035). A time interval>10weeks between brachytherapy and surgery correlated with a higher risk of failure outside the pelvis (p=0.003). Significant postoperative complications were reported in 16 patients (8.8%). All delayed toxicities were mild to moderate. CONCLUSIONS: A preoperative brachytherapy is a safe and effective option in early stage cervical cancer.

Clinical outcomes of definitive chemoradiation followed by intracavitary pulsed-dose rate image-guided adaptive brachytherapy in locally advanced cervical cancer.

OBJECTIVE: To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided adaptive brachytherapy (IGABT). METHODS: Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/- para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations. RESULTS: Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage≥IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4+/-10.3Gy and 67.7+/-6.1Gy. After a median follow-up of 38.8months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p=0.06). Local control rates at 3years were 95.6% in the group of patients with D90 of HR-CTV≥85Gy, 88.8% in those with D90 between 80 and 85Gy, and 80% when D90<80Gy (p=0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%. CONCLUSIONS: CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases.

Long-term evaluation of urinary, sexual, and quality of life outcomes after brachytherapy for penile carcinoma.

PURPOSE: Brachytherapy (BT) is an effective organ-preserving treatment for selected localized penile carcinoma, providing high local control rates. Long-term functional results however, are still insufficiently evaluated. METHODS AND MATERIALS: All consecutive patients treated with low-dose-rate or pulse-dose-rate BT in our institute for a localized penile cancer and who were in first complete remission and followed for at least 3 years were included. A self-reporting questionnaire was sent, to assess: 1/urinary function, 2/sexual function, 3/cosmetic aspect of the penis, and 4/quality of life. RESULTS: Thirty-nine patients fulfilled inclusion criteria and were sent the questionnaire. Twenty-three patients (59%) answered. Median age was 63.4 years, (interquartile range [IR]: 49.7-67.0). Median followup was 5.9 years (IR: 5.2-6.7). The urinary scores showed moderate lower urinary tract symptoms. During the followup, a urethral dilation or self-catheterization had been necessary in 30% and 13%, respectively. Sixteen (70%) patients continued to maintain a sexual activity and the erectile dysfunction was mild. Finally, quality of life was good with a median score of 80/100 (IR = 65-90) and was only impacted by pain (p = 0.02). Overall, 57% and 39% declared having none or moderate pain/discomfort, respectively. CONCLUSIONS: Although this questionnaire needs to be validated in an independent cohort, our results show the moderate impact of BT on functional outcomes, confirming that it is an adequate first-intent organ-sparing strategy in patients with localized penile carcinoma.

Brachytherapy for conservative treatment of invasive penile carcinoma in older patients: Single institution experience.

BACKGROUND: No study has examined the possibility to perform an organ sparing strategy in older patients with penile carcinoma, and amputation is frequently proposed. We report our experience of interstitial brachytherapy for the conservative treatment of penile carcinoma confined to the glans in patients aged of 70years and more. METHODS: A total of 55 patients candidates to conservative brachytherapy were identified. Median age was 73.8years (range: 70-95years). Patients underwent a circumcision then 3-4weeks later, an interstitial brachytherapy was delivered, median dose of 65Gy (range 55-74Gy). Salvage surgery was discussed in patients with histological confirmation of residual/relapsed tumor. RESULTS: With median follow-up of 9.0years, eight patients (14.5%) experienced a relapse, including five patients with local relapse. Three patients with local relapse only underwent salvage penile surgery, including two partial glansectomies and one total penectomy, and were in second complete remission at last follow-up. Among 55 patients analyzed for late side effects, seven patients (13.0%) presented pain or ulceration, 12 (22.2%) experienced urethral or meatal stenosis requiring at least one dilatation, two patients (3.7%) experienced both ulcerations and urethral complication. Three patients (5.5%) needed partial glansectomy for focal necrosis. At five years, estimated overall survival rate was 74.5% (95%CI: 62.0-87.0%) and local relapse free rate was 91.0% (95%CI: 82.6-99.4%). CONCLUSION: Brachytherapy is feasible in selected older patients with penile carcinoma, with efficacy and toxicity rates comparable to that of other series in younger patients.

Helping patients make informed decisions. Two-year evaluation of the Gustave Roussy prostate cancer multidisciplinary clinic.

OBJECTIVES: The initial treatment decision for newly diagnosed non-metastatic prostate cancer is complex. Multiple valid approaches exist, without a clear and absolute consensus for every clinical scenario, and therefore specialist opinions may vary. Multidisciplinary consultations focusing on shared decision-making aim to provide an apposite tool for the initial treatment decision. We have evaluated the first two years of activity of the Gustave Roussy Prostate Cancer Multidisciplinary Clinic (PCMC), dedicated to the initial decision-making for non-metastatic prostate cancer. METHODS: PCMC consists of two consecutive specialist consultations with a urological surgeon and a radiation oncologist, followed by a dedicated Tumor Board discussion. A study questionnaire was addressed to all PCMC patients via postal mail. Medical notes and questionnaire responses of 195 eligible patients were analyzed. RESULTS: The questionnaire response rate was 69% (134 patients). Complete satisfaction rate was high (114 of 118 responders, 97%). Patients were offered new treatment options in 55% of cases, and felt better informed in 98% (122 of 125 responders). The double consultation was considered useful (124 of 129 responders, 96%). Reported feeling of active participation was significantly elevated (117 of 131 responders, 89%), while 46% of patients (57 of 125) modified their decision on the management of their prostate cancer following their PCMC consultation. CONCLUSIONS: The experience of a multidisciplinary consultation in the initial management of non-metastatic prostate cancer renders high patient satisfaction, improves their appreciation of feeling better informed, promotes active participation and shared decision-making and strongly influences their final decision.

Locally advanced cervical cancer with bladder invasion: clinical outcomes and predictive factors for vesicovaginal fistulae.

OBJECTIVE: We report outcomes of cervical cancer patients with bladder invasion (CCBI) at diagnosis, with focus on the incidence and predictive factors of vesicovaginal fistula (VVF). RESULTS: Seventy-one patients were identified. Twenty-one (30%) had para-aortic nodal involvement. Eight had VVF at diagnosis. With a mean follow-up time of 34.2 months (range: 1.9 months-14.8 years), among 63 patients without VVF at diagnosis, 15 (24%) developed VVF. A VVF occurred in 19% of patients without local relapses (9/48) and 40% of patients with local relapse (6/15). Two-year overall survival (OS), disease-free survival (DFS) and local control rates were 56.4% (95% CI: 44.1-67.9%), 39.1% (95% CI: 28.1-51.4%) and 63.8% (95% CI: 50.4-75.4%), respectively. Para-aortic nodes were associated with poorer OS (adjusted HR = 3.78, P-value = 0.001). In multivariate analysis, anterior tumor necrosis on baseline MRI was associated with VVF formation (63% vs 0% at 1 year, adjusted-HR = 34.13, 95% CI: 4.07-286, P-value = 0.001), as well as the height of the bladder wall involvement of >26 mm (adjusted-HR = 5.08, 95% CI: 1.38-18.64, P-value = 0.014). CONCLUSIONS: A curative intent strategy including brachytherapy is feasible in patients with CCBI, with VVF occurrence in 24% of the patients. MRI patterns help predicting VVF occurrence. METHODS: Patients with locally advanced CCBI treated with (chemo)radiation ± brachytherapy in our institute from 1989 to 2015 were analyzed. Reviews of baseline magnetic resonance imaging (MRI) scans were carried out blind to clinical data, retrieving potential parameters correlated to VVF formation (including necrosis and tumor volume).

Stereotactic radiation therapy in the strategy of treatment of metastatic renal cell carcinoma: A study of the Getug group.

BACKGROUND: Renal cell carcinoma (RCC) is usually considered radioresistant, but stereotactic radiation therapy (SRT) may increase local disease control. This study aimed to assess the benefit of SRT in the management of metastatic RCC patients. METHODS: Data of all RCC patients who received SRT between 2008 and 2015 with curative intent were retrospectively collected in six French referral centres. Local control (LC), progression-free survival (PFS), local recurrence-free survival (LRFS), time to systemic therapy (TTS) and overall survival (OS) were assessed. RESULTS: One hundred and eighty-eight patients treated with SRT for 252 RCC metastases (brain [n = 120]; spine [n = 75]; and others [n = 57]) were recensed. SRT was performed for oligoprogressive disease (101 patients), oligometastatic disease (80 patients) or residual tumour after a partial response to systemic treatment (7 patients). The median biologically effective dose was 78 Gy. For the whole population, local control rates at 6, 12 and 24 months were 87.5%, 82.9% and 77.6%, respectively; median PFS, LRFS, TTS and OS were 8.5, 23.2, 13.2 and 29.2 months, respectively. Among patients treated for oligoprogressive/oligometastatic disease, the median PFS, TTS, and OS were 8.6/7.6, 10.5/14.2 and 23.2/33.9 months, respectively. Among the 7 patients treated with SRT after partial response to systemic treatment, no relapse occurred for 3 of them after a median follow-up of 22 months. Acute and late severe toxicities were noted in 5 (2.6%) patients. CONCLUSIONS: SRT is effective and safe for oligometastatic and oligoprogressive RCC patients and may delay introduction or change of systemic therapy.

[Clinical trials and perspectives of radiotherapy for uterine endometrial cancers]. / Essais et nouvelles perspectives dans la radiothérapie des cancers de l'endomètre.

The adjuvant management of uterine endometrial cancer has been studied in many randomized trials, leading to define postoperative therapeutic indications, depending on the risk factors for relapse, and on the expected benefit in terms of locoregional control and survival. The potential toxicity of treatments should be also considered. We review the available literature that yielded to guidelines that were recently published, on behalf of European societies, and we highlight the perspectives on ongoing studies, aimed at better defining the place and type of adjuvant treatment.

Inflammatory bowel diseases activity in patients undergoing pelvic radiation therapy.

BACKGROUND: Few studies with contradictory results have been published on the safety of pelvic radiation therapy (RT) in patients with inflammatory bowel disease (IBD). METHODS: From 1989 to 2015, a single center retrospective analysis was performed including all IBD patients who received pelvic external beam radiation therapy (EBRT) or brachytherapy (BT) for a pelvic malignancy. Treatment characteristics, IBD activity and gastrointestinal (GI) toxicity were examined. RESULTS: Overall, 28 patients with Crohn's disease (CD) (n=13) or ulcerative colitis (n=15) were included in the present study. Median follow-up time after irradiation was 5.9 years. Regarding IBD activity, only one and two patients experienced a severe episode within and after 6 months of follow-up, respectively. Grade 3/4 acute GI toxicity occurred in 3 (11%) patients, whereas one (3.6%) patient experienced late grade 3/4 GI toxicity. Only patients with rectal IBD location (P=0.016) or low body mass index (BMI) (P=0.012) experienced more severe IBD activity within or after 6 months following RT, respectively. CONCLUSIONS: We report an acceptable tolerance of RT in IBD patients with pelvic malignancies. Specifically, a low risk of uncontrolled flare-up was observed.

Brachytherapy for Conservative Treatment of Invasive Penile Carcinoma: Prognostic Factors and Long-Term Analysis of Outcome.

PURPOSE: To report the largest experience with brachytherapy as a conservative approach for the treatment of penile carcinoma. METHODS AND MATERIALS: We examined the outcomes of 201 patients treated at our institution over 45 years for invasive squamous cell carcinoma of the glans penis by brachytherapy. RESULTS: With a median follow-up of 10.7 years, local relapse as first failure was reported in 37 patients (18.9%), and 24 of 31 patients (77.4%) with local failure only were in complete remission after new treatment. At last follow-up 25 patients (12.4%) underwent partial surgery and 7 (3.5%) total penectomies for relapse. Fifty patients (24.8%) presented urethral stenosis requiring at least 1 dilatation, and 14 (7%) required limited surgeries for toxicities. At 5 years the estimated overall survival rate was 79% (95% confidence interval 73%-85%). The estimated original local control rate was 82% (95% confidence interval 76%-88%). Presence of inguinal lymph node metastasis and tumor size correlated with a poorer overall and disease-free survival in univariate and multivariate analyses. In univariate analysis, neutrophilia at diagnosis correlated with a higher probability of distant relapse (P=.025), and a dose ≥62 Gy correlated with better local control in N0 patients (P=.038). The risk of complication correlated with the dose, treated volume, and dose rate. CONCLUSION: This large institutional experience confirms the high local control achieved with brachytherapy for penile carcinoma, with the advantage of organ preservation. Most local relapses are efficiently salvaged by second-intent surgery.

Image-guided adaptive brachytherapy in cervical cancer: Patterns of relapse by brachytherapy planning parameters.

PURPOSE: Cervical cancer patients with a bulky high-risk clinical target volume (HR-CTV) get the largest benefit of dose escalation in terms of local control. However, the expected survival benefit could be lessened by a higher metastatic risk. We examined the patterns of relapse according to major prognostic factors: the HR-CTV volume and to the D90 HR-CTV. METHODS AND MATERIALS: The clinical records of patients treated with pulsed-dose-rate image-guided adaptive brachytherapy after concurrent pelvic chemoradiation were reviewed. All patients had an optimal workup before treatment comprising a 18-fluorodeoxyglucose positron emission tomography/computed tomography and a para-aortic lymph node dissection. Patients with initial extrapelvic disease were excluded. RESULTS: A total of 109 patients fulfilled inclusion criteria. Median followup was 39 months. An HR-CTV volume ≥40 cm(3) was associated with a poorer local failure-free survival. There was a strong inverse correlation between the HR-CTV volume and the D90 of the HR-CTV (correlation coefficient r = -0.696; p < 0.001) with increasing HR-CTV volume being associated with a decreasing D90 HR-CTV. A D90 HR-CTV <85 Gy and an HR-CTV volume ≥40 cm(3) were significant univariate factors for experiencing nonlocal failure (p = 0.002 and 0.035, respectively), even after exclusion of local relapses. CONCLUSION: A lower ability to reach the target D90 HR-CTV planning and an HR-CTV volume ≥ 40 cm(3) correlated with a high propensity of relapsing at distance, these factors being interrelated. Next step of treatment personalization should design strategies integrating this risk, which is now the main cause of failure.

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.

Tumor dose-volume response in image-guided adaptive brachytherapy for cervical cancer: A meta-regression analysis.

PURPOSE: Image-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose-volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series. METHODS AND MATERIALS: Eligibility was limited to series reporting dosimetric parameters according to the Groupe Européen de Curiethérapie-European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2-3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported. RESULTS: An exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p < 0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3-83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8-96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose-volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2-86.0%) local control probability. CONCLUSION: Based on published data from a high number of patients, significant dose-volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria.

Neutrophilia in locally advanced cervical cancer: A novel biomarker for image-guided adaptive brachytherapy?

OBJECTIVE: To study the prognostic value of leucocyte disorders in a prospective cohort of cervical cancer patients receiving definitive chemoradiation plus image-guided adaptive brachytherapy (IGABT). RESULTS: 113 patients were identified. All patients received a pelvic irradiation concomitant with chemotherapy, extended to the para-aortic area in 13 patients with IVB disease. Neutrophilia and leukocytosis were significant univariate prognostic factors for poorer local failure-free survival (p = 0.000 and p = 0.002, respectively), associated with tumor size, high-risk clinical target volume (HR-CTV) and anemia. No effect was shown for distant metastases but leukocytosis and neutrophila were both poor prognostic factors for in-field relapses (p = 0.003 and p < 0.001). In multivariate analysis, HR-CTV volume (p = 0.026) and neutrophils count > 7,500/µl (p = 0.018) were independent factors for poorer survival without local failure, with hazard ratio (HR) of 3.1. MATERIALS AND METHODS: We examined patients treated in our Institution between April 2009 and July 2015 by concurrent chemoradiation (45 Gy in 25 fractions +/- lymph node boosts) followed by a magnetic resonance imaging (MRI)-guided adaptive pulse-dose rate brachytherapy (15 Gy to the intermediate-risk clinical target volume). The prognostic value of pretreatment leucocyte disorders was examined. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophils count exceeding 10,000 and 7,500/µl, respectively. CONCLUSIONS: Neutrophilia is a significant prognostic factor for local relapse in locally advanced cervical cancer treated with MRI-based IGABT. This biomarker could help identifying patients with higher risk of local relapse and requiring dose escalation.

Impact of primary para-aortic lymphadenectomy on distant failure in locally advanced cervical cancer patients treated in the era of image-guided adaptive brachytherapy.

To investigate the impact of a primary para-aortic lymphadenectomy (PAL) in locally advanced cervical cancer patients receiving definitive chemoradiation, we reviewed the clinical records of consecutive patients treated in our Institution and receiving an external beam irradiation followed with an image-guided adaptive brachytherapy for a locally advanced cervical cancer. We examined the impact of performing a primary PAL as part of primary staging for guiding irradiation fields in patients without extra-pelvic PET uptake. The outcome of patients presenting para-aortic lymph node uptake (PALNU) was also examined. 186 patients were identified. Median follow-up was 44.4 months. Patients receiving a primary PAL (PAL group) and those who received upfront pelvic chemoradiation (no-PAL group) did not significantly differ for loco-regional failures. Survival without distant failure (DFFS), including para-aortic relapses, was at 3 years 87 % (95 % CI 84-90 %) in PAL group, 67 % (95 % CI 59-85 %) in the no-PAL group and 44 % (95 % CI 32-66 %) in the PALNU group (p = 0.04 for comparison between PAL and no-PAL groups). In a multivariate model including para-aortic lymphadenectomy, pelvic nodal uptake and high-risk clinical target volume as adjustment variables, a para-aortic lymphadenectomy was significant for DFS (HR = 0.47, 95 % CI 0.26-0.84, p = 0.01). Although confounding factors could account for these retrospective results, a primary PAL with tailored irradiation fields based on para-aortic histological findings seems to be associated with a better control for distant metastases. A randomized trial is testing the benefit of this strategy.

Preoperative image-guided brachytherapy in early stage cervical cancers.

OBJECTIVE: To examine the clinical results of a preoperative image-guided pulse-dose-rate brachytherapy (PDR-BT) in early stage cervical cancer. MATERIALS/METHODS: We examined the outcome of consecutive patients with early stage cervical cancer undergoing preoperative image-guided PDR-BT between 2004 and 2013 because of risk factors (lymphovascular embols and/or tumour>2cm). The objective was to deliver 60Gy to 100% of the intermediate risk clinical target volume. Brachytherapy was followed, 6-8weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic +/- para-aortic lymph node dissection. Patients with positive lymph nodes had postoperative chemoradiation. RESULTS: 77 patients met the above criteria of preoperative PDR-BT. On hysterectomy specimen, 54 (70.1%) presented a complete histological response. Four (5.2%) had a tumour residuum⩾1cm. Median follow-up was 46.8months. 5-Year disease-free survival (DFS) rate was 84.4%. Only one local recurrence was observed. The presence of lymph nodal metastases, a tumour size>3cm and a brachytherapy/surgery time interval⩾9weeks correlated with a poorer DFS. Six postoperative complications were encountered (7.8%). Total reference air kerma correlated with late vaginal toxicity (p=0.02). CONCLUSIONS: A preoperative image-guided PDR-BT was safe and effective. Predictive factors for survival and toxicity were evidenced.

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.

[Impact of radiotherapy on female fertility]. / Impact de la radiothérapie sur la fertilité féminine.

Radiation therapy may have deleterious effects on female fertility. It can cause ovarian dysfunction, uterine damages or disrupt the hypothalamic-pituitary axis. These effects occur at varying dose levels usually relatively low compared to the prescribed doses. Other co-factors influence the effects of radiation therapy on fertility, such as age or therapy with alkylating agents. This review aims to make an update on the current state of knowledge about the impact of radiotherapy on female fertility.