Image-Guided Adaptive Brachytherapy (IGABT) for Primary Vaginal Cancer: Results of the International Multicenter RetroEMBRAVE Cohort Study.

PURPOSE: This study assessed outcomes following the nowadays standing treatment for primary vaginal cancer with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT) in a multicenter patient cohort. METHODS: Patients treated with computer tomography (CT)-MRI-assisted-based IGABT were included. Retrospective data collection included patient, tumor and treatment characteristics. Late morbidity was assessed by using the CTCAE 3.0 scale. RESULTS: Five European centers included 148 consecutive patients, with a median age of 63 years. At a median follow-up of 29 months (IQR 25-57), two- and five-year local control were 86% and 83%; disease-free survival (DFS) was 73% and 66%, and overall survival (OS) was 79% and 68%, respectively. Crude incidences of ≥ grade-three urogenital, gastro-intestinal and vaginal morbidity was 8%, 3% and 8%, respectively. Lymph node metastasis was an independent prognostic factor for disease-free survival (DFS). Univariate analysis showed improved local control in patients with T2-T4 tumors if >80 Gy EQD2α/ß10 was delivered to the clinical target volume (CTV) at the time of brachytherapy. CONCLUSIONS: In this large retrospective multicenter study, IGABT for primary vaginal cancer resulted in a high local control with acceptable morbidity. These results compared favorably with two-dimensional (2D) radiograph-based brachytherapy and illustrate that IGABT plays an important role in the treatment of vaginal cancer.

Repeated courses of low-dose 2 × 2 Gy radiation therapy in patients with indolent B-cell non-Hodgkin lymphomas.

PURPOSE: In patients with indolent B-cell non-Hodgkin's lymphoma (B-NHL), one course of low-dose radiotherapy (LD-RT) 2 × 2 Gy is emerging as new option of therapy in palliative setting. Efficacy of LD-RT when repeated remains to be determinate. This study aims to assess the efficacy of repeated LD-RT given in patients with indolent B-NHL. MATERIALS AND METHODS: All consecutive adult patients who received two or more courses of LD-RT 2 × 2 Gy for indolent B-NHL at Gustave Roussy institution, during the period 1990-2015 were retrospectively investigated. RESULTS: Thirty-three patients received two or more courses of LD-RT for indolent B-NHL during the study period. The median age was 57 (range 37-80) years, histological types were distributed among follicular lymphoma (n = 24 pts; 73%), marginal-zone lymphoma (n = 6 pts; 18%), and primary cutaneous follicle center lymphoma (n = 3 pts; 9%). The median number of low-dose radiation therapy courses given per patients was 2 (range 2-6). The overall response rates following the first and the second course of LD-RT were 96% and 88%, respectively (P = .31). The 1- and 2-years local control rates following the first courses of LD-RT were 94% (CI 95: 86-100) and 94% (CI 95: 86-98); and were 91% (CI 95: 82-100) and 88% (CI 95: 77-100) following the second course of LD-RT (P = .39). CONCLUSION: The repeated courses of LD-RT offered similar efficacy compare with the first course in patients with indolent B-NHL. LD-RT repeated is a simple, easy to give, and non-toxic asset that could be investigated as treatment option in patients with indolent B-NHL.

Recommendations from gynaecological (GYN) GEC-ESTRO working group - ACROP: Target concept for image guided adaptive brachytherapy in primary vaginal cancer.

BACKGROUND AND AIM: External beam radiotherapy (EBRT) combined with brachytherapy has an essential role in the curative treatment of primary vaginal cancer. EBRT is associated with significant tumour shrinkage, making primary vaginal cancer suitable for image guided adaptive brachytherapy (IGABT). The aim of these recommendations is to introduce an adaptive target volume concept for IGABT of primary vaginal cancer. METHODS: In December 2013, a task group was initiated within GYN GEC-ESTRO with the purpose to introduce an IGABT target concept for primary vaginal cancer. All participants have broad experience in IGABT and vaginal cancer brachytherapy. The target concept was elaborated as consensus agreement based on an iterative process including target delineation and dose planning comparison, retrospective analysis of clinical data and expert opinions. RESULTS: Gynaecological examination and MR imaging are the modalities of choice for local tumour assessment. A specific template for standardised documentation with clinical drawings for vaginal cancer was developed. The adaptive target volume concept comprises different response-related target volumes. For EBRT these are related to the primary tumour and the lymph nodes, while for IGABT these are related to the primary tumour and are consisting of the residual gross tumour volume (GTV-Tres) and the high-, and intermediate risk clinical target volumes (CTV-THR, CTV-TIR). CONCLUSION: This target concept for IGABT of primary vaginal cancer defines adaptive target volumes for volumetric dose prescription and should improve comparability of different radiotherapy schedules of this rare disease. A prospective evaluation of the target volume concept within a multicentre study is planned.

Bowel morbidity following radiochemotherapy and image-guided adaptive brachytherapy for cervical cancer: Physician- and patient reported outcome from the EMBRACE study.

BACKGROUND/PURPOSE: This study describes late bowel morbidity prospectively assessed in the multi-institutional EMBRACE study on MRI-guided adaptive brachytherapy in locally advanced cervical cancer (LACC). MATERIALS/METHODS: A total of 1176 patients were analyzed. Physician reported morbidity (CTCAE v.3.0) and patient reported outcome (PRO) (EORTC QLQ C30/CX24) were assessed at baseline and at regular follow-up. RESULTS: At 3/5 years the actuarial incidence of bowel morbidity grade 3-4 was 5.0%/5.9%, including incidence of stenosis/stricture/fistula of 2.0%/2.6%. Grade 1-2 morbidity was pronounced with prevalence rates of 28-33% during follow-up. Diarrhea and flatulence were most frequently reported, significantly increased after 3 months and remained elevated during follow-up. Incontinence gradually worsened with time. PRO revealed high prevalence rates. Diarrhea ≥"a little" increased from 26% to 37% at baseline to 3 months and remained elevated, difficulty in controlling bowel increased from 11% to 26% at baseline to 3 months gradually worsening with time. Constipation and abdominal cramps improved after treatment. CONCLUSION: Bowel morbidity reported in this large cohort of LACC patients was limited regarding severe/life-threatening events. Mild-moderate diarrhea, flatulence and incontinence were prevalent after treatment with PROs indicating a considerable and clinically relevant burden. Critical knowledge based on the extent and manifestation pattern of treatment-related morbidity will serve future patient management.

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.

[Hodgkin lymphoma: Current and future therapeutic strategies]. / Le lymphome de Hodgkin : stratégies thérapeutiques actuelles et futures.

Hodgkin lymphoma (HL) is a cancer that mostly affects young people, in which modern therapeutic strategies using chemotherapy and radiotherapy result in a cure rate exceeding 80%. Survivors are exposed to long-term consequences of treatments, such as secondary malignancies and cardiovascular diseases, whose mortality exceeds the one of the disease itself, with long-term follow-up. The current therapeutic strategy in HL, based on the assessment of initial risk factors, is the result of large clinical trials led by the main international cooperating groups. More recently, several groups have tried to develop treatment strategies adapted to the response to chemotherapy, evaluated by interim PET/CT scan. However to date, the combined treatment with chemotherapy followed by radiation therapy remains a standard in most of the above-diaphragmatic localized forms. Immune checkpoint inhibitors, and especially anti-PD1 antibodies, have shown dramatic results in some serious forms of relapsed or refractory HL, with limited toxicity, and may contribute in the future to reduce the toxicities of treatments.

Brachytherapy Combined With Surgery for Conservative Treatment of Children With Bladder Neck and/or Prostate Rhabdomyosarcoma.

PURPOSE: To report the results of a conservative strategy based on partial surgery combined with brachytherapy in a prospective cohort of children with bladder-prostate rhabdomyosarcoma (BP RMS). METHODS AND MATERIALS: We prospectively documented the outcome of children treated in our department between 1991 and 2015 for BP RMS and undergoing a multimodal approach combining conservative surgery (partial cystectomy and/or partial prostatectomy) and perioperative interstitial low-dose-rate or pulse-dose-rate brachytherapy. Before brachytherapy, children had received chemotherapy with modalities depending on their risk group of treatment. RESULTS: A total of 100 patients were identified, with a median age of 28 months (range, 5.6 months-14 years). According to the Intergroup Rhabdomyosarcoma Study (IRS) group, 84 were IRS-III, and 12 were IRS-IV tumors. Four patients were treated at relapse. The median number of chemotherapy cycles before local therapy was 6 (range, 4-13). After surgery, 63 patients had a macroscopic tumor residuum. Five patients underwent a brachytherapy boost before pelvic external beam radiation therapy because of nodal involvement, and 95 had exclusive brachytherapy. Median follow-up was 64 months (range, 6 months-24.5 years). Five-year disease-free and overall survival rates were 84% (95% confidence interval 80%-88%) and 91% (95% confidence interval 87%-95%), respectively. At last follow-up most survivors presented with only mild to moderate genitourinary sequelae and a normal diurnal urinary continence. Five patients required a secondary total cystectomy: 3 for a nonfunctional bladder and 2 for relapse. CONCLUSION: Brachytherapy is effective as part of a conservative strategy for BP RMS, with a relatively low delayed toxicity as compared with previously published studies using external beam radiation therapy. Longer follow-up is required to ensure that the functional results are maintained over time.

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.

Assessment of the novel online delineation workshop dummy run approach using FALCON within a European multicentre trial in cervical cancer (RAIDs).

BACKGROUND AND PURPOSE: Online delineation workshops (ODW) permit training of geographically dispersed participants. The purpose is to evaluate the methodology of an ODW using FALCON to harmonize delineation within a European multicentre trial on locally advanced cervical cancer (LACC). MATERIAL AND METHODS: Two ODW included 46 clinicians (14 centres). Clinicians completed baseline (C1), guideline (C2) and final contours (C3) for external beam radiotherapy (EBRT) and brachytherapy (BT) for LACC. Interobserver and intraobserver variability was evaluated quantitatively (using the DICE index) and qualitatively compared to expert contours. RESULTS: Nine clinicians submitted for EBRT and BT for C1-C3. Thirty-two sent any contour. Interobserver quantitative comparisons for EBRT showed significant improvement for C2 vs. C1 for bowel, CTV node, CTV-p and GTV node with significant detriment for GTV node (C3 vs. C1; C2), CTV-p (C3 vs. C2) and bowel (C3 vs. C2), showing in general an improvement in C2 vs. C1, with a detriment in C3 vs. C2 for two target volumes and an organ at risk. For BT there was significant improvement for C2 vs. C1 for bladder, GTV, HR-CTV and IR-CTV, with significant detriment for bladder (C3 vs. C2), thus overall improvement in C2 vs. C1, with only a detriment in C3 vs. C2 for bladder. Centres using MRI imaging for BT contouring did significantly better in the BT case for HR-CTV than those which used other techniques (C2 vs. C1: p<0.005; C3 vs. C1: p=0.02). Intraobserver quantitative comparisons showed significant improvement contouring a region of interest between C2 vs. C1, C3 vs. C1 and C3 vs. C2 for EBRT and between C2 and C1 for BT. CONCLUSIONS: ODW offer training, initial contouring harmonization and allow assessment of centres.

Locally advanced cervical cancer: Is it relevant to report image-guided adaptive brachytherapy using point A dose?

PURPOSE: To evaluate the usefulness of reporting the point A dose in patients with locally advanced cervical cancer treated with image-guided adaptive brachytherapy (IGABT). METHODS AND MATERIALS: Dosimetric data from patients treated with a combination of chemoradiation and intracavitary IGABT were examined in light of their outcomes. Prescribing followed the Groupe Européen de Curiethérapie-European Society for Radiation Oncology recommendations. All doses were converted in 2-Gy equivalent. The relationships between the D90 high-risk clinical target volume (CTVHR) and intermediate-risk clinical target volume (CTVIR) and point A doses were studied. Dose-effect relationships based on the probit model and log-rank test were assessed. RESULTS: Two hundred twelve patients were included with a median followup of 53.0 months. A total of 28 local relapses were reported, resulting in a local control rate of 86.6% at 3 years. Mean D90 CTVHR, CTVIR, and point A doses were: 79.7 ± 10.4 Gy, 67.4 ± 5.8 Gy, and 66.4 ± 5.6 Gy, respectively. The mean D90 were significantly different and independent from the mean point A dose, even in bulky tumors at diagnosis or in large CTVHR lesions. Point A dose appeared correlated with TRAK, and finally with the D90 CTVHR through a complex formula including the CTVHR volume (R2 = 0.55). Whereas significant relationships between the probability of achieving local control and the D90 CTVHR and CTVIR (p = 0.08 and 0.025) were observed, no similar relationship was found with point A dose except a trend of an inverse relation. After sorting patients according to three dose levels, highest local control rates were observed in patients with D90 CTVHR ≥85 Gy, whereas those with point A doses ≥70 Gy had the worst outcomes. CONCLUSIONS: In patients treated with IGABT, point A dose is not predictive of local control but a surrogate of the irradiated volume. Its relationships with the D90 CTVHR are indirect and complex rising the question of relevance of its reporting in routine.

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.

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.

Contribution of image-guided adaptive brachytherapy to pelvic nodes treatment in locally advanced cervical cancer.

PURPOSE: With the increasing use of simultaneous integrated boost in the treatment of cervical cancer, there is a need to anticipate the brachytherapy (BT) contribution at the level of the pathologic pelvic lymph nodes. This study aimed to report the dose delivered at their level during BT. METHODS AND MATERIALS: Patients with pelvic nodal involvement and treated with a combination of chemoradiation followed by image-guided adaptive pulsed-dose-rate BT were selected. On per BT three-dimensional images, pelvic lymphadenopathies were delineated, without planning aim. For the purposes of the study, D100, D98, D90, and D50 were reviewed and converted in 2-Gy equivalent doses, using the linear quadratic model with an α/ß of 10 Gy. RESULTS: Ninety-one patients were identified, allowing evaluation at the level of 226 lymphadenopathies. The majority of them were external iliac (48%), followed by common iliac (25%), and internal iliac (16%) regions. The 2-Gy equivalent doses D98 were 4.4 ± 1.9 Gy, 5.4 ± 3.1 Gy, and 4.3 ± 2.1 Gy for the obturator, internal iliac, and external iliac, respectively, and 2.8 ± 2.5 Gy for the common iliac. The contribution to the common iliac nodes was significantly lower than the one of external and internal iliac (p < 0.001). CONCLUSIONS: BT significantly contributes to the treatment of pelvic nodes at the level of approximately 5 Gy in the internal, external, and obturator areas and 2.5 Gy in the common iliac, allowing the anticipation of nodal boost with the simultaneous integrated boost technique. However, important individual variations have been observed, and evaluation of the genuine BT contribution should be recommended.

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.

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.

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.

Post radiation hysterectomy in locally advanced cervical cancer: Outcomes and dosimetric impact.

PURPOSES: Firstly, to evaluate the impact of completion hysterectomy after chemoradiation and image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. Secondly, to assess a potential differential dose-effect relationship for the rectum and bladder according to the realization of hysterectomy. MATERIAL AND METHODS: Two cohorts of patients were identified, differing by the realization of completion hysterectomy. Inclusions were limited to FIGO stage I-II, with no para-aortic involvement. All patients received a combination of pelvic chemoradiation followed by IGABT. Their outcomes and morbidity were reviewed. Log-rank tests were used to compare survivals. Probit analyses were performed to study dose-volume effect relationships. RESULTS: The two cohorts comprised 54 patients in the completion surgery group and 157 patients in the definitive radiotherapy group. They were well balanced, except for the mean follow-up, significantly longer in the post hysterectomy cohort and the use of PET-CT in the work-up, more frequent in the definitive radiotherapy cohort. Although less local relapses were reported in the hysterectomy group, the 5-year disease-free and overall survival did not differ between groups. The cumulative incidence of severe late morbidity was significantly increased in the hysterectomy cohort: 22.5% versus 6.5% at 5years (p=0.016). Dose-volume effects were observed for the bladder, with the D2cm3 corresponding with a 10% probability of late severe morbidity urinary events (ED10) of 67.8Gy and 91.9Gy in the hysterectomy and definitive radiotherapy cohorts, respectively. A D90 CTVHR of 85Gy (planning aim) corresponded with a 93.3% rate of local control in the definitive radiotherapy cohort whereas it corresponded with a 77.3% chance to have a good histologic response (complete response or microscopic residual disease) in the hysterectomy group. CONCLUSION: No benefit from completion hysterectomy in terms of overall or disease-free survival rates was observed, which was moreover responsible for an increase of the severe late morbidity. The realization of post-radiation hysterectomy resulted in a shift of the ED10 of 24.1Gy.

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.