The Influence of Surgical Complexity and Center Experience on Postoperative Morbidity After Minimally Invasive Surgery in Gynecologic Oncology: Lessons Learned from the ROBOGYN-1004 Trial.

BACKGROUND: This study was a secondary analysis of the ROBOGYN-1004 trial conducted between 2010 and 2015. The study aimed to identify factors that affect postoperative morbidity after either robot-assisted laparoscopy (RL) or conventional laparoscopy (CL) in gynecologic oncology. METHODS: The study used two-level logistic regression analyses to evaluate the prognostic and predictive value of patient, surgery, and center characteristics in predicting severe postoperative morbidity 6 months after surgery. RESULTS: This analysis included 368 patients. Severe morbidity occurred in 49 (28 %) of 176 patients who underwent RL versus 41 (21 %) of 192 patients who underwent CL (p = 0.15). In the multivariate analysis, after adjustment for the treatment group (RL vs CL), the risk of severe morbidity increased significantly for patients who had poorer performance status, with an odds ratio (OR) of 1.62 for the 1-point difference in the WHO performance score (95 % CI 1.06-2.47; p = 0.027) and according to the type of surgery (p < 0.001). A focus on complex surgical acts showed significant more morbidity in the RL group than in the CL group at the less experienced centers (OR, 3.31; 95 % CI 1.0-11; p = 0.05) compared with no impact at the experienced centers (OR, 0.87; 95 % CI 0.38-1.99; p = 0.75). CONCLUSION: The findings suggest that the center's experience may have an impact on the risk of morbidity for patients undergoing complex robot-assisted surgical procedures.

Stereotactic body radiotherapy as a viable treatment on extracranial oligometastases in melanoma patients: a retrospective multicentric study.

Introduction: Stereotactic radiotherapy (SBRT) potentially has a role in the management of oligometastatic melanoma. However, literature with data specific to this management is very limited. The objectives of this study were to evaluate the time to local control (LC) of extra-cranial melanoma metastases after SBRT treatment and to help establish if SBRT is a useful therapy for oligometastatic melanoma. Methods: A retrospective study was conducted with data collected from two referral centers in France between 2007 and 2020. The oligometastatic status of patients was reported based on the latest recommendations with a maximum of three lesions prior to treatment. Results: A total of 69 patients receiving SBRT for 88 oligometastatic melanoma metastases were included. The median follow-up time was 42.6 months. Most patients were treated for metachronous oligometastatic lesions. Occurrence of oligoprogression, oligorecurrence, and oligopersistence was reported in 42.0%, 39.1%, and 17.4% of cases, respectively. Treated lesions were mostly pulmonary (40.6%), followed by lymph node (34.8%) and hepatic sites (24.6%). Progression-free survival at 1, 2, and 3 years were 47.0% (35-59), 27.0% (16-39), and 25.0% (15.0-37.0), respectively. Time to LC rates at 1, 2, and 3 years were 94.2% (87.0-98.1), 90.3% (81.3-96.1), and 90.3% (81.3-96.1), respectively. Overall survival at 1, 2, and 3 years were 87% (76.0-93.0), 74.0% (76.0-93.0), and 61.0% (47.0-73.0), respectively. Only 17.4% of patients experienced acute, grade 1 or grade 2 toxicities with no reports of grade 3 or higher toxicities. Conclusion: SBRT demonstrated efficacy in managing melanoma patients with extracranial oligometastases and showed an overall low toxicity profile. Future randomized studies are needed to establish the role of SBRT in therapeutic approaches for patients with oligometastatic melanoma.

Stereotactic reirradiation in the treatment of head and neck cancers: A retrospective study on the long-term experience of the Oscar Lambret Center.

BACKGROUND AND PURPOSE: Stereotactic radiotherapy potentially treats unresectable recurrences of previously irradiated head and neck (H&N) cancer. This study aimed to assess its efficacy and safety and evaluate prognostic factors. MATERIALS AND METHODS: We conducted a large retrospective series that included 110 patients who had undergone 36-Gy, six-fraction stereotactic reirradiation (CyberKnife®) for recurrent/secondary H&N cancer between 2007 and 2020 at the Oscar Lambret Center. Patient characteristics and toxicities were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. RESULTS: Median follow-up time was 106.3 months. The 2-year OS rate was 43.8 % (95 % confidence interval, 95 % CI, 34.3-52.9) and the median survival was 20.8 months (95 % CI, 16.5-26.3). The cumulative 2-year local-recurrence, regional-recurrence, and distant-metastasis rates were 52.2 % (95 % CI, 42.4-61.1 %), 12.8 % (95 % CI, 7.4-19.8 %), and 11 % (95 % CI, 6.0-17.6 %), respectively. 73 patients received concomitant cetuximab, and it was not significantly beneficial (HR = 1.34; 95 % CI, 0.80-2.26; p = 0.26). The cumulative incidences of grade ≥ 2 late toxicity was 42 % (CI95%: 33-51) at 24 months. Two grade 4 bleedings and no treatment-related deaths were reported. CONCLUSION: In a large retrospective series of SBRT reirradiation for recurrent or second primary H&N cancers, we observed a median OS of 20.8 months, with a cumulative incidence of grade ≥ 2 late toxicity of 42 % at 24 months. Such a treatment is feasible. However, local recurrence rates remain non-negligible, warranting further research. Radiosensitizer use is currently under study. Therefore, establishing a balance between therapeutic modifications and toxicity is essential.

Phase II study of 131 I-metaiodobenzylguanidine with 5 days of topotecan for refractory or relapsed neuroblastoma: Results of the French study MIITOP.

PURPOSE: We report the results of the French multicentric phase II study MIITOP (NCT00960739), which evaluated tandem infusions of 131 I-metaiodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory metastatic neuroblastoma (NBL). METHODS: Patients received 131 I-mIBG on day 1, with intravenous topotecan daily on days 1-5. A second activity of 131 I-mIBG was given on day 21 to deliver a whole-body radiation dose of 4 Gy, combined with a second course of topotecan on days 21-25. Peripheral blood stem cells were infused on day 31. RESULTS: Thirty patients were enrolled from November 2008 to June 2015. Median age at diagnosis was 5.5 years (2-20). Twenty-one had very high-risk NBL (VHR-NBL), that is, stage 4 NBL at diagnosis or at relapse, with insufficient response (i.e., less than a partial response of metastases and more than three mIBG spots) after induction chemotherapy; nine had progressive metastatic relapse. Median Curie score at inclusion was 6 (1-26). Median number of prior lines of treatment was 3 (1-7). Objective response rate was 13% (95% confidence interval [CI]: 4-31) for the whole population, 19% for VHR-NBL, and 0% for progressive relapses. Immediate tolerance was good, with nonhematologic toxicity limited to grade-2 nausea/vomiting in eight patients. Two-year event-free survival was 17% (95% CI: 6-32). Among the 16 patients with VHR-NBL who had not received prior myeloablative busulfan-melphalan consolidation, 13 had at least stable disease after MIITOP; 11 subsequently received busulfan-melphalan; four of them were alive (median follow-up: 7 years). CONCLUSION: MIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan.

Results of a 20 Year Retrospective Analysis of Early-Stage Cervical Cancer: Should 3 cm Be Considered the New Ariadne's Thread in Early Cervical Cancer Treatment?

(1) This study aims to evaluate the overall survival (OS) and recurrence-free survivals (RFS) and assess disease recurrence of early-stage cervical cancer (ESCC) patients treated with minimally invasive surgery (MIS). (2) This single-center retrospective analysis was performed between January 1999 and December 2018, including all patients managed with MIS for ESCC. (3) All 239 patients included in the study underwent pelvic lymphadenectomy followed by radical hysterectomy without the use of an intrauterine manipulator. Preoperative brachytherapy was performed in 125 patients with tumors measuring 2 to 4 cm. The 5-year OS and RFS rates were 92% and 86.9%, respectively. Multivariate analysis found two significant factors associated with recurrence: previous conization with HR = 0.21, p = 0.01, and tumor size > 3 cm with HR = 2.26, p = 0.031. Out of the 33 cases of disease recurrence, we witnessed 22 disease-related deaths. Recurrence rates were 7.5%, 12.9%, and 24.1% for tumors measuring ≤ 2 cm, 2 to 3 cm, and > 3 cm, respectively. Tumors ≤ 2 cm were mostly associated with local recurrences. Tumors > 2 cm were frequently associated with common iliac or presacral lymph node recurrences. (4) MIS may still be considered for tumors ≤ 2 cm subject to first conization followed by surgery with the Schautheim procedure and extended pelvic lymphadenectomy. Due to the increased rate of recurrence, a more aggressive approach might be considered for tumors > 3 cm.

Palpable Nodules After Autologous Fat Grafting in Breast Cancer Patients: Incidence and Impact on Follow-up.

INTRODUCTION: Autologous fat grafting (AFG) is a promising breast reconstruction technique, following surgery. However, fat necrosis after AFG can cause palpable nodules, inducing anxiety and prompting additional investigations. We aimed to determine the occurrence rate and to identify the risk factors of palpable nodules in breast cancer patients prompting complementary explorations. MATERIALS AND METHODS: We retrospectively reviewed the computerized files of consecutive breast cancer patients who underwent AFG after mastectomy or breast conservative treatment (BCT) at our center from January 2013 to December 2016. We collected data regarding palpable nodule incidences and suspicious breast imaging findings that led to additional explorations. RESULTS: Of the 252 patients reviewed, 222 (88%) underwent AFG for breast reconstruction, while 30 (12%) underwent AFG for correction of defects after BCT. The follow-up period ranged from 0 to 74 months (median: 27 months), and 201 patients had follow-ups beyond 1 year. Of the 252 patients, 66 (26.2%) underwent at least one control imaging and 24 (10%) underwent a biopsy, including 6 (2.4%) locoregional recurrence. Sixty patients (24%) were diagnosed with nodules during follow-ups. Among them, 52 (87%) patients had additional imaging, and 17 patients (28%) had a biopsy, including 82% benign histology. Patients with BCT had significantly more palpable nodules at 1 year than patients who underwent total mastectomy (odds ratio = 2.50, 95% confidence interval: 1.04. 6.03, p = 0.04). CONCLUSION: This study underlines the importance of preoperative patient information. This intervention and its follow-up should be reserved for experienced teams to limit unnecessary additional explorations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Ergonomic Assessment of the Surgeon's Physical Workload During Robot-Assisted Versus Standard Laparoscopy in a French Multicenter Randomized Trial (ROBOGYN-1004 Trial).

BACKGROUND: Standard laparoscopy (SL) is responsible for musculoskeletal disorders in surgeons because of poor ergonomic positions, which could be reduced by robot-assisted laparoscopy (RAL) owing to the surgeons' seated position. One of the aims of the ROBOGYN-1004 study (NCT01247779) was to evaluate surgeons' workloads during real-time procedures of gynecological oncological surgery. METHODS: Patients with gynecological cancer eligible for minimally invasive surgery were recruited from 13 French centers between December 2010 and December 2015. Physical workload was evaluated using the Borg scale every hour over the surgery duration and the perception of workload evaluated using NASA-TLX at the end of surgery. RESULTS: A total of 369 patients were recruited, of whom 176 underwent RAL and 193 underwent SL (per-protocol analysis). Posture during SL was significantly more challenging for all body parts except the back. There was an increase in discomfort over time (up to 4 h) for the hands and arms, neck, and legs in SL compared with RAL. Perceived physical activity and abilities were rated higher in SL than in RAL (p < 0.01), whereas perceived personal performance was higher in SL (p < 0.01). Perceived physical effort during surgery was lower in RAL than in SL. CONCLUSIONS: RAL improves the perception of physical workload. Compared with SL, the perceived effort is lower in RAL regardless of the complexity of the surgery.

Stereotactic Body Radiation Therapy for the Management of Hepatocellular Carcinoma: Efficacy and Safety.

This study aimed to describe patient characteristics, treatment efficacy, and safety in patients with hepatocellular carcinoma (HCC) undergoing stereotactic body radiation therapy (SBRT). We retrospectively analyzed data of 318 patients with 375 HCC treated between June 2007 and December 2018. Efficacy (overall survival [OS], relapse-free survival, and local control) and acute and late toxicities were described. The median follow-up period was 70.2 months. Most patients were treated with 45 Gy in three fractions. The median (range) PTV volume was 90.7 (2.6-1067.6) cc. The local control rate at 24 and 60 months was 94% (91-97%) and 94% (91-97%), respectively. Relapse-free survival at 12, 24, and 60 months was 62% (55-67%), 29% (23-36%), and 13% (8-19%), respectively. OS at 12, 24, and 60 months was 72% (95%CI 67-77%), 44% (38-50%), and 11% (7-15%), respectively. Approximately 51% and 38% experienced acute and late toxicity, respectively. Child-Pugh score B-C, high BCLC score, portal thrombosis, high GTV volume, and higher PTV volume reported on total hepatic volume ratio were significantly associated with OS. SBRT is efficient for the management of HCC with a favorable toxicity profile. The outcome is highly related to the natural evolution of the underlying cirrhosis.

Is ovarian recovery after chemotherapy in young patients with early breast cancer influenced by controlled ovarian hyperstimulation for fertility preservation or tumor characteristics? Results of a prospective study in 126 patients.

Young individuals, aged <40 years, represent 7% of all patients with early breast cancer (EBC), most of whom receive chemotherapy. Preserving future fertility in these patients has become a major concern. This prospective study assessed ovarian function during and after chemotherapy according to patient and tumor characteristics and evaluated the outcome of controlled ovarian hyperstimulation (COH). Ovarian reserve was evaluated in terms of amenorrhea duration and by longitudinal serum anti-Müllerian hormone (AMH) level variations measured at study entry, during treatment and until 24 months thereafter. COH has been proposed for patients receiving adjuvant chemotherapy. We studied the association between clinical factors and ovarian function using Cox models and logistic regression. In this young population (age < 38 years, median = 32), 85 of 90 evaluable patients (94%) experienced chemo-induced amenorrhea, including six persistent amenorrhea and one chemotherapy-induced definitive ovarian failure. Overall, 33% of patients still had undetectable AMH values 12 months after the end of chemotherapy, although most had recovered spontaneous and regular menstrual function. No specific factor was associated with clinical or biological late ovarian dysfunction, except for age and baseline AMH value. Overall, 58 patients underwent COH. The mean number of total retrieved oocytes and metaphase II oocytes were of 11.7 and 6.9, respectively. Thus, our study confirms the importance of fertility preservation in young patients with EBC. Our findings indicate that sequential chemotherapy is associated with a higher risk of persistent amenorrhea. There was no significant association between tumor characteristics, fertility preservation or recovery of ovarian reserve.

Functional Cerebral MRI Evaluation of Integration of Breast Reconstruction into the Body Schema.

BACKGROUND: The objective of breast reconstruction (BR) is to erase the after-effects of total mastectomy by allowing patients to restore their breast shape. The aim of our study was to investigate the body map integration of different types of BR using functional magnetic resonance (fMRI). PATIENTS AND METHODS: We prospectively enrolled all women undergoing BR for breast cancer to the Remasco study (NCT02553967). Participants were categorized into four groups according to the standard of care they required: immediate BR (IBR), delayed BR (DBR), flap (autologous), or implant BR. Each patient performed sensorimotor tasks during the fMRI acquisition. RESULTS: Data of 38 patients were analyzed. We identified the cingulate region as the area of interest in the brain. In the case of DBR, the brain area activated during palpation of the total mastectomy scar (before BR) was different from the brain area activated during palpation of the reconstructed breast (Brodmann areas 31 versus 32). Palpation of the native breast and reconstructed breast activated the same Brodmann area 32. Comparing the brain activation signal during palpation of the native breast and the reconstructed breast did not reveal any significant difference in the overall population (P = 0.41) or in the groups: autologous (P = 0.32), implant (P = 0.10), IBR (P = 0.72), or DBR (P = 0.10). CONCLUSIONS: This experimental study allowed us to describe and understand the brain plasticity processes that accompany BR. The results suggest that the reconstructed breast is integrated into the body schema, regardless of the type of BR or the timing.

Stereotactic Body Radiation Therapy for Oligometastatic Breast Cancer: A Retrospective Multicenter Study.

INTRODUCTION: Stereotactic radiotherapy may improve the prognosis of oligometastatic patients. In the literature, there is very little data available that is specific to breast cancer. MATERIALS AND METHODS: We conducted a multicenter retrospective study. The primary objective was to estimate progression-free survival after stereotactic body radiotherapy (SBRT) using Cyberknife of breast cancer oligometastases. The secondary objectives were to estimate overall survival, local control, and toxicity. The inclusion criteria were oligometastatic breast cancer with a maximum of five lesions distributed in one to three different organs, diagnosed on PET/CT and/or MRI, excluding brain metastases and oligoprogressions. This was combined with systemic medical treatment. FINDINGS: Forty-four patients were enrolled from 2007 to 2017, at three high-volume cancer centers. The patients mostly had one to two lesion(s) whose most widely represented site was bone (24 lesions or 44.4%), particularly in the spine, followed by liver (22 lesions or 40.7%), then pulmonary lesions (six lesions or 11.1%). The primary tumor expressed estrogen receptors in 33 patients (84.6%); the status was HER2+++ in 7 patients (17.9%). The median dose was 40 Gy (min-max: 15-54) prescribed at 80% isodose, the median number of sessions was three (min-max: 3-10). The median D50% was 42 Gy (min max 17-59). After a median follow-up of 3.4 years, progression-free survival (PFS) at one year, two years, and three years was 81% (95% CI: 66-90%), 58% (95% CI: 41-72%), and 45% (95% CI: 28-60%), respectively. The median PFS was 2.6 years (95% CI: 1.3 - 4.9). Overall survival at three years was 81% (95% CI: 63-90%). The local control rate at two and three years was 100%. Three patients (7.3%) experienced G2 acute toxicity, no grade ≥3 toxicity was reported. CONCLUSION: The PFS of oligometastatic breast cancer patients treated with SBRT appears long, with low toxicity. Local control is high. SBRT for oligometastases is rarely applied in breast cancer in light of the population in our study. Phase III studies are ongoing.

Use of a Biodegradable, Contrast-Filled Rectal Spacer Balloon in Intensity-Modulated Radiotherapy for Intermediate-Risk Prostate Cancer Patients: Dosimetric Gains in the BioPro-RCMI-1505 Study.

BACKGROUND/PURPOSE: Dose-escalated external beam radiotherapy (RT) is effective in the control of prostate cancer but is associated with a greater incidence of rectal adverse events. We assessed the dosimetric gain and safety profile associated with implantation of a new biodegradable rectal spacer balloon. MATERIALS/METHODS: Patients scheduled for image-guided, intensity-modulated RT for intermediate-risk prostate cancer were prospectively included in the French multicenter BioPro-RCMI-1505 study (NCT02478112). We evaluated the dosimetric gain, implantation feasibility, adverse events (AEs), and prostate-cancer-specific quality of life associated with use of the balloon spacer. RESULTS: After a scheduled review of the initial recruitment target of 50 patients by the study's independent data monitoring committee (IDMC), a total of 24 patients (including 22 with dosimetry data) were included by a single center between November 2016 and May 2018. The interventional radiologist who implanted the balloons considered that 86% of the procedures were easy. 20 of the 24 patients (83.3%) received IMRT and 4 (16.7%) received volumetric modulated arc therapy (78-80 Gy delivered in 39 fractions). The dosimetric gains associated with spacer implantation were highly significant (p<0.001) for most variables. For the rectum, the median (range) relative gain ranged from 15.4% (-9.2-47.5) for D20cc to 91.4% (36.8-100.0) for V70 Gy (%). 15 patients (62%) experienced an acute grade 1 AE, 8 (33%) experienced a late grade 1 AE, 1 (4.2%) experienced an acute grade 2 AE, and 3 experienced a late grade 2 AE. No grade 3 AEs were reported. Quality of life was good at baseline (except for sexual activity) and did not markedly worsen during RT and up to 24 months afterwards. CONCLUSION: The use of a biodegradable rectal spacer balloon is safe, effective and associated with dosimetric gains in modern RT for intermediate-risk prostate cancer.

Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft Tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer Trial.

PURPOSE: The VIT-0910 trial was conducted to evaluate efficacy and safety of the vincristine-irinotecan combination with and without temozolomide (VIT and VI, respectively) in relapsed or refractory rhabdomyosarcoma (RMS). METHODS: In this randomized European phase II trial, patients age 0.5-50 years received 21-day cycles combining vincristine (1.5 mg/m2 once a day on day 1 and day 8) and irinotecan (50 mg/m2 once a day from day 1 to day 5) with and without temozolomide (125 mg/m2 once a day from day 1 to day 5 and 150 mg/m2 once a day from cycle 2), until progression or unacceptable toxicity. The primary end point was objective response rate after two cycles. Secondary end points included best response, progression-free survival, overall survival, and adverse events. A Simon 2-stage design was initially planned to separately analyze 40 patients/arm. After amendment, the trial sample size was increased to 120 and a comparison between arms, adjusted for confounding factors, was added to the statistical plan (ClinicalTrials.gov, NCT01355445). RESULTS: Overall, 120 patients (60 per arm) were recruited in 37 European centers. The median age was 11 years (range, 0.75-45); 89% of patients had a relapsed RMS. The objective response rate was 44% (24 of 55 evaluable patients) for VIT versus 31% (18 of 58) for VI (adjusted odds ratio, 0.50; 95% CI, 0.22 to 1.12; P = .09). The VIT arm achieved significantly better overall survival (adjusted hazard ratio, 0.55; 95% CI, 0.35 to 0.84; P = .006) compared with VI, with consistent progression-free survival results (adj-hazard ratio, 0.68; 95% CI, 0.46 to 1.01; P = .059). Overall, patients experienced adverse events ≥ grade 3 more frequently with VIT than VI (98% v 78%, respectively; P = .009), including a significant excess of hematologic toxicity (81% v 61%; P = .025). CONCLUSION: The addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed RMS, with manageable increase in toxicity. VIT is considered the new standard treatment in these patients in the European paediatric Soft Tissue Sarcoma Group and will be the control arm in the next randomized trial.

Severe perioperative morbidity after robot-assisted versus conventional laparoscopy in gynecologic oncology: Results of the randomized ROBOGYN-1004 trial.

OBJECTIVE: In gynecologic oncology, minimally invasive surgery using conventional laparoscopy (CL) decreases the incidence of severe morbidity compared to open surgery. In 2005, robot-assisted laparoscopy (RL) was approved for use in gynecology in the US. This study aimed to assess whether RL is superior to CL in terms of morbidity incidence. METHODS: ROBOGYN-1004 (ClinicalTrials.gov, NCT01247779) was a multicenter, phase III, superiority randomized trial that compared RL and CL in patients with gynecologic cancer requiring minimally invasive surgery. Patients were recruited between 2010 and 2015. The primary endpoint was incidence of severe perioperative morbidity (severe complications during or 6 months after surgery). RESULTS: Overall, 369 of 385 patients were included in the as-treated analysis: 176 and 193 underwent RL and CL, respectively. The median operating time for RL was 190 (range, 75-432) minutes and for CL was 145 (33-407) minutes (p < 0.001). The blood loss volumes for the corresponding procedures were 100 (0-2500) and 50 (0-1000) mL (p = 0.003), respectively. The overall rates of conversion to open surgery for the corresponding procedures were 7% (10/176) and 5% (10/193), respectively (p = 0.52). Severe perioperative morbidity occurred in 28% (49/176) and 21% (41/192) of patients who underwent RL and CL, respectively (p = 0.15). At a median follow-up of 25.1 months (range, 0.6-78.2), no significant differences in overall and disease-free survival were observed between the groups. CONCLUSIONS: RL was not found superior to CL with regard to the incidence of severe perioperative morbidity in patients with gynecologic cancer. In addition, RL involved a longer operating time than CL.

Curative Irradiation Treatment of Hepatocellular Carcinoma: A Multicenter Phase 2 Trial.

PURPOSE: Liver transplantation is the standard definitive treatment for nonmetastatic hepatocellular carcinoma (HCC). However, less than 5% of patients are ultimately candidates as a result of frequent comorbidities and graft shortage. The aim of this study was to evaluate stereotactic body radiation therapy (SBRT) as an ablative treatment for inoperable HCC. METHODS AND MATERIALS: A prospective phase 2 trial included newly diagnosed single HCC lesions that were without extrahepatic extension and that were deemed unsuitable for standard locoregional therapies, with a tumor size ranging from 1 to 6 cm. The SBRT dose was 45 Gy in 3 fractions. Primary endpoint was the local control of irradiated HCC at 18 months, defined by Response Evaluation Criteria in Solid Tumors. RESULTS: Forty-three patients were treated and evaluable. Median follow-up was 4.0 years (range, 1.2-4.6 years). All 43 patients had cirrhosis; 37 (88%) were Child-Pugh grade A and 5 (12%) grade B (1 missing data). No patients had received prior local treatment. Thirteen patients (31%) presented grade ≥3 acute adverse events, including 8 patients with an abnormality of the liver function tests (19%). Three patients (10%) experienced a decline in Child-Pugh at 3 months post-SBRT. The 18-month local control rate was 98% (95% confidence interval, 85%-99%). The 18-month overall survival rate was 72% (range, 56%-83%). Median overall survival was 3.5 years. CONCLUSIONS: Local control and overall survival after SBRT for untreated solitary HCC were excellent despite candidates being unfit for transplantation, resection, ablation, or embolization treatments. SBRT should be considered as a bridge to transplant or as definitive therapy for those ineligible for transplant.

Outcomes of pre-operative brachytherapy followed by hysterectomy for early cervical cancer.

OBJECTIVE: The standard of care for early cervical cancer is radical hysterectomy; however, consideration of pre-operative brachytherapy has been explored. We report our experience using pre-operative brachytherapy plus Wertheim-type hysterectomy to treat early stage cervical cancer. METHODS: This single-center study evaluated consecutive patients with histologically proven node-negative early stage cervical cancer (International Federation of Gynecology and Obstetrics 2009 stage IB1-IIB) that was treated using pre-operative brachytherapy and hysterectomy. Pre-brachytherapy staging was performed using magnetic resonance imaging (MRI) and pelvic lymph node assessment was performed using lymphadenectomy. The tumor and cervical tissues were treated using brachytherapy (total dose 60 Gy) followed by Wertheim-type hysterectomy. The study included patients from January 2000 to December 2013. RESULTS: A total of 80 patients completed a median follow-up of 6.7 years (range 5.4-8.5). The surgical specimens revealed a pathological complete response for 61 patients (76%). Patients with incomplete responses generally had less than 1 cm residual tumor at the cervix, and only one patient had lymphovascular space involvement. The estimated 5-year rates were 88% for overall survival (95% CI 78% to 94%) and 82% for disease-free survival (95% CI 71% to 89%). Toxicities were generally mild-to-moderate, including 26 cases (33%) of grade 2 late toxicity and 10 cases (13%) of grade 3 late toxicity. Univariate analyses revealed that poor disease-free survival was associated with overweight status (≥25 kg/m2, HR 3.05, 95% CI 1.20 to 7.76, p=0.019) and MRI tumor size >3 cm (HR 3.05, 95% CI 1.23 to 7.51, p=0.016). CONCLUSIONS: Pre-operative brachytherapy followed by Wertheim-type hysterectomy may be safe and effective for early stage cervical cancer, although poorer outcomes were associated with overweight status and MRI tumor size >3 cm.

Salvage Stereotactic Body Radiation Therapy for Local Prostate Cancer Recurrence After Radiation Therapy: A Retrospective Multicenter Study of the GETUG.

PURPOSE: To assess the efficacy and safety of salvage stereotactic body radiation therapy (SBRT) in patients with biopsy-proven local prostate cancer recurrence after radiation therapy. METHODS AND MATERIALS: Between April 2010 and January 2017, 100 patients were included in 7 centers. Disease extension was assessed by pelvic multiparametric magnetic resonance imaging and choline positron emission tomography in 87% and 94% of patients, respectively. The median time interval between the 2 treatments was 7.5 years (range, 2-18). Median prostate-specific antigen at recurrence was 4.3 ng/mL (range, 2-38). Median SBRT dose was 36 Gy (range, 25-36.25) in 6 fractions (range, 5-6), every other day. Thirty-four percent of patients were treated by androgen deprivation therapy for a median duration of 12 months. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03. RESULTS: Median follow-up was 29.3 months (range, 4-91). Second biochemical recurrence-free survival rate at 3 years was 55% (95% confidence interval [CI], 42%-66%). The initial D'Amico group, time interval after first radiation therapy, and SBRT dose were prognostic factors of biochemical recurrence-free survival in multivariate analysis (P = .09, P = .025, P = .018, respectively). No patient developed acute gastrointestinal toxicity of grade >1; rates of acute genitourinary toxicity of grade 2 and 3 were 8% and 1%, respectively. The actuarial 3-year grade ≥2 genitourinary and gastrointestinal toxicity was 20.8% (95% CI, 13%-29%) and 1% (95% CI, 0.1%-5.1%), respectively. One patient presented with neuritis of grade 3. CONCLUSIONS: With a short follow-up, this study shows that salvage SBRT allows for encouraging control and acceptable toxicity. Further prospective studies are necessary to confirm these preliminary results and to determine late toxicity.

Adapted strategy to tumor response in childhood nasopharyngeal carcinoma: the French experience.

PURPOSE: The aim of this study was to retrospectively study survival and long-term morbidities of children with nasopharyngeal carcinoma (NPC) treated by induction chemotherapy and concurrent chemoradiation (CRT). The total dose of radiation was adapted to the response following neoadjuvant chemotherapy. METHODS: Children with non-metastatic NPC treated in France between 1999 and 2015 were retrospectively included in the study. The strategy combined neoadjuvant platinum-based chemotherapy, followed by adapted CRT to tumor response. RESULTS: In total, 95 patients (median age 15 years [range, 7-23 years], male-to-female ratio 1.8) with undifferentiated NPC were included; 59% of patients had TNM stage IV. Intensity-modulated radiotherapy (IMRT) was delivered to 57 patients (60%), while the other patients were treated with conformal RT (3D-RT). After a median follow-up of 4.5 years [range, 3.6-5.5 years], 13 relapses and seven deaths had occurred. The 3­year overall and relapse-free survival (RFS) were 94% [95% CI, 85-97%] and 86% [77-92%], respectively. The locoregional failure rate was 6% [95% CI, 2-14]. Long-term treatment-related sequelae of grade 2+ were reported by 37 (50%) patients; odynophagia was significantly reduced treated by IMRT vs. conventional 3D-RT (7% vs. 55%, p = 0.015). Using a reduction dose of 59.4 Gy, 54 Gy, and 45 Gy, respectively, to the primary, involved, and uninvolved neck nodes, after a favorable tumor response, was not associated with an increased locoregional failure rate. CONCLUSIONS: The survival rates for NPC have been considerably improved by means of multimodal therapy, but long-term locoregional morbidity remains common. Use of IMRT may induce less residual odynophagia. Radiation dose reduction adapted to chemotherapy response does not have a negative impact on outcome. These findings support the use of an RT protocol adapted to the tumor response to neoadjuvant chemotherapy for a long-lasting improvement in the patient's quality of life.