Dupont C., Vermandel M., Leroy H. A., Quidet M., Lecomte F., Delhem N., Mordon S., Reyns N.   INtraoperative photoDYnamic Therapy for GliOblastomas: Study Protocol for a Phase I Clinical Trial.  Neurosurgery.  2018

BACKGROUND: Glioblastoma (GBM) is characterized by marked proliferation, major infiltration, and poor prognosis. Despite current treatments, including surgery, radiation oncology, and chemotherapy, the overall median survival is 15 mo and the progression-free survival is 7 to 8 mo. Because of systematic relapse of the tumor, the improvement of local control remains an issue. In this context, photodynamic therapy (PDT) may offer a new treatment modality for GBM. OBJECTIVE: To assess the feasibility of intraoperative PDT early after surgical resection of GBM without unacceptable and unexpected toxicities. METHODS: The INDYGO clinical trial (INtraoperative photoDYnamic Therapy for GliOblastomas) treatment will be carried out in addition to the current standard of care (SOC) of glioblastoma: maximum resection surgery followed by concomitant radio-chemotherapy and adjuvant chemotherapy. PDT treatment will be delivered during surgery early, after the fluorescence-guided resection. Immunological responses and biomarkers will also be investigated during the follow-up. A total of 10 patients will be recruited during this study. EXPECTED OUTCOMES: Clinical follow-up after the SOC with PDT is expected to be similar (no significant difference) to the SOC alone. DISCUSSION: This INDYGO trial assesses the feasibility of intraoperative 5-aminolevulinic acid PDT, a novel seamless approach to treat GBM. The technology is easily embeddable within the reference treatment at a low-incremental cost. The safety of this new treatment modality is a preliminary requirement before a multicenter randomized clinical trial can be further conducted to assess local control improvement by treating infiltrating and nonresected GBM cells.

Villers A., Puech P., Flamand V., Haber G. P., Desai M. M., Crouzet S., Leroy X., Chopra S., Lemaitre L., Ouzzane A., Gill I. S.   Partial Prostatectomy for Anterior Cancer: Short-term Oncologic and Functional Outcomes.  Eur. Urol..  2017 ;72 :333-342

BACKGROUND: Focal ablative therapy may be a suboptimal option for anterior prostate cancers (APCs) reaching the prostate apex due to concerns for thermal injury to the external sphincter. OBJECTIVE: To explore the technical feasibility of anterior partial prostatectomy (APP) for isolated APCs detected by magnetic resonance imaging (MRI), and to report short-term oncologic and functional outcomes. DESIGN, SETTING, AND PARTICIPANTS: Following institutional review board approval, over an 8-yr period (2008-2015) 17 consenting patients were enrolled in a prospective single-arm single-center Innovation, Development, Exploration, Assessment, Long-term (IDEAL) phase 2a study. Inclusion criteria comprised preurethral, low- to intermediate-risk APC diagnosed by MRI, and targeted biopsies. Robotic template APP was performed; posterolateral aspect of the submontanal urethra, peripheral zone, and periprostatic tissues were preserved intact. Median follow-up was 30 mo (interquartile range [IQR]: 25-70). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We noted the incidence of perioperative complications and examined reports of pathology, prostate-specific antigen (PSA), imaging, biopsies, and questionnaires. RESULTS AND LIMITATIONS: Preoperatively, median PSA was 9.8 ng/ml, Gleason score was 6-7 (3 + 4), and cancer volume was 3.7cm(3) (IQR: 1.7-4.6). The technique was feasible in all cases. Perioperative complications included anastomotic leak (12%; G2), urinary tract infection (6%; G2), and transient intestinal ileus in one case (6%; G2). At 3 mo, continence and potency rates were 100% and 83%, respectively. Median nadir PSA was 0.4 ng/ml (IQR: 0.3-0.7). All margins and posterolateral margins rates were 55% and 35%, respectively. APC recurrence-free survival at 2 yr was 0.86 (95% confidence interval [CI], 0.55-0.96). Four patients (24%) who recurred underwent an uncomplicated completion of robot-assisted prostatectomy. Regarding limitations, CIs are quite wide for reported outcomes. CONCLUSIONS: Robotic partial prostatectomy for isolated APC is feasible with good functional results. While promising, much more research is needed to verify our initial outcomes and appropriately position APP in the treatment paradigms for APC. PATIENT SUMMARY: We explored a novel approach for partial prostatic surgical ablation for prostate cancer located in the anterior part of the prostate as an alternative to other focal ablative techniques.

Grabarz A., Azais H., Petit S., Dedet B.   Placental metastasis of breast adenocarcinoma.  Gynecol. Obstet. Fertil. Senol..  2017 ;45 :323-324
Vera P., Thureau S., Chaumet-Riffaud P., Modzelewski R., Bohn P., Vermandel M., Hapdey S., Pallardy A., Mahé M. A., Lacombe M., Boisselier P., Guillemard S., Olivier P., Beckendorf V., Salem N., Charrier N., Chajon E., Devillers A., Aide N., Danhier S., Denis F., Muratet J. P., Martin E., Berriolo-Riedinger A., Kolesnikov-Gauthier H., Dansin E., Massabeau C., Courbon F., Farcy-Jacquet M. P., Kotzki P. O., Houzard C., Mornex F., Vervueren L., Paumier A., Fernandez P., Salaun M., Dubray B.   Phase II Study of a Radiotherapy Total Dose Increase in Hypoxic Lesions Identified by F-18-Misonidazole PET/CT in Patients with Non-Small Cell Lung Carcinoma (RTEP5 Study).  J. Nucl. Med..  2017 ;58 :1045-1053

See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant (18)F-misonidazole ((18)F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The (18)F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In (18)F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral alpha = 0.05, power 1-beta = 0.95). Results: Seventy-nine patients were preincluded, 54 were included, and 34 were (18)F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the (18)F-FMISO-positive group). DFS and overall survival at 1 y were 0.86 (95% CI, 0.77-0.96) and 0.63 (95% CI, 0.49-0.74), respectively. DFS was longer in the (18)F-FMISO-negative patients (P = 0.004). The radiotherapy dose was not associated with DFS when adjusting for the (18)F-FMISO status. One toxic death (66 Gy) and 1 case of grade 4 pneumonitis (>66 Gy) were reported. Conclusion: Our approach results in a response rate of 40% or more, with acceptable toxicity. (18)F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy.

Bendifallah S., Perrin M., Ouldamer L., Lavoué V., Canlorbe G., Raimond E., Hudry D., Coutant C., Graesslin O., Touboul C., Collinet P., Daraï E., Ballester M.   Honing the classification of high-risk endometrial cancer with inclusion of lymphovascular space invasion.  Surg. Oncol.-Oxf..  2017 ;26 :1-7

OBJECTIVES: The purpose of this study was to analyse the clinical impact of LVSI status in a large French multicentre cohort of women with high-risk ECs according to the ESMO classification. METHODS: Data of 258 women with high-risk EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from prospective multicentre database. The end points were the recurrence and the lymph node metastasis (LNM) rates. Recurrence free survival (RFS) and overall survival (OS) were analyzed. RESULTS: The recurrence and LNM rates in the whole population were 32.9% and 34.5%, respectively. The median follow-up and initial recurrence times were 27 (range: 1-151) and 23.5 (range: 1-151) months, respectively. The respective 3-year RFS rates according to the LNM and LVSI status were, 78.3% (95% CI, 70.1-87.3), 53.7% (95% CI, 40.8-70.6), 65.5% (95% CI, 46.1-93.2), 43.5% (95% CI, 30.3-62.3) for women with no LN metastasis/no LVSI; no LN metastasis/LVSI present; LN metastasis/no LVSI; LN metastasis/LVSI present, respectively (p = 0.0005). CONCLUSIONS: LVSI status remains a strong prognostic factor in high-risk ECs associated with a higher recurrence rate and lower RFS and OS whatever the histological type and lymph node status. It could thus be considered in future trials to guide decision-making about adjuvant therapy in high-risk ECs.

Stabler S., Becquart C., Dumezy F., Terriou L., Mortier L.   Hemophagocytic lymphohistiocytosis in patients with metastatic malignant melanoma.  Melanoma Res..  2017 ;27 :377-379

Hemophagocytic lymphohistiocytosis (HLH) is an autoinflammatory disease that classically occurs because of infections, autoinflammatory, or autoimmune diseases, hematologic cancers, and rarely because of solid tumor. We report a rare case of HLH attributed to metastatic malignant melanoma treated without corticosteroid and with a nonfatal outcome thanks to specific therapies: etoposide for HLH and a selective inhibitor of mutated forms of BRAF kinase associated with a MEK inhibitor for melanoma.

Dadoun Y., Azaïs H., Keller L., d'Orazio E., Collinet P., Decanter C.   Systematic proposal of fertility preservation by mature oocyte cryopreservation for recurrent benign ovarian tumors.  Gynecol. Obstet. Fertil. Senol..  2017 ;45 :359-365

OBJECTIVES: To investigate prospectively the pattern of the follicular growth and to characterize the COH outcome in terms of oocyte number and maturity in patients with voluminous recurrent benign ovarian tumors with a high surgical risk of significant reduction of the ovarian follicular content. METHODS: The inclusion criteria were: age between 18 and 36, presence of at least one benign ovarian tumor (>/= 5cm) with high risk of recurrence. The fertility preservation cycle was performed at least 3 months after the cyst surgery. The controlled ovarian stimulation was performed after the ovarian reserve was assessed (AMH measurement and sonographic antral follicle count). Triggering was performed by hCG when at least 3 follicles reached 18mm of diameter. Metaphase II oocytes were cryopreserved by the vitrification technique. RESULTS: Twenty-four women with dermoid, endometrioma or seromucinous cysts were included from January 2015 to July 2016. All of them had previous ovarian surgery. Mean AMH levels were 15.3pmol/L. The mean number of total oocytes retrieved was 7+/-5. The mean number of metaphase II oocytes was 4.4+/-4. The incidence of low ovarian response was 38%. Among the patients, 86% had less than 8 metaphase II oocytes vitrified. Seven patients asked for a second cycle in order to have more oocytes. CONCLUSION: We demonstrated the feasibility of the systematic proposal of fertility preservation by oocyte cryopreservation in this group of young patients with recurrent ovarian benign tumors. Taking into account history of previous surgery and high incidence of low ovarian reserve, the ovarian response under stimulation was frequently poor with, as consequence, low retrieved oocyte number per cycle. An oocyte accumulation strategy is then proposed to enhance further pregnancy chances.

Leroy V., Templier C., Faivre J. B., Scherpereel A., Fournier C., Mortier L., Wemeau-Stervinou L.   Pembrolizumab-induced pneumonitis.  ERJ Open Res.  2017 ;3

Three cases of pembrolizumab-induced pneumonitis are described, two being consistent with organising pneumonia