Grabarz A., Azais H., Petit S., Dedet B.   Placental metastasis of breast adenocarcinoma.  Gynecol. Obstet. Fertil. Senol..  2017 ;45 :323-324
Poupon C., Bendifallah S., Ouldamer L., Canlorbe G., Raimond E., Hudry N., Coutant C., Graesslin O., Touboul C., Collinet P., Bricou A., Huchon C., Daraï E., Ballester M., Levêque J., Lavoue V.   Management and Survival of Elderly and Very Elderly Patients with Endometrial Cancer: An Age-Stratified Study of 1228 Women from the FRANCOGYN Group.  Ann. Surg. Oncol..  2017 ;24 :1667-1676

BACKGROUND: Little data exist about the clinical management and survival of elderly patients with endometrial cancer. This study aimed to evaluate the management of elderly and very elderly patients with endometrial cancer as well as the overall survival (OS) rate, disease-free survival (DFS) rate, and cancer-specific survival (CSS) rate in a multicenter cohort. METHODS: Data from 1228 patients with endometrial cancer who received primary treatment between January 2001 and December 2012 were collected from a multicenter database. Clinical management, DFS, CSS, and OS were analyzed. RESULTS: Based on the international endometrial cancer risk classification, 36% (212/582) of women age 65 years or younger, 42% (220/526) of women ages 65-80 years, and 48% (58/120) of women older than 80 years showed high-risk endometrial cancer (p < 0.001). Pelvic lymphadenectomy was performed for 85% (230/271) of the women age 65 years or younger and 46% (33/71) of the women older than 80 years (p < 0.001). Radiotherapy was performed for 27% (33/120) of the very elderly and 40% (233/582) of the young patients (p = 0.009). The 3-year CSS rates were 95% (95% confidence interval [CI], 93-97%) for the women age 65 years or younger, 90% (95% CI, 87-94%) for the women ages 65-80 years, and 82% (95% CI, 73-93%) for the women older than 80 years (p < 0.001). CONCLUSIONS: The elderly and very elderly patients with endometrial cancer showed poorer prognosis than young patients. The significant lower CSS rate for the elderly patients could have be due to both the higher rate of high-risk endometrial cancer and undertreatment. Specific guidelines for the management of elderly and very elderly patients with endometrial cancer are needed to improve their prognosis.

Vicentini C., Carpentier O., Lecomte F., Thecua E., Mortier L., Mordon S. R.   Treatment of a Vulvar Paget's Disease by Photodynamic Therapy With a New Light Emitting Fabric Based Device.  Lasers Surg. Med..  2017 ;49 :177-180

INTRODUCTION: The non-invasive vulvar Paget's disease is an intra-epidermal carcinoma with glandular characteristics. It appears like an erythematous plaque. The main symptoms are pruritus and pain. The standard treatment is surgical excision in depth. This treatment is complicated with a severe morbidity and photodynamic therapy can be an alternative choice. However, the pain experienced during the photodynamic treatment of vulvar lesion is intense and leads to a premature interruption of the treatment. The light emitting fabric is a part of a device under clinical evaluation for the treatment of actinic keratosis with photodynamic therapy. We report the observation of a vulvar Paget's disease treated by this device with a satisfactory result and an excellent tolerance. CLINICAL OBSERVATION: The patient has been diagnosed with non-invasive vulvar Paget's disease for 25 years. The disease recurred constantly despite several imiquimod applications, LASER treatments and conventional photodynamic therapy. These procedures were complicated with intense pain. To improve the tolerance, we performed three PDT sessions a month apart using a 16% methyl-aminolevulinate cream (Metvixia(R) Galderma, Lausanne, Switzerland) with the light emitting fabric at low irradiance (irradiance = 6 mW/cm(2) -fluence = 37 J/cm(2) ) with a satisfactory result and an excellent tolerance. DISCUSSION: There are no controlled trials evaluating the efficacy of photodynamic therapy in the treatment of vulvar Paget's disease. The treatment and follow-up protocols in the literature are heterogeneous. Pain is the most common side effect with greater intensity for perineal locations where photodynamic therapy is impractical outside of anesthesia or hypnosis. CONCLUSION: We report the case of a multirecidivant non-invasive vulvar Paget's disease treated with a satisfactory result and an excellent tolerance by the new light emitting fabric device. A specific study is required but the light emitting fabric could be indicated for the treatment of Paget disease of perineal location. Lasers Surg. Med. 49:177-180, 2017. (c) 2017 Wiley Periodicals, Inc.

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.

Desvignes C., Abirached H., Templier C., Drumez E., Lepesant P., Desmedt E., Mortier L.   BRAF inhibitor discontinuation and rechallenge in advanced melanoma patients with a complete initial treatment response.  Melanoma Res..  2017 ;27 :281-287

BRAF inhibitors (BRAFi), a targeted therapy, are used to treat metastatic late-stage melanomas harbouring the BRAF-V600 mutation (found in about 50% of melanomas). The targeted therapy is generally maintained until tumour progression or major toxicity occurs, although responses are often limited in time. It is unknown whether melanoma patients achieving a complete response with targeted therapy can safely discontinue treatment. We retrospectively observed the clinical course of patients with metastatic melanoma who discontinued BRAFi therapy after achieving a complete response and those with an incomplete response combined with surgical removal of the remaining tumours. We also evaluated the effectiveness of BRAFi in these patients after recurrence. In 11 patients, the best response was diagnosed after a median BRAFi treatment duration of 105 (29-341) days. The median follow-up after BRAFi initiation was 769 (435-1765) days. Recurrence was observed in all 11 patients (100%), median: 82 (27-322) days. Five patients achieved a complete response, with a median progression-free survival after cessation of 136.5 (34-322) days versus 82 (27-144) days for six patients with an incomplete response combined with surgical removal of remaining tumours. Baseline characteristics and time to best response and to discontinuation did not influence the rate of relapse. Subsequently, eight patients were rechallenged with a BRAFi. The median progression-free survival time after BRAFi rechallenge was 222.5 (15-425) days. The three remaining patients received treatments other than BRAFi. Our findings may be valuable with respect to ongoing clinical trials of combinations of targeted therapies and immunomodulatory antibodies.

Kharroubi Lakouas D., Huglo D., Mordon S., Vermandel M.   Nuclear medicine for photodynamic therapy in cancer: Planning, monitoring and nuclear PDT.  Photodiagnosis Photodyn. Ther..  2017 ;18 :236-243

Photodynamic therapy (PDT) is a modality with promising results for the treatment of various cancers. PDT is increasingly included in the standard of care for different pathologies. This therapy relies on the effects of light delivered to photosensitized cells. At different stages of delivery, PDT requires imaging to plan, evaluate and monitor treatment. The contribution of molecular imaging in this context is important and continues to increase. In this article, we review the contribution of nuclear medicine imaging in oncology to PDT for planning and therapeutic monitoring purposes. Several solutions have been proposed to plan PDT from nuclear medicine imaging. For instance, photosensitizer biodistribution has been evaluated with a radiolabeled photosensitizer or with conventional radiopharmaceuticals on positron emission tomography. The effects of PDT delivery have also been explored with specific SPECT or PET radiopharmaceuticals to evaluate the effects on cells (apoptosis, necrosis, proliferation, metabolism) or vascular damage. Finally, the synergy between photosensitizers and radiopharmaceuticals has been studied considering the Cerenkov effect to activate photosensitized cells.