Hélène Gauthier

Survival of breast cancer patients with meningeal carcinomatosis

BACKGROUND Breast cancer is the leading nonhematologic cause of meningeal carcinomatosis (MC). The aim of this study was to report the outcome of patients diagnosed with breast cancer MC and treated in single institution by a high-dose intrathecal methotrexate (MTX) regimen. METHODS Ninety-one patients were diagnosed with breast cancer MC from 2000 to 2007. Intrathecal treatment was MTX 15 mg/day (days 1-5), hydrocortisone acetate (day 1) and oral folinic acid (days 1-5), repeated every 2 weeks. Patients and tumor characteristics were associated with the early clinical and biological outcome and with the overall survival (OS). RESULTS The median survival was 4.5 months (range 0-53). In multivariate analysis, adverse prognostic factors at diagnosis were performance status >2 [P = 0.006, response rate (RR) = 0.33 (0.15-0.71)], more than three chemotherapy regimens before MC diagnosis [P = 0.03, RR = 0.40 (0.19-0.93)], negative hormone receptor status [P = 0.02, RR = 0.4 (0.19-0.90)] and high Cyfra 21-1 level [P = 0.048, RR = (0.09-0.99)]. Clinical progression after one cycle and biological response after two cycles were independently associated with OS [P < 0.001, RR = 0.09 (0.02-0.37) and P = 0.003, RR = 3.6 (1.5-8.5), respectively]. We propose a prognostic score in order to define three distinct groups of prognosis. CONCLUSIONS MC presents a poor prognosis, but 1-year survival rate was 25%. This score may become a useful tool for treatment decision and clinical trials.

MANAGEMENT OF CYSTIC CRANIOPHARYNGIOMAS WITH STEREOTACTIC ENDOCAVITARY IRRADIATION USING COLLOIDAL 186RE : A RETROSPECTIVE STUDY OF 48 CONSECUTIVE PATIENTS

OBJECTIVE We retrospectively reviewed the results of stereotactic endocavitary irradiation with colloidal 186Re in the treatment of cystic craniopharyngiomas. METHODS Among 54 consecutive patients included in a 186Re stereotactic endocavitary irradiation procedure, 42 patients (29 male and 13 female; average age, 38.7 years) received therapeutic injection via intracystic catheter introduced under stereotactic conditions. The mean follow-up period was 43 months (range, 8–148 months). Endocavitary irradiation was the primary treatment for 15 patients and an adjuvant treatment for 27 patients. The mean volume before irradiation was 8.07 mm3, and the mean radiation dose was 381 MBq. RESULTS Cystic mean volume after irradiation was 2.6 cm3 (P < 0.001 with initial volume). The retraction of the cyst was complete for 17 patients (44%) and partial for 17 (44%). In partial retraction, cystic volume decreased more than 50% for 12 (3%) patients and less than 25% (13%) for 5. Cystic volume remained the same or increased for 5 (13%) patients. Concerning visual functions, 12 (44.5%) patients improved and 2 worsened, despite tumor control. No endocrinological deterioration occurred. Among 17 patients with preoperative cognitive dysfunction, 10 improved and 6 had no change. One patient showed memory alteration 4 months after stereotactic endocavitary irradiation despite cyst volume reduction. No mortality occurred. CONCLUSION 186Re stereotactic endocavitary irradiation for the treatment of cystic craniopharyngiomas is a safe and effective procedure with a tumor control rate greater than 70%. This treatment can be used for first-intention treatment of pure cystic craniopharyngiomas or for second-intention treatment of cystic recurrences.

Contribution of lymphoscintigraphy to intraoperative sentinel lymph node detection in early cervical cancer: Analysis of the prospective multicenter SENTICOL cohort

PURPOSE To evaluate the contribution of preoperative lymphoscintigraphy to intraoperative lymphatic mapping (ILM) in early cervical cancer METHODS We conducted an ancillary analysis of the multicenter prospective SENTICOL study in early cervical cancer. Radiocolloid was injected intracervically on the day before (long protocol) or morning of (short protocol) surgery, lymphoscintigraphy was performed, and the results of a centralized image review were communicated to the surgeons. ILM was performed on combined radioactivity/patent blue detection. Sentinel lymph nodes (SLNs) were electively sampled before routine bilateral pelvic lymphadenectomy by laparoscopy. RESULTS Of 139 patients in the modified intention-to-diagnose analysis, 114 had centrally reviewed lymphoscintigrams, which showed 352 SLNs in 100 patients. Lymphoscintigraphy and ILM detection rates were 87.8% and 97.8%, respectively. Agreement between lymphoscintigraphy and ILM was low for the number of SLNs (κ=0.23; -0.04; 0.49) and bilateral SLNs (κ=0.36; 0.2; 0.52). No patient without SLNs by ILM had SLNs by lymphoscintigraphy. Lymphoscintigraphy identified substantial proportions of unusual drainage pathways. No patients with metastatic nodes had SLNs by lymphoscintigraphy but not by ILM in the relevant territory. In 1 of the 2 patients with false-negative SLN results, SLNs were bilateral by lymphoscintigraphy and unilateral by ILM. CONCLUSION Although the detection rate was lower by lymphoscintigraphy than by ILM, the substantial proportions of SLNs in unusual territories provided valuable guidance for the surgical exploration. Awareness of the limited agreement between lymphoscintigraphic and surgical detection might help surgeons decrease the false-negative rate.

Meningeal carcinomatosis in HER2-overexpressing breast cancers.

About 2% of metastatic breast cancer patients will develop meningeal carcinomatosis (MC), a life-threatening metastatic localization associated with a median overall survival as short as 4 months [1, 2]. As the blood–brain barrier may prevent intravenously delivered chemotherapy to diffuse within the cerebro-spinal fluid, the antitumor treatment is based on repeated intrathecal injections of methotrexate or thiotepa, in association with systemic chemotherapy, although no optimal regimen has been described [2, 3]. In HER2 positive metastatic breast cancer patients, the adjunction of trastuzumab or lapatinib to conventional chemotherapy showed improved antitumor efficacy, but no trial studied their use as treatment for MC. Between 2000 and 2008, about 100 breast cancer patients were diagnosed by lumbar punction a MC at Institut Curie, with a median overall survival of 4.7 months [4]. HER2 positivity was determined on the primary tumor by CB11 staining or by FISH in doubtful cases. Six patients were HER2 positive: their characteristics, treatments and overall survival are shown in Table 1. All patients received intrathecal methotrexate (according to the institutional protocol [1]) and systemic chemotherapy, in association with anti-HER2 therapy for five of them. Two patients (#3 and #6) had developed MC while being treated by adjuvant trastuzumab (authorized in France since 2005), and received lapatinib as second line of anti-HER2 treatment. Two patients (#2 and #4) have developed MC while being treated by trastuzumab and chemotherapy for metastatic breast cancer: one discontinued anti-HER2 treatment whereas the other continued to receive trastuzumab for MC. Patients #1 and #5 received trastuzumab for MC which was diagnosed at the metastatic relapse. None received intrathecal trastuzumab [5]. Although our series has a very small size, two remarks may be drawn. At first, the rate of HER2 positive cancers (n = 5/92) in our cohort suggests that HER2 positive breast cancer patients (about 15% of newly diagnosed cancers) are not at higher risk of MC. Secondly, those patients overall survival is exceptionally better than usual MC overall survivals (even better than predicted by the Curie score), except for the one who did not receive systemic HER2 targeted therapy. This observation may be due to spontaneously ‘‘favorable’’ evolutions, but also to the use of anti-HER2 therapies in adjunction with systemic and intrathecal cytotoxics. Finally, our short series shows no particular argument favouring either systemic trastuzumab or lapatinib in this setting.

Prognostic Value of Baseline Neutrophil-to-Lymphocyte Ratio in Metastatic Urothelial Carcinoma Patients Treated With First-line Chemotherapy: A Large Multicenter Study

Micro‐Abstract This multicenter study assessed the prognostic value of the neutrophile‐to‐lymphocyte ratio (NLR), a biomarker of systemic inflammation, for overall survival (OS) and progression‐free survival (PFS) after first‐line chemotherapy (CT) in 280 metastatic urothelial cancer patients. High pre‐CT NLR was an independent predictor of reduced of OS (hazard ratio = 1.36; P < .0001), highlighting the importance of an inflammatory cancer‐related microenvironment. Background: A high neutrophil‐to‐lymphocyte ratio (NLR) is a marker of systemic inflammation and is associated with poor survival in localized or metastatic cancer. This study assessed the prognostic value of NLR after first‐line chemotherapy (CT) in patients with metastatic urothelial carcinoma (mUC). Patients and Methods: Two hundred eighty consecutive patients treated with first‐line platinum‐based CT at 4 centers in France and Turkey between 2002 and 2014 were included. The association of NLR and Memorial Sloan Kettering Cancer Center (MSKCC) scores with overall survival (OS) and progression‐free survival (PFS) was determined by univariate Cox models. Results: Median OS was 10.6 months (follow‐up, 42.8 months). In univariate analysis, high NLR was associated with worse OS (hazard ratio [HR] for death = 1.36; 95% confidence interval [CI], 1.23‐1.51; P < .0001); the result was similar after adjustment for MSKCC prognostic group (HR = 1.28; 95% CI, 1.14‐1.43; P < .0001). Low NLR was associated with longer PFS (HR = 1.18; 95% CI, 1.05‐1.33; P < .005). When NLR was divided in terciles, OS in the lowest tercile (NLR 0.6‐2.78) was 12.4 to 16.6 (median, 13.4) months versus 5.3 to 9.9 (median, 7.3) months in the highest tercile (NLR 4.70‐48.9) (P = .001). Similar trends were observed for PFS (5.6‐8.9 [median, 7.6] months vs. 3.1‐5.7 [median, 4.8] months) in patients with NLR values in the lowest versus highest tercile, respectively (P = .021). Conclusion: High pre‐CT NLR was an independent prognostic factor for poor OS and PFS in mUC patients. The prognostic value of NLR, as either a continuous or categorical variable, compared favorably with MSKCC score but was easier to assess and monitor.

Méningites carcinomateuses des cancers du sein

PURPOSE Among all solid tumors breast cancer is the most common cause of meningeal carcinomatosis (MC). The purpose of this study was to analyze clinical and biological responses as well as overall survival in MC patients (pts) of breast primary treated with intrathecal methotrexate (MTX). METHODS AND MATERIALS Single-center retrospective series of MC pts treated between 2000 and 2007. Chemotherapy regimen was: MTX (15 mg/day; day 1-5) and depomedrol (40 mg, day 1) plus leucoverin (12 mg IV or 25 mg PO; day 1-5). Treatment cycles were repeated every 2 weeks. The survival was analyzed according to the characteristics of the tumor considering clinical and cytological response rates to treatment. RESULTS The median survival was 4.5 months (range 0-53). In multivariate analysis, poor prognostic factors at diagnosis were: Performans status greater than 2 [P = 0.006, RR = 0.33 (0.15-0.71)], more than three chemotherapy regimens before MC diagnosis [P = 0.03, RR = 0.40 (0.19-0.93)], negative hormone receptor status [P = 0.02, RR = 0.4 (0.19-0.90)] and high Cyfra-21-1 level [P = 0.048, RR = 0.09-0.99]. The clinical progression after one cycle and the biological response after two cycles were independently correlated with OS [P<0.001, RR = 0.09 (0.02–0.37) and P = 0.003, RR = 3.6 (1.5–8.5), respectively]. A prognostic score designed to define three groups of patients is proposed. CONCLUSION Although prognosis of patients with MC is poor, 1-year overall survival rate is 25%. The proposed prognostic score may be helpful in decision but warrants further assessment and validation in prospective trials.

TEP au FDG et cancers gynécologiques pelviens

Resume L’essor connu par la TEP au FDG dans le domaine de la cancerologie touche egalement la cancerologie gynecologique. La TEP ameliore la precision du bilan d’extension, aide au diagnostic de recidive, et peut ainsi modifier les propositions de prise en charge therapeutique. Les auteurs resument ici les principes de la TEP et ses particularites dans le domaine gynecologique, afin de comprendre les avantages et les limites de cet examen. Les grandes indications dans le cadre des cancers de l’ovaire, de l’uterus (endometre et col) et de la vulve sont passees en revues.

Bases de biologie moléculaire du cancer de la prostate résistant à la castration

Castration-resistant prostate cancer was subjected to a paradigm switch from hormone resistance to androgen deprivation therapy resistance during the last decade. Indeed, new therapeutics targeting the androgen receptor showed clinical efficacy in patients with progressive disease under castration. Thus, it is a proof that the AR remains a dominant driver of oncogenesis in earlier-called hormone resistant prostate cancer. This review summarizes the molecular mechanisms involved in castration-resistant prostate cancer.

Primary Adenocarcinoma of the Seminal Vesicle

Primary adenocarcinoma of the seminal vesicle is a rare condition with only about 60 cases described in the literature. The unusual characteristics of this disease makes diagnosis difficult and treatment strategies differ as there are no specific guidelines available. This report presents a case of adenocarcinoma of the seminal vesicle with lung metastases in which surgical and chemotherapeutic treatments have been carried out. The MVAC dose dense regimen following local resection seems effective in this scenario and may be used in the treatment of this disease.

La tomographie par émission de positons dans l’évaluation de la réponse aux thérapies ciblées

Le developpement des nouvelles therapies ciblees a mis en evidence la necessite d’une adaptation des criteres radiologiques traditionnellement utilises pour l’evaluation de la reponse tumorale, mais egalement la recherche de nouveaux criteres d’evaluation a la fois plus precoces et mieux adaptes. La medecine nucleaire, et plus particulierement la tomographie par emission de positons (TEP), offre des possibilites d’imagerie fonctionnelle variees pour l’evaluation precoce de la reponse tumorale aux therapies ciblees. La premiere partie de cet expose recense les donnees de la litterature sur la TEP au fluorodesoxyglucose (FDG) dans cette indication et en fonction du type de molecule utilisee. La seconde partie evoque les nouveaux traceurs emetteurs de positons actuellement en cours d’etude, et qui sont potentiellement interessants pour l’evaluation des modes d’action ou de l’efficacite de ces nouvelles molecules (imagerie « ciblee » de certaines voies metaboliques, de la proliferation cellulaire, de l’hypoxie, de l’angiogenese, des recepteurs, etc.).