Claude Krzisch

Introduction : Les carcinomes de primitif inconnu (CAPI) représentent 5% des tumeurs malignes. Avec une survie médiane de 6 à 15 mois, ils restent un défi diagnostique et thérapeutique. La connaissance des facteurs pronostiques semble capitale pour améliorer leur prise en charge. Matériel et Méthodes : Cinquante patients atteints de CAPI traités au CHU d Amiens entre 1998 et 2009 ont été analysé rétrospectivement. Leurs caractéristiques cliniques et biologiques, le traitement reçu, et d éventuels facteurs pronostiques ont été relevés puis étudiés par des méthodes univariées. Les survies ont été calculées selon la méthode de Kaplan-Meier et comparées en utilisant le test du log-rank. Résultats : Quarante-et-un patients (82%) présentaient un sous-type défavorable, dont 51,2% étaient des adénocarcinomes. Onze patients (26,8%) avaient un PS >= 2. Vingt patients (48,8%) avaient au moins 3 sites métastatiques : polyadénopathies (58,8%), os (53,7%), poumon (46,3%), foie (24,4%). Une chi...

Cette étude rétrospective, portant sur 92 patients traités entre 1992 et 2003 par radiochimiothérapie concomitante avec escalade de dose par radiothérapie externe ou curiethérapie. La population comportait des patients non métastatiques en majorité T 3 (57,1 %) et N 1 (70,3 %). Nous avons observé une médiane de survie de 10,1 mois, un taux de réponse objective au traitement de 27,1 %, un taux de récidive locorégionale de 23 % et une rechute ou la persistance d'une maladie locorégionale de 56 %. Un boost par curiethérapie a pu être effectué pour 25 patients pour lesquels on retrouve une médiane de survie de 18,1 mois avec une survie à trois ans de 44 %. La médiane de survie constatée pour les patients éligibles pour un protocole d'essai thérapeutique et de 15,6 mois avec une survie à trois ans de 25,1 %. La compliance au traitement a été de 72,8 % pour la radiothérapie et 79,1 % pour la chimiothérapie. La toxicité de grade 3 et 4 de la chimiothérapie a été de 14 % sur le plan...

To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m2 5-fluorouracil, 12 mg/m2 mitoxantrone, and 500 mg/m2 cyclophosphamide, with concomitant radiotherapy (50 Gy +/- 10-20-Gy boost). Patients in Arm B received 500 mg/m2 5-fluorouracil, 60 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p = 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.

The survival of patients with head and neck squamous cancer with locoregional recurrence is short if salvage surgery or radiation cannot be performed. Systemic chemotherapy based on platinum salts and cetuximab produces only partial and transient responses. Immune checkpoint inhibitors (i.e., nivolumab) lead to a low complete response rate of only about 10%, but in some cases the effects can be long-lasting. Intratumoral chemotherapy (ITC) has been proposed for patients with local recurrence of head and neck squamous cell carcinoma with an objective response rate of 27–50%. However, it often leads to peritumoral tissue necrosis, and the duration of local control is limited. Here, we present 2 patients with head and neck squamous cell cancer whose local recurrences were refractory to intravenous chemotherapy and nivolumab. ITC using nonnecrotizing molecules, associated with nivolumab, led to complete stable local and distant response. ITC seems to trigger tumor resensitization to pre...

A case series of Merkel cell carcinoma (MCC) is reported here and illustrates some of the current controversies in clinical management of this disease. From 1988-2007, 145 cases (74 men and 71 women) were analyzed. These were combined with other cases in the literature, hence the total number of patients was 433. Nodal metastases occurred clinically at presentation in 9/105 (9%) patients with primary tumor size <1 cm. The rate of nodal metastases is too high to obviate sentinel node biopsies even for these small tumors. For the 87 patients with intermediate tumor size (>1 - <2 cm), nodal metastases occurred clinically in 11 of 87 patients (13%) at presentation and 23 of 87 patients (26%) during follow-up. Distant metastases occurred in 20 of 87 patients (23%) only at follow-up. The risks of nodal and distant failures for tumors of intermediate sizes were sufficient to be classified as high-risk for clinical study purposes.

The results of the multimodality management of 145 cases of cutaneous Merkel cell carcinoma (MCC) are reported herein. Patient information was obtained from medical records of four Canadian institutions and one French institution. These data included ages, pathological stages, disease sites, histological and treatment details. Cause-specific survival (CSS), overall survival (OS) and disease-free survival (DFS) rates were analyzed by the log-rank and Kaplan-Meier methods. From 1988 to 2007, 145 cases were analyzed. There were 74 men and 71 women. Median age was 78 years (range 47-95.2). Median follow-up was 21.5 months (range 0.5-169.1). During the follow-up period, 37 local, 37 regional nodal and 15 distant recurrences were determined to be either solitary or multifocal sites of treatment failure. Relapsing patients were treated with multimodal treatments provided that their general state of health did not preclude this approach. Either initially and/or at relapse, 30 patients were treated with either multiagent (mostly etoposide with cisplatin or carboplatin) or single-agent chemotherapy, including irinotecan, taxotere and topotecan. In conclusion, recurrence should be treated with multimodalities. Our experience of long-term survivors after treatment of recurrence is encouraging.

Our study aims at evaluating the cost of pulsed dose-rate (PDR) brachytherapy with optimized dose distribution versus traditional treatments (iridium wires, cesium, non-optimized PDR). Issues surrounding reimbursement were also explored. This prospective, multicentre, non-randomised study conducted in the framework of a project entitled "Support Program for Costly Diagnostic and Therapeutic Innovations" involved 21 hospitals. Patients with cervix carcinoma received either classical brachytherapy or the innovation. The direct medical costs of staff and equipment, as well as the costs of radioactive sources, consumables and building renovation were evaluated from a hospital point of view using a microcosting approach. Subsequent costs per brachytherapy were compared between the four strategies. The economic study included 463 patients over two years. The main resources categories associated with PDR brachytherapy (whether optimized or not) were radioactive sources (1053euro)...

To investigate the impact of dose-volume histograms parameters on local control of three-dimensional (3D) image-based pulsed dose-rate brachytherapy (BT). Within a French multicentric prospective study, the data of the 110 patients treated for cervical cancer with external beam radiotherapy followed by 3D image-based and optimized pulsed dose-rate BT were analyzed. Delineation procedures were performed on magnetic resonance imaging in a minority of cases and on CT for the majority of cases, adapted from the Gynaecological Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology recommendations. Optimization procedure was left to the discretion of the treating center. At 2 years, local control rate reached 78%. Dose to Point A, total reference air kerma, and intermediate-risk clinical target volume (IR-CTV) V60 were predictive factors for local control (p = 0.001, p = 0.001, and p = 0.013, respectively). Patients with IR-CTV V60 <75% had a relative risk of local recurrence of 3.8 (95% confidence interval, 1.4-11.1). There was no correlation found between the high-risk clinical target volume dosimetric parameters and local control. This multicentric study has shown that 3D image-based BT provides a high local control rate for cervical cancer patients. The V60 for IR-CTV was identified as an important predictive factor for local control.

One hundred fifty-seven patients referred to the Department of Radiation Oncology of the Hôpital Tenon, Paris, France, between December 10, 1986 and December 31, 1989 for total-body irradiation (TBI) were treated according to the following two techniques: (1) either in one fraction (1000 cGy administered to the midplane at L4 and 800 cGy to the lungs) or (2) in six fractions (1200 cGy on 3 consecutive days to the midplane at L4 and 900 cGy to the lungs). The patients were randomized according to two instantaneous dose rates, called LOW and HIGH, in single-dose (6 versus 15 cGy/min) and hexafractionated (3 versus 6 cGy/min) TBI groups. There were 77 patients in the LOW group and 80 in the HIGH group, with 57 patients receiving single-dose TBI (28 LOW and 29 HIGH) and 100 patients receiving fractionated-dose TBI (49 LOW and 51 HIGH). In March 1991, the 4-year relapse-free and overall survival rates were 58.4% and 52.1%, respectively. The 4-year relapse-free survival and survival rates were 54.9% and 50.7% in the LOW group; 61.9% and 53.5% in the HIGH group (P = 0.69 and 0.82, respectively); 60.3% and 50.4% in the single-dose group; and 57.9% and 53.3% in the fractionated group (P = 0.65 and 0.78, respectively). There was no difference in the incidence of graft versus host disease, interstitial pneumonitis, or venoocclusive disease either between the LOW and the HIGH groups or between the single-dose and fractionated-dose TBI groups. The 4-year estimated cataract incidence was significantly higher in the single-dose HIGH instantaneous dose rate group than in the LOW instantaneous dose rate TBI group (P = 0.049). Multivariate analyses showed that instantaneous dose rate and fractionation do not influence the relapse-free and overall survival rates or the incidence of interstitial pneumonitis.