Papers by Fabienne Portales
Annals of Oncology, Sep 1, 2017
Background: Treatment options for pts with LAPC are limited. In the phase 3 MPACT trial, nab-P þ ... more Background: Treatment options for pts with LAPC are limited. In the phase 3 MPACT trial, nab-P þ G treatment (Tx) resulted in a > 3-fold reduction in primary pancreatic tumor burden vs G in pts with metastatic PC, suggesting that the regimen may be effective in LAPC. Interim efficacy and safety results from the international, multicenter, prospective phase 2 LAPACT trial are presented. Methods: During induction, treatment-naive pts with unresectable LAPC and ECOG PS 1 received 6 cycles of nab-P 125 mg/m 2 þ G 1000 mg/m 2 on D 1, 8, and 15 of each 28-day cycle. After induction, pts without PD or unacceptable AEs were eligible for the investigator's choice (IC) of continued Tx with nab-P þ G, chemoradiation (CRT), or surgery. Surgery could occur prior to completing 6 cycles if the investigator deemed a sufficient tumor response. The primary endpoint was TTF. A secondary endpoint was disease control rate (DCR ¼ CR, PR, and SD [ 16 weeks]) in pts who completed induction and had 1 postbaseline assessment. Data for pts who received their first dose of Tx by Oct 1, 2016 are reported. Results: A total of 101 pts with LAPC received nab-P þ G induction. Median age was 65 years (range, 42-85), and median time from primary diagnosis to first dose was 27 days. Pts received a median of 5 Tx cycles (range, 1-6). A total of 60 patients (59%) completed induction. Among 93 evaluable patients, the DCR was 82% (76/93; PR, n ¼ 33; SD 16 wks, n ¼ 43); 12 pts had SD < 16 wks, and 5 pts (5%) had PD. The most frequent reasons for discontinuation during induction (n ¼ 101 evaluable) were AEs (18%), PD (7%), and physician decision (5%). The 2 most common grade 3 AEs were neutropenia (37%) and anemia (9%). Grade 3 peripheral sensory neuropathy was reported in 4% of pts. After completion of induction, 42 patients received protocol-specific IC therapy: 13 continued nab-P þ G, 15 received CRT, and 14 underwent surgery (R0, n ¼ 4; R1, n ¼ 6; R2, n ¼ 1; 3 missing; resection conversion rate ¼ 33%). Conclusions: The reported DCR of 82% and PR rate of 35% for nab-P þ G are promising, and there were no new safety signals compared with previous studies. These interim results suggest that nab-P þ G is an appropriate LAPC Tx. NCT02301143.
Bulletin Du Cancer, 2020
Chimiothérapie périopératoire Cancer de l'estomac Docétaxel Résumé L'étude FLOT-4 montre qu'une c... more Chimiothérapie périopératoire Cancer de l'estomac Docétaxel Résumé L'étude FLOT-4 montre qu'une chimiothérapie péri-opératoire avec 5-fluorouracile, leucovorine, oxaliplatine et docétaxel (FLOT) augmente la survie des cancers de l'estomac, par rapport à une chimiothérapie de référence associant épirubicine, cisplatine et 5-fluorouracile (ou capécitabine) (ECF/ECX). FLOT serait-il ainsi devenu le nouveau standard de chimiothérapie péri-opératoire des cancers de l'estomac ? Sept cent seize patients ont été inclus dans cette étude randomisée. Trentesept pour cent des patients du groupe ECF/ECX et 46 % des patients du groupe FLOT ont reçu l'intégralité du traitement prévu (4 cures de FLOT ou 3 cures d'ECF/ECX avant et après chirurgie). L'objectif initial de FLOT-4 a été atteint ; FLOT réduit significativement la mortalité par comparaison avec ECF/ECX (HR : 0,77 ; IC 95 % : 0,63-0,94 ; p = 0,012). La médiane de survie est accrue de 15 mois par FLOT (50 mois vs 35 mois). FLOT se révèle également supérieur à ECF/ECX en taux de résection complète, en taux de réponse pathologique complète et en survie sans maladie. Le profil de toxicité des 2 traitements est différent ; à FLOT les diarrhées, les leuco-neutropénies (en particuliers sévères, 51 %), les infections (18 % d'infections sévères), la neuropathie périphérique, et à ECF/ECX, les vomissements sévères, les nausées, les troubles thromboemboliques et les anémies sévères. FLOT n'entraîne pas plus d'événements indésirables graves, de décès toxiques, et de morbi-mortalité postopératoire qu'ECF/ECX. FLOT est bien le nouveau standard de chimiothérapie péri-opératoire des cancers de l'estomac. Des interrogations subsistent toutefois dans la possibilité de transposer son utilisation en pratique quotidienne chez tous les patients.
Journal of Clinical Oncology, Jan 20, 2015
748 Background: Patients with advanced colorectal liver metastases (CRLM) experience poor prognos... more 748 Background: Patients with advanced colorectal liver metastases (CRLM) experience poor prognosis. The impact of two-stage resection (TSR) after downstaging by chemotherapy is still controversial. Methods: Data on 899 patients with CRLM in a single institution during a 9-year period (2004–2013) were prospectively collected. We used intent-to-treat analysis to evaluate the survival of patients who underwent TSR associated with intensified chemotherapy before and between the two surgical stages. Results: 73 patients were eligible for the first stage of TSR. In this population, 54 patients underwent an intensified chemotherapy based on FOLFIRINOX (26 patients) or a standard chemotherapy associated with cetuximab or bevacizumab (28 patients). The first surgical stage was a clearance of the left liver in 56% of cases. An average of two radio-frequency ablations and two wedge resections were necessary. The post-operative morbidity of the first stage was 18%. 78% of patients received chemotherapy between the two stages. The average interval between two stages was 228 days (36-1561). 68% of TSR patients completed the second stage. The second resection was mainly a standard right lobectomy (32%). Morbidity after the second resection was 12%. One patient died post-operatively because of post operative liver failure. Median overall survival of patients who completed TSR was 48 months. In contrast, there was no survival advantage for patients who underwent only the first stage because of progression (median overall survival: 19 months) (p = 0.0003). The median overall survival of the whole population was 43 months and the median recurrence-free survival was 15 months. Conclusions: Intensified chemotherapy in association with TSR allows excellent outcome in patients with advanced CRLM. Chemotherapy delivered between the two surgical stages is responsible for an important waiting time but could contribute to a better control of the evolution of the disease.
Description of patients' characteristics according to tertiles of ctDNA VAF frequency at base... more Description of patients' characteristics according to tertiles of ctDNA VAF frequency at baseline
HAL (Le Centre pour la Communication Scientifique Directe), Nov 1, 2018
Pleura and peritoneum, Dec 1, 2016
Background: Peritoneal carcinomatosis in colorectal cancer is an advanced stage of the disease wh... more Background: Peritoneal carcinomatosis in colorectal cancer is an advanced stage of the disease where improved survival can be attained whenever the resection associated with hyperthermic intreperitoneal chemotherapy is possible. In unresectable cases, systemic chemotherapy is administered to obtain conversion to resectability but results have not yet been clearly evaluated. Local chemotherapy in this setting has been proven useful in several similar situations. The aim of the present pilot study was to evaluate the feasibility of preoperative intraperitoneal chemotherapy with oxaliplatin in these patients. Methods: Six patients with unresectable peritoneal disease of colorectal origin were included in the study. An intraperitoneal implantable chamber catheter was inserted during the laparotomy that evaluated the extent of the peritoneal disease (peritoneal carcinomatosis index 25 to 39). Patients then underwent intraperitoneal chemotherapy with oxaliplatin 85 mg/m 2 in combination with systemic chemotherapy (FOLFIRI or simplified LV5FU) and a targeted therapy every 2 weeks. Results: Two catheter perfusion incidents were reported due to the abdominal wall thickness. Two patients completed the four intraperitoneal (IP) chemotherapy cycles without major toxicity. One patient developed grade 3 or 4 diarrhea requiring a short intensive care unit (ICU) stay, though it is not clear whether the event was induced by intravenous irinotecan, IP oxaliplatin or the combination of both. Grade 3 fatigue and abdominal pain were also recorded. For one patient with aggressive disease, best supportive care was initiated after the first course of chemotherapy. Conclusions: Our study is the first to assess intraperitoneal oxaliplatin-based chemotherapy in the preoperative setting for patients with unresectable peritoneal metastases. The tolerance was acceptable for 85 mg/m 2 IP oxaliplatin combined with systemic therapy in these patients. Our results justify carrying on with a phase I/II trial to determine the recommended dose of oxaliplatin in this clinical context and its efficacy.
Annals of Oncology, Sep 1, 2017
Journal of Clinical Oncology, May 20, 2016
Conclusion: OS for patients who underwent one or two LRLR is similar to those who did not have a ... more Conclusion: OS for patients who underwent one or two LRLR is similar to those who did not have a liver recurrence after primary LLR. OS is significantly lower in patients with liver recurrence who were not operated. LRLR for recurrent colorectal metastases has survival rates similar to primary laparoscopic liver resection.
Anticancer Research, Dec 29, 2021
Background: We hypothesized that perioperative FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) m... more Background: We hypothesized that perioperative FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) might be used as an alternative to standard FLOT (docetaxel, 5-fluorouracil, leucovorin, and oxaliplatin) in patients with locally advanced oesogastric adenocarcinomas (OGA), particularly those with frailties. Patients and Methods: We reviewed the charts of 61 consecutives patients treated with FOLFOX for resectable OGA to estimate overall survival, recurrence-free survival, and safety. Results: The median follow-up was 69.7 (range=3.6-97.9) months. Few patients experienced grade 3 adverse events during the preoperative (n=6; 10%) and postoperative (n=6; 16%) phases. One patient experienced a fatal grade 5 adverse events (cardiogenic shock). Median overall survival was 51.7 months [95% confidence interval (CI)=31.6-93.2 months] and the 5-year survival rate was 44.4% (95% CI=30.3%-57.5%). Conclusion: Regarding its comparable efficacy and its favourable toxicity profile, perioperative FOLFOX is a reasonable alternative to FLOT for frail patients with resectable OGA.
Annals of Surgical Oncology, Oct 25, 2018
Background. Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC... more Background. Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX. Patients and Methods. Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX ? CRT groups). Results. Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1-30); 50% (n = 102) of patients received
Digestive and Liver Disease, Dec 1, 2018
on behalf of the Thésaurus National de Cancérologie Digestive (TNCD) Soci ét é Nationale Franc ¸ ... more on behalf of the Thésaurus National de Cancérologie Digestive (TNCD) Soci ét é Nationale Franc ¸ aise de Gastroent érologie (SNFGE), F éd ération Francophone de Canc érologie Digestive (FFCD), Groupe Coop érateur multidisciplinaire en Oncologie (GERCOR), F éd ération Nationale des Centres de Lutte Contre le Cancer (UNICANCER), Soci ét é Franc ¸ aise de Chirurgie Digestive (SFCD), Soci ét é Franc ¸ aise d'Endoscopie Digestive (SFED), Soci ét é Franc ¸ aise de Radioth érapie Oncologique (SFRO), Association de Chirurgie H épato-Bilio-Pancr éatique et Transplantation (ACHBT), Association Franc ¸ aise de Chirurgie (AFC),
The Lancet Gastroenterology & Hepatology, Mar 1, 2020
n¼121), a tumor with the involvement of a relevant major artery. We assessed the association betw... more n¼121), a tumor with the involvement of a relevant major artery. We assessed the association between the resectability status, surgical outcomes, and pattern of the recurrence, including local, peritoneal, and distant recurrence. Results: The resection rate of BR-A (62%) was significantly lower than those of R (92%) and BR-V (86%). Pathological margin-negative resection was achieved in 98%, 100%, and 99% of R, BR-V, and BR-A patients, respectively. In the resected cases, the 5-year survival rate of BR-A (32%) was significantly lower than those of R (56%) and BR-V (46%). Although the 5-year cumulative incidence of local recurrence was comparable in R, BR-V, and BR-A groups (13%, 15%, and 9%, respectively), the 5-year cumulative incidences of peritoneal and distant recurrence of BR-A (35% and 60%) were significantly higher than those of BR-V (21% and 48%) and R (13% and 43%). Conclusions: In preoperative CRT, the local control in the resected cases was comparable among R, BR-V, and BR-A cases. However, the arterial involvement was associated with impaired outcomes, possibly due to the difference in the underlying pathophysiology between R/BR-V and BR-A: the advanced nature of BR-A as a systemic disease.
Cancers, Dec 20, 2022
While the role of radiation therapy in the management of pancreatic tumors remains controversial,... more While the role of radiation therapy in the management of pancreatic tumors remains controversial, new technological modalities allow for safer and more effective radiotherapy treatments. Stereotactic MR-guided Adaptive RadioTherapy (SMART) is an attractive treatment for pancreatic tumors, taking advantage of this challenging tumor location from the continuous image guidance and target tracking, as well as the daily adaptive process. We report in this prospective registry study the largest series of pancreatic SMART to date. Our study confirms the interest of this technique with a high therapeutic index since it is very well tolerated and gives encouraging results in our selected population. Pancreatic SMART could contribute to the improvement of the management of pancreatic adenocarcinoma, whose prognosis remains poor. Its exact place remains to be confirmed in further studies.
Frontiers in Oncology, Mar 9, 2022
SMART completion of 14.1 months, 76% (95% CI: 51%-89%), and 70% (95% CI: 45%-85%), respectively. ... more SMART completion of 14.1 months, 76% (95% CI: 51%-89%), and 70% (95% CI: 45%-85%), respectively. Nine patients underwent surgical resection (42.1% of patients with initial LAPC and 33.3% of patients with BRPC), with negative margins (R0). Resected patients had a significantly better OS as compared to unresected patients (p = 0.0219, hazard ratio (HR) = 5.78 (95% CI: 1.29-25.9)). SMART for pancreatic tumors is feasible without limiting toxicities. Daily adaptation demonstrated a benefit for tumor coverage and OAR sparing. The severity of observed acute and late toxicities was low. OS and LC rates were promising. SMART achieved a high secondary resection rate in LAPC patients. Surgery after SMART seemed to be feasible and might increase OS in these patients.
HAL (Le Centre pour la Communication Scientifique Directe), Oct 1, 2016
Journal of Clinical Oncology, May 20, 2016
2073Background: Brain metastases (BM) are quite rare and not well-documented in gastro-intestinal... more 2073Background: Brain metastases (BM) are quite rare and not well-documented in gastro-intestinal (GI) cancers. This prospective multicenter cohort study aimed to assess the overall survival (OS) in GI cancer patients with BM. Methods: From 2012 to 2014, 147 patients with synchronous or metachronous BM from histologically-proven GI primary tumors (PT) from 15 French centers were included. OS was defined as the time from BM diagnosis until death. Results: Patients were mainly women (64.6%); median age was 65.5 [28-92]. Histology was adenocarcinoma in 138 pts (95.8%). PT sites were mainly colorectal (71.9%), gastroesophageal (GE) (17.1%), biliary tract (7.6%). Initial staging was T3-T4 in 87 pts (65.5%), positive nodal status in 74 pts (55.2%). 61 pts (44.5) were M0, 75 pts (55.6%) were metastatic with 1, 2 or 3 sites in 42.2%, 36.3% and 21.5 %. Extra-cerebral metastases (ECM) were mostly lung (63.7%) and liver (59.3%). Median time between PT diagnosis and BM occurrence was 25.9 months [1.3-243.2]. 89 pts (...
Journal of Clinical Oncology, Jan 20, 2015
421 Background: FOLFIRINOX has already demonstrated its efficiency in metastatic pancreatic cance... more 421 Background: FOLFIRINOX has already demonstrated its efficiency in metastatic pancreatic cancer (PC). This combination need to be assessed in a neoadjuvant situation for locally advanced non metastatic PC. Methods: From 2009 to 2013, 31 patients with borderline or locally advanced PC received a neoadjuvant treatment with FOLFIRINOX so as to get them to a resectable situation. According to the tumoral response, chemoradiotherapy with gemcitabine was done. The primary analysis endpoint was the resecability rate. Pathologic response, chemotherapy’s toxicity and surgical morbidity were also evaluated. Results: Among the 31 PC, 17 were borderline resectable and 14 locally advanced according to NCCN classification. 16 (52%) received complete chemotherapy with a median of 4 cycles. Toxicity lead to treatment modification or interruption for 9 patients (29%). Grade 3-4 toxicity occurred in 7 patients (24%). 22 patients (71%) underwent chemoradiotherapy after FOLFIRINOX chemotherapy. 13 patients (42%) had disease progression under treatment whereas 18 patients with objective radiologic response or at least stable disease were surgically explored with a resection completed in 13 cases (42%). Surgical morbidity was controlled with grade 1-2 complications for 9 patients (69%) and no mortality. 11 patients (35%) demonstrated a significant pathologic response. Resected patients had a global survival median of 36 months. Conclusions: FOLFIRINOX in a neoadjuvant setting seems feasible with limited morbidity in locally advanced PC with encouraging resecability and pathologic response rates. Resected patients’ survival is promising but need to be confirmed in larger series.
Annals of Surgical Oncology, Jun 25, 2020
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
HAL (Le Centre pour la Communication Scientifique Directe), Nov 2, 2022
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
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Papers by Fabienne Portales