E. Baudin

Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis?

CONTEXTnPeritoneal carcinomatosis (PC) is a rare site of distant metastases in patients with adrenocortical cancer (ACC). One preliminary study suggests an increased risk of PC after laparoscopic adrenalectomy (LA) for ACC.nnnOBJECTIVEnThe objective of the study was to search for risk factors of PC including surgical approach.nnnDESIGNnThis was a retrospective cohort study conducted in an institutional practice.nnnPATIENTSnSixty-four consecutive patients with ACC seen at our institution between 2003 and 2009 were included. Mean tumor size was 132 mm. Patients had stage I disease in 2 cases, stage II disease in 32 cases, stage III disease in 7 cases, stage IV disease in 21 cases, and unknown stage disease in 2 cases. Surgery was open in 58 cases and laparoscopic in 6 cases.nnnMAIN OUTCOMEnThe main outcome was the risk factors of PC.nnnRESULTSnPC occurred in 18 (28%) patients. It was present at initial diagnosis in three cases and occurred during follow-up in 15 cases. The only risk factor of PC occurring during follow-up was the surgical approach with a 4-year rate of PC of 67% (95% confidence interval (CI), 30-90%) for LA and 27% (95% CI, 15-44%) for open adrenalectomy (P=0.016). Neither tumor size, stage, functional status, completeness of surgery, nor plasma level of opDDD was associated with the occurrence of PC.nnnCONCLUSIONnWe found an increased risk of PC after LA for ACC. Whether this is related to an inappropriate surgical approach or to insufficient experience in ACC surgery should be clarified by a prospective program.

Thermal ablation techniques: a curative treatment of bone metastases in selected patients?

IntroductionThermal ablation techniques (radiofrequency-ablation/cryotherapy) can be indicated with a curative intent. The success rate and prognostic factors for complete treatment were analysed.Material/methodsThe medical records of all patients who had undergone curatively intended thermal ablation of bone metastases between September 2001 and February 2012 were retrospectively analysed. The goal was to achieve complete treatment of all bone metastases in patients with oligometastatic disease (group 1) or only of bone metastases that could potentially lead to skeletal-related events in patients with a long life expectancy (group 2). We report the rate of complete treatment according to patient characteristics, primary tumour site, bone metastasis characteristics, radiofrequency ablation/cryotherapy and the treatment group (group 1/group 2).ResultsEighty-nine consecutive patients had undergone curatively intended thermal ablation of 122 bone metastases. The median follow-up was 22.8xa0months [IQRu2009=u200912.2-44.4]. In the intent-to-treat analysis, the 1-year complete treatment rate was 67xa0% (95%CI: 50xa0%-76xa0%). In the multivariate analysis the favourable prognostic factors for complete local treatment were oligometastatic status (pu2009=u20090.02), metachronous (pu2009=u20090.004) and small-sized (pu2009=u20090.001) bone metastases, without cortical bone erosion (pu2009=u20090.01) or neurological structures in the vicinity (pu2009=u20090.002).ConclusionThermal ablation should be included in the therapeutic arsenal for the cure of bone metastases.Key Points• Thermal ablation techniques are currently performed to palliate pain caused by bone metastases.• In selected patients, thermal ablation can also be indicated with a curative intent.• Oligometastatic and/or metachronous diseases are good prognostic factors for local success.• Small-size (<2xa0cm) bone metastases and no cortical erosion are good prognostic factors.

A Phase II Study of Irinotecan with 5-Fluorouracil and Leucovorin in Patients with Pretreated Gastroenteropancreatic Well-Differentiated Endocrine Carcinomas

Only a few drugs are active in the treatment of well-differentiated endocrine carcinomas (WDEC). We evaluated the combination of the so-called ‘de Gramont schedule’ and irinotecan in these tumors in a phase II study. Methods: 20 patients were enrolled in the study. The combination regimen included irinotecan, 180 mg/m2 on day 1, followed by 200 mg/m2 folinic acid in a 2-hour infusion, an intravenous 10-min bolus of 400 mg/m2 5-fluorouracil (5FU) and finally 600 mg/m2 5FU in a 22-hour infusion. Folinic acid and 5FU were repeated on day 2. Clinical, biological and morphological parameters were assessed by CT every 8 weeks. The site of the primary tumor was the pancreas in 10 cases, the lung in 3 cases and other sites in 7 cases. Sixteen patients had previously received chemotherapy, and 6 of them had had two lines of treatment. Six patients had previously been treated with chemoembolization. Results: The median number of cycles administered was 8. Grade 3–4 neutropenia was observed in 8 patients, and 1 patient experienced febrile neutropenia. There was no toxicity-related death. No complete symptomatic response was observed in 7 evaluable patients; 4 patients had an objective biological response. One patient achieved a morphological objective response, stabilization was observed in 15, but progression occurred in 3 patients. Median survival was 15 months. Conclusion: The above-mentioned combination of LV5FU2 + irinotecan does not yield major activity in heavily pretreated unresectable metastatic gastroenteropancreatic WDEC, and significant toxicity was observed.

Antiangiogenic Tyrosine Kinase Inhibitors: Occurrence and Risk Factors of Hemoptysis in Refractory Thyroid Cancer

BACKGROUNDnAntiangiogenic tyrosine kinase inhibitors (TKIs) are the mainstay of advanced thyroid cancer (TC) treatment. Concern is rising about TKI-related toxicity.nnnOBJECTIVEnTo determine the incidence and to investigate the risk factors of hemoptysis in TC patients during TKI treatment.nnnMETHODSnWe analyzed consecutive TC patients treated with TKI in our center between 2005 and 2013 and performed an independent review of computed tomography scan images for airway invasion assessment. Occurrence of grade 1-2 or grade 3-5 hemoptysis according to Common Terminology Criteria for Adverse Events version 4.03 and risk factors for hemoptysis were investigated.nnnRESULTSnA total of 140 patients (89 males; median age, 52 y) with medullary (56%), differentiated (33%), and poorly differentiated (11%) TC were enrolled. Thyroidectomy±neck dissection was performed in 123 patients and neck/mediastinum external-beam radiotherapy in 41 (32% with therapeutic purpose and 68% with adjuvant purpose). Patients received from 1 to 4 lines of TKI (median 1). Median follow-up was 24 months. Airway invasion was found in 65 (46%) cases. Hemoptysis occurred in 9 patients: grade 1-2 in 7 cases (5%) and grade 3-5 in 2 (1.4%) cases (fatal in 1). Hemoptysis was associated with presence of airway invasion (P = .04), poorly differentiated pathology (P = .03), history of therapeutic external-beam radiotherapy (P = .003), and thyroidectomy without neck dissection (P = .02).nnnCONCLUSIONnAirway invasion, poorly differentiated pathology, therapeutic external-beam radiotherapy, and thyroidectomy without neck dissection are associated with and increased risk of hemoptysis in TC patients during antiangiogenic TKI treatment. Further research is needed to confirm this data and to sort out interactions between these risk factors. A careful assessment of airway invasion is mandatory before TKI introduction.

The intensity of 18FDG uptake does not predict tumor growth in patients with metastatic differentiated thyroid cancer

PurposeIn patients with metastatic differentiated thyroid carcinoma (DTC), fluorodeoxyglucose (FDG) uptake as well as age, tumor size and radioactive iodine (RAI) uptake are prognostic factors for survival. High FDG uptake is a poor prognostic factor and lesions with high FDG uptake are often considered aggressive, but the predictive value of FDG uptake for morphological progression is unknown. The principal aim of this retrospective single center study was to determine whether the intensity of FDG uptake was correlated on a per lesion analysis with tumor growth rate (TGR) expressed as the percentage of increase in tumor size during 1xa0year (1-year TGR).MethodsFifty five patients with DTC were included between July 2012 and May 2014 with the following criteria: (i) at least one distant metastasis measuringu2009≥u20091xa0cm in diameter on CT scan (ii) evaluation by FDG-positron emission tomography/computed tomography (PET/CT) performed at our center (iii) at least one CT or another FDG-PET/CT performed 3 to 12xa0months after the reference FDG-PET/CT in the absence of systemic or local treatment between the two imaging procedures.ResultsOne hundred and fifty-six metastatic lesions located in lungs (63), neck lymph nodes (28), chest lymph nodes (42), bone (11), liver (2) and other sites (12) were studied. The median size was 16xa0mm, median SUVmax/lesion: 8.7; median metabolic tumor volume/lesion (Metab.TV/lesion): 3.7xa0cm3. The median 1-year TGR was 40.68xa0%. SUVmax and Metab.TV/lesion were not correlated to their 1-year TGR (pu2009=u20090.38 and pu2009=u20090.74 respectively). Among single patients with multiple lesions, the lesions with the highest SUVmax/lesion or the highest Metab.TV/lesion did not disclose the higher 1-year TGR.ConclusionThe intensity of FDG uptake on a per lesion analysis is not correlated to its 1-year TGR and cannot be used as a surrogate marker of tumour progression.

Interferon-alpha Treatment for Disease Control in Metastatic Pheochromocytoma/Paraganglioma Patients

Interferon-alpha (IFN-alpha) is recommended in neuroendocrine tumors (NET). Malignant pheochromocytoma and paragangliomas (MPPGLs) constitute a rare subgroup of NET with few treatment options. IFN-alpha efficacy in patients with MPPGLs was evaluated in a single-center retrospective study. Progression-free survival (PFS) was the primary endpoint according to RECIST 1.1 and/or PERCIST 1.0, and response rate, safety, and symptomatic efficacy were secondary endpoints. Fourteen patients received peginterferon alfa-2a (90 to 180xa0μg/week) or interferon alfa-2b (1.5 to 3 million unitsxa0×xa03/week) at our institution between December 2005 and February 2014 as the first (nxa0=xa07), second (nxa0=xa03), or subsequent line (nxa0=xa04) of treatment. Most of the patients had a slowly progressive disease before IFN-alpha initiation. Eight patients were men (57%); the median age was 44. At the beginning of treatment, 12 patients had progressive disease demonstrated by FDG-PET (nxa0=xa09), MIBG (nxa0=xa01), or CT scan (nxa0=xa02). Most of the patients treated (64%) had metastatic disease limited to or predominantly located in the bones. During IFN-alpha therapy, bone-directed loco-regional treatments were performed in 9 patients (range 1–4). Median PFS was 17.2xa0months (95% CI [12.1–58.3]). We observed 3 partial metabolic responses, 9 stable diseases, and 2 progressive diseases. No partial response according to RECIST 1.1 was observed. Symptomatic relief of pain, headaches, diarrhea, or sweating occurred in 6 out of 10 symptomatic pts. Most frequent all grade IFN-α-related toxicities were asthenia (nxa0=xa010), lymphopenia (nxa0=xa07), thrombopenia (nxa0=xa06), and anemia (nxa0=xa05). Median overall survival was 7.5xa0years (95% CI [4–NR]). This study suggests symptomatic response and tumor control effect with interferon-alpha in progressive MPPGLs.

Destruction préventive par thermoablation des métastases vertébrales de carcinomes thyroïdiens différenciés

Objectif Les metastases osseuses vertebrales (MV) de carcinome thyroidien differencie (CTD) sont souvent responsables d’evenements osseux vertebraux (EOV) (douleur, fracture, epidurite, compression medullaire/nerveuse), justifiant des traitements de destruction preventive. Le but de cette etude retrospective monocentrique est d’evaluer le benefice a long terme des destructions preventives par thermoablation (radiofrequence/cryotherapie) de MV de CTD. Methodes Les bilans d’imagerie et de scintigraphie d’evaluation post-thermoablation ont ete revus pour determiner les taux de traitement complet a 3xa0mois et le taux de progression tumorale a 12xa0mois, l’apparition de nouvelles MV et la survenue d’EOV, parmi les MV traitees et parmi les MV non traitees, apparues pendant la surveillance. Resultats Parmi les 28xa0patients, 41xa0MV ont ete traitees entre janvier 2008xa0et fevrier 2017xa0et suivies (duree moyennexa0: 2,7xa0±xa01.6 ans). Le taux de traitement complet a 3xa0mois etait de 87,8xa0%. Le taux d’EOV etait significativement plus faible en cas de traitement complet qu’en cas de traitement incompletxa0: 0xa0% vs 60xa0% ( n xa0=xa03xa0epidurites). Le taux de progression tumorale a 12xa0mois etait de 17,1xa0%. De nouvelles MV sont apparues chez 11xa0patients (=19xa0MV non traitees). Le taux d’EOV etait plus faible pour les lesions traitees que non traiteesxa0: 7,3xa0% versus 36,8xa0% (epidurite, n xa0=xa06xa0et fracture, n xa0=xa01). La survie sans EOV a 2 ans etait superieure pour les MV traitees que pour les MV non traiteesxa0: 92,9xa0±xa02,9xa0% versus 63,8xa0±xa05,9xa0%. Conclusion Une destruction preventive des MV par thermoablation permet de diminuer la survenue d’EOV chez les patients avec CTD.

Étude pronostique des phéochromocytomes et paragangliomes malins (étude MAPP-Prono) : étude rétrospective des réseaux COMETE et ENSAT

La stratification pronostique des pheochromocytomes et paragangliomes malins (PPM) n’est pas etablie. L’objectif principal de cette etude retrospective multicentrique des PPMs caracterises au moment du premier TDM ou IRM cervico-thoraco-abdomino-pelvienne dans les reseaux francais COMETE et europeen ENS@T entre 1998xa0et 2010, etait d’identifier des facteurs pronostiques de survie globale. Nous avons inclus 169xa0patients issus de 18xa0centres europeens dont les caracteristiques ont etes decrites lors de la SFE 2016. Le suivi median etait de 64xa0mois et la survie mediane de 6,7xa0ans. En analyse univariee, les parametres associes a une moins bonne survie etaient une localisation surrenalienne (nxa0=xa090)xa0: survie mediane de 5,63xa0ans (versus NR et 7,6xa0pour les paragangliomes du cou et abdominaux respectivement), un âgexa0>xa040xa0ansxa0: 5,8xa0et 5,2xa0ans pour les 40–60xa0ans etxa0>xa060xa0ans respectivement (versus 10,7xa0pourxa0 5xa0Nxa0: 5,2xa0ans (versus 13,6xa0et 10,7xa0pourxa0 xa02/10GC et ou Ki67xa0>xa03xa0%xa0: 4,7xa0ans (versus 10,7). En analyse multivariee, seules une maladie sporadique (pxa0=xa00,002) et des metanephrines elevees (pxa0=xa00,006) etaient des facteurs de mauvais pronostic. L’etude de la plus large cohorte de PPM ne confirme pas la mutation SDHB comme facteur de mauvais pronostic de survie. La reduction des metanephrines, marqueurs du volume secretant, devient un objectif therapeutique.

Early progression under mitotane and polychemotherapy does not mean failure in adrenocortical carcinoma patient

A 52-year-old female underwent surgery in March 2009 or a localized non-secretory adrenocortical carcinoma (ACC) f 17 cm. A Weiss score of 9 with a mitotic rate of more han 5/50HPF and a Ki67 of 10% were reported at pathology. aseline imaging work-up showed pulmonary micronodules, epatic and bones metastases and peritoneal carcinomatosis Fig. 1A). Mitotane therapy was started in April 2009, with arboplatin-etoposide (MPE) because of pejorative prognostic actors. Response to treatment was evaluated every 2 months ith CT based on RECIST 1.0 criteria and mitotane plasma evel was monitored monthly (Fig. 1). The therapeutic winow of mitotane plasma level was reached with a daily dose of g/day 4 months after treatment initiation. Furthermore, a peak f 20 mg/L was reached twice on month 4 (19.2 mg/L) and on onth 5 (20.6 mg/L). Along with that mitotane levels, a progresive disease was found until month 6 evaluation (Fig. 1B–D). maging work-up performed at month 8 after 6 cycles of EP nd 2 cycles of carboplatin-etoposide found a stable disease nd only mitotane was continued and decreased due to side ffects at maximum tolerated dose. Locoregional approaches o treat the symptomatic bones metastasis were performed at onth 10 (cimentoplasty, osteosynthesis and cryotherapy). A umor response (hepatic partial response and pulmonary comlete response) was observed for the first time 10 months after EP initiation, 2 months after the end of carboplatin-etoposide nd 6 months after mitotane peak was reached (Fig. 1F). Under itotane alone, tumor response lasted 21 months after treatment nitiation (Fig. 1G and H). At this time, because of progression in epatic targets concomitant with a plasma mitotane level above 4 mg/L, radiofrequency was performed, making RECIST criteia not usable anymore on the liver while bone metastases were ll treated with loco-regional approaches. Since 2010, the dis-

Interféron alpha pour le traitement des patients atteints de phéochromocytome/paragangliome métastatique

Objectif De nouvelles strategies therapeutiques sont necessaires pour les pheochromocytomes/paragangliomes metastatiques (PPGLM). Nous avons analyse l’efficacite antitumorale de l’interferon alpha (IFNa) chez les patients presentant un PPGLM. Methode Etude retrospective monocentrique de patients consecutifs. L’IFNa, combine a des traitements loco-regionaux, a ete evalue chez les PPGLM progressifs selon RECISTxa01.1xa0ou PERCIST. Le taux de reponse etait le critere de jugement principalxa0; la survie sans progression, la reponse symptomatique (amelioration syndrome tumoral et secretoire) et la tolerance etaient les criteres secondaires. Resultats Quatorze patients ont recu peg-IFN alpha 2A (90–180xa0mg/semaine, nxa0=xa011) ou IFN alpha 2B (1,5xa0a 3xa0MUxa0×xa03/semaine, nxa0=xa03) entre decembrexa02005xa0et fevrierxa02014xa0en premiere (nxa0=xa07), deuxieme (nxa0=xa03) ou autre (nxa0=xa04) ligne de traitement, le temps de traitement median etait de 14,4xa0mois. Quatre patients avaient des metastases exclusivement osseuses et 5xa0patients des metastases a predominance osseuse. Des traitements loco-regionaux ciblant l’os ont ete combine chez 9xa0patients. Les reponses selon RECISTxa01.1xa0ou PERCIST (en cas de maladie non evaluable RECIST) etaientxa0: 2xa0reponses partielles, 11xa0stabilisations (temps median 18xa0moisxa0; range [6–40]) et 1xa0progression. Les toxicites les plus frequentes etaientxa0: asthenie (Grade [G] 1–2xa0: nxa0=xa010, G3–4xa0: nxa0=xa02), lymphopenie (G1–2xa0: nxa0=xa07, G3–4xa0nxa0=xa01), thrombopenie (G1–2xa0: nxa0=xa06), anemie (G1–2xa0: nxa0=xa05). Une reponse symptomatique a ete observee chez 6xa0patients sur 10. Avec un suivi median de 69xa0mois, la SSP mediane etait de 14,4xa0mois (range 4–77). Conclusion Cette etude retrospective suggere un effet symptomatique et antitumoral de l’interferon alpha dans les PPGLs metastatiques.