INTRODUCTION: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). METHODS: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. RESULTS: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. DISCUSSION: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.
- MeSH
- delfská metoda MeSH
- konsensus MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádory jícnu * terapie patologie diagnóza MeSH
- nádory žaludku * terapie patologie diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
- systematický přehled MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.
- MeSH
- fluorouracil aplikace a dávkování terapeutické užití MeSH
- leukovorin aplikace a dávkování MeSH
- lidé MeSH
- nádory slinivky břišní * farmakoterapie patologie chirurgie MeSH
- neoadjuvantní terapie škodlivé účinky metody MeSH
- protokoly antitumorózní kombinované chemoterapie * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. METHODS: In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%). RESULTS: A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). CONCLUSION: The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials.
- MeSH
- delfská metoda MeSH
- lidé MeSH
- nádory * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: Consensus about the definition and treatment of oligometastatic oesophagogastric cancer is lacking. OBJECTIVE: To assess the definition and treatment of oligometastatic oesophagogastric cancer across multidisciplinary tumour boards (MDTs) in Europe. MATERIAL AND METHODS: European expert centers (n = 49) were requested to discuss 15 real-life cases in their MDT with at least a medical, surgical, and radiation oncologist present. The cases varied in terms of location and number of metastases, histology, timing of detection (i.e. synchronous versus metachronous), primary tumour treatment status, and response to systemic therapy. The primary outcome was the agreement in the definition of oligometastatic disease at diagnosis and after systemic therapy. The secondary outcome was the agreement in treatment strategies. Treatment strategies for oligometastatic disease were categorised into upfront local treatment (i.e. metastasectomy or stereotactic radiotherapy), systemic therapy followed by restaging to consider local treatment or systemic therapy alone. The agreement across MDTs was scored to be either absent/poor (<50%), fair (50%-75%), or consensus (≥75%). RESULTS: A total of 47 MDTs across 16 countries fully discussed the cases (96%). Oligometastatic disease was considered in patients with 1-2 metastases in either the liver, lung, retroperitoneal lymph nodes, adrenal gland, soft tissue or bone (consensus). At follow-up, oligometastatic disease was considered after a median of 18 weeks of systemic therapy when no progression or progression in size only of the oligometastatic lesion(s) was seen (consensus). If at restaging after a median of 18 weeks of systemic therapy the number of lesions progressed, this was not considered as oligometastatic disease (fair agreement). There was no consensus on treatment strategies for oligometastatic disease. CONCLUSION: A broad consensus on definitions of oligometastatic oesophagogastric cancer was found among MDTs of oesophagogastric cancer expert centres in Europe. However, high practice variability in treatment strategies exists.
- MeSH
- lidé MeSH
- lymfatické uzliny MeSH
- metastázektomie * MeSH
- metastázy nádorů MeSH
- nádory * MeSH
- radiochirurgie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
IMPORTANCE: The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear. OBJECTIVE: To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment. DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded. EXPOSURES: The association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise. RESULTS: We included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28; P = .93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75]; P = .004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10; P = .73). CONCLUSIONS AND RELEVANCE: These results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.
- MeSH
- adjuvantní chemoterapie MeSH
- fluorouracil MeSH
- irinotekan MeSH
- leukovorin MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory slinivky břišní * farmakoterapie patologie chirurgie MeSH
- neoadjuvantní terapie metody MeSH
- oxaliplatin MeSH
- protokoly antitumorózní kombinované chemoterapie * škodlivé účinky MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Current standard treatments for metastatic colorectal cancer (CRC) are based on combination regimens with one of the two chemotherapeutic drugs, irinotecan or oxaliplatin. However, drug resistance frequently limits the clinical efficacy of these therapies. In order to gain new insights into mechanisms associated with chemoresistance, and departing from three distinct CRC cell models, we generated a panel of human colorectal cancer cell lines with acquired resistance to either oxaliplatin or irinotecan. We characterized the resistant cell line variants with regards to their drug resistance profile and transcriptome, and matched our results with datasets generated from relevant clinical material to derive putative resistance biomarkers. We found that the chemoresistant cell line variants had distinctive irinotecan- or oxaliplatin-specific resistance profiles, with non-reciprocal cross-resistance. Furthermore, we could identify several new, as well as some previously described, drug resistance-associated genes for each resistant cell line variant. Each chemoresistant cell line variant acquired a unique set of changes that may represent distinct functional subtypes of chemotherapy resistance. In addition, and given the potential implications for selection of subsequent treatment, we also performed an exploratory analysis, in relevant patient cohorts, of the predictive value of each of the specific genes identified in our cellular models.
- MeSH
- biologické modely * MeSH
- chemorezistence * MeSH
- kamptothecin analogy a deriváty farmakologie MeSH
- kolorektální nádory * farmakoterapie genetika metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- organoplatinové sloučeniny farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cieľ Multicentrická štúdia fázy III NORDIC-VII skúmala efekt pridania cetuximabu k bolusovému fluorouracilu/ folínovej kyseline a oxaliplatine (Nordic FLOX), podávanému kontinuálne alebo intermitentne, u pacientov bez predchádzajúcej liečby pre metastatický kolorektálny karcinóm (mCRC). Taktiež bol skúmaný vplyv mutačného stavu KRAS na výsledok liečby. Pacienti a metódy Pacienti boli náhodné rozdelení buď na liečbu štandardným režimom Nordic FLOX (rameno A), kombináciu cetuximab a režim FLOX (rameno B), alebo cetuximab v kombinácii s intermitentne podávaným FLOX (rameno C). Primárnym cieľom bolo prežitie bez progresie (PFS). Celkové prežitie (OS), frekvencia odpovedí (RR), frekvencia R0 resekcií a bezpečnosť boli sekundárnymi cieľmi. Výsledky Z 571 randomizovaných pacientov bolo 566 vhodných na hodnotenie v analýzach liečebného zámeru (ITT). Mutačné analýzy KRAS a BRAF boli získané od 498 (88 %) a 457 (81 %) pacientov. Mutácie KRAS boli prítomné u 39 % nádorov; 12 % nádorov malo mutácie BRAF. Prítomnosť BRAF mutácií bola silným negatívnym prognostickým faktorom. V ITT populácii boli mediány PFS pre jednotlivé ramená 7,9, 8,3 a 7,3 mesiaca (bez signifikantných rozdielov). OS bolo takmer identické pre všetky tri skupiny (20,4, 19,7 a 20,3 mesiaca) a overené frekvencie odpovedí pre jednotlivé ramená boli 41 %, 49 % a 47 %. U pacientov s wild-type (divoký typ) KRAS tumormi pridanie cetuximabu neprinášalo dodatočný prospech v porovnaní s liečbou samotným FLOX režimom. U pacientov s KRAS mutáciami nebol detekovaný žiadny signifikantný rozdiel, hoci trend k lepšiemu PFS bol pozorovaný v ramene B. Všetky režimy boli dobre tolerované. Záver Cetuximab nepridal signifikantný prospech k režimu Nordic FLOX v prvej línii liečby mCRC.
- MeSH
- adjuvantní chemoterapie MeSH
- fluorouracil * aplikace a dávkování klasifikace terapeutické užití MeSH
- klinické zkoušky, fáze III jako téma MeSH
- kolorektální nádory * farmakoterapie MeSH
- leukovorin * aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- metastázy nádorů farmakoterapie MeSH
- monoklonální protilátky * aplikace a dávkování MeSH
- multicentrické studie jako téma MeSH
- mutační analýza DNA MeSH
- organokovové sloučeniny MeSH
- organoplatinové sloučeniny * aplikace a dávkování farmakologie terapeutické užití MeSH
- přežití MeSH
- protokoly antitumorózní kombinované chemoterapie MeSH
- protoonkogenní proteiny B-raf MeSH
- ras proteiny MeSH
- statistika jako téma MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- MeSH
- analýza přežití MeSH
- cetuximab * terapeutické užití MeSH
- DNA genetika MeSH
- doba přežití bez progrese choroby MeSH
- genotypizační techniky metody MeSH
- kolorektální nádory farmakoterapie genetika MeSH
- kombinovaná farmakoterapie MeSH
- léková rezistence MeSH
- lidé MeSH
- mutace * MeSH
- prognóza MeSH
- regresní analýza MeSH
- retrospektivní studie MeSH
- statistika jako téma MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
