Salah-Eddin Al-Batran

Gastric adenocarcinoma and esophageal cancer are the fifth and seventh most common cancer types worldwide. At the time of initial diagnosis, up to 50% of esophagogastric cancers present with distant metastatic lesions and are candidates for chemotherapy. Curative surgery in this stage is still an experimental approach. Only a small number of these metastatic patients show an oligometastatic disease with no uniform definition of what oligometastatic means in gastric cancer. Nevertheless, the question remains unanswered as to whether these patients are still candidates for curative concepts. Some studies have attempted to answer this question but have not been adequately designed to address the role of a curative-intended multimodal therapy in this setting. The current FLOT-5 is designed to potentially provide a definitive answer to the question of whether curatively intended surgery plays a role or is a disadvantage in this setting.

Background: Currently, complete surgical resection represents the only potentially curative treatment option for Biliary Tract Cancer (BTC) including Gallbladder Cancer (GBC). Even after curative resection, 5-year OS is only 20–40%. Gallbladder carcinoma is relatively rare, but still the fifth most common neoplasm of the digestive tract and even the most frequent cancer of the biliary system. Gallbladder carcinoma is suspected preoperatively in only 30% of all pts., while the majority of cases are discovered incidentally by the pathologist after cholecystectomy for a benign indication. For improving curative rates in BTC and GBC, early systemic therapy combined with radical resection seems to be a promising approach. The earliest moment to apply chemotherapy would be in front of radical surgery. The encouraging results of neoadjuvant/perioperative concepts in other malignancies provide an additional rationale to use this treatment in the early phase of GBC management and even ICC/ECC. Especially because data regarding pure adjuvant chemotherapy in BTC’s are conflicting. Methods: This is a multicenter, randomized, controlled, open-label phase III study including pts. with incidentally discovered GBCs after simple cholecystectomy in front of radical liver resection and pts. with resectable/ borderline resectable cholangiocarcinomas (ICC/ ECC) scheduled to receive perioperative chemotherapy (Gemcitabine + Cisplatin 3 cycles pre- and post-surgery) or surgery alone followed by a therapy of investigator’s choice. Primary endpoint is OS; secondary endpoints are PFS, R0-resection rate, toxicity, perioperative morbidity, mortality and QoL. A total of N = 333 patients with GBC or BTC will be included. Recruitment has started in August 2019. Discussion: The current proposed phase III GAIN study investigates whether induction chemotherapy followed by radical resection in ICC/ECC and re-resection in IGBC (and – if possible – postoperative chemotherapy) prolongs overall survival compared to radical surgery alone for incidental gallbladder carcinoma and primary resectable or borderline resectable cholangiocarcinoma. Utilizing a neoadjuvant approach including a second radical surgery will help to raise awareness for the necessity of radical surgery, especially second radical completion surgery in IGBC and improve the adherence to the guidelines. Trial registration: ClinicalTrials.gov ID: NCT03673072 from 17.09.2018. EudraCT number: 2017–004444-38 from 02.11.2017.

Historical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases. This is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled. If the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention. The article reports of a health care intervention on human participants and is registered on October 12, 2015 under ClinicalTrials.gov Identifier: NCT02578368 ; EudraCT: 2014–002665-30.

In vielen Studien wurden in den letzten Jahren die verschiedenen Therapieansätze miteinander verglichen. In Abhängigkeit von der Lokalisation können sowohl eine systemische Therapie (Chemotherapie) als auch alternativ eine Radiochemotherapie eingesetzt werden.

TPS4140 Background: Recent data indicates that surgical resection may bring a benefit for select patients with metastatic gastric / esophagogastric junction cancer. However, no data obtained in randomized trials is available up to now. The current RENAISSANCE trial investigates this long-lasting question about the role of surgical intervention in limited-metastatic gastric / esophagogastric junction cancer. Methods: This is a prospective, multicenter, randomized, investigator initiated phase III trial. In this study, previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) will receive 4 cycles of FLOT (docetaxel 50 mg/m²; oxaliplatin 85 mg/m²; leucovorin 200 mg/m²; 5-FU 2,600 mg/m²), and if Her2+ with trastuzumab. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will be randomized. The primary endpoint is overall survival; main secondary endpoints are quality of life parameters as assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 21 patients have been enrolled. EudraCT: 2014-002665-30. Clinical trial information: NCT02578368.