Advanced Gastroesophageal Junction Adenocarcinoma Research Articles

Safety and efficacy of intensified preoperative management of locally advanced gastrorsophageal junction cancer (INPROVE).

e16110 Background: The optimal management of locally advanced gastroesophageal junction adenocarcinoma (LAGEJad) is not fully established yet. Both neoadjuvant chemoradiotherapy (CRT) and perioperative taxane-based triplet chemotherapy (CT) are acknowledged treatment options for Siewert I and II cancers. In this retrospective study, we aimed to assess the safety and outcomes of an intensified preoperative regimen combining taxane-based triplet CT and CRT. Methods: We conducted a retrospective analysis of a cohort comprising 16 consecutive HER2 negative patients (pts) with LAGEJad treated at the Centro di Riferimento Oncologico of Aviano between 2019 and 2022. All pts received induction CT (iCT) consisting of fluoropyrimidine, oxaliplatin and docetaxel, followed by CRT (45Gy/25Fr) with simultaneous boost and concomitant CT. Surgery (Ivor-Lewis or McKeown) was performed 8 weeks post-CRT. Clinico-pathological (CP) and treatment features were analyzed using logistic regression to assess their association with response to iCT-CRT. The association of iCT-CRT with survival outcomes was investigated using the Kaplan-Meier method. Results: Key CP data are summarized in Table 1. Median age was 59 years, all pts were male. At diagnosis, 81.2% of pts exhibited cT3+ and cN+ disease. All pts received iCT and CRT. The rate of partial responses was 50% after iCT and 68.8% after CRT. Overall, 12 pts underwent surgery, all achieving R0 resections within a median timeframe of 9 [8.5;11] weeks post-CRT. Among them, 25% had a pathologic complete response, while 62.5% attained a Mandard tumor regression grade (TRG) of 1-2. No new safety signals emerged from iCT (only 2 pts had ≥G3 diarrhea) or CRT (≥G3 mucositis occurred in 6.2% and anemia in 6.2% of pts). No significant surgical delays were observed, although 5 pts experienced post-operative complications (4 grade I, 1 grade IIa). There were no statistically significant associations between CP variables and response to the iCT-CRT. Relapses were seen in 8 pts (2 locoregionally); 3-year survival was 46%. Median event-free survival was 5 [5;11] months, while median overall survival 34 [14;NR] months. Conclusions: The intensification of preoperative treatment in pts with LAGEJad is active and safe: the surgical schedule was not significantly delayed, and the safety profile remained comparable to standard regimens, with no major complications reported. Randomized clinical trials are ongoing to assess the clinical benefits of this approach. [Table: see text]

Tislelizumab plus chemotherapy is an optimal option for second-line treatment for advanced gastroesophageal junction adenocarcinoma.

The development of programmed cell death receptor-1 and its ligand (PD-L1) have offered new treatment options for several cancers, but the clinical benefit of tislelizumab in the gastroesophageal junction (GEJ) adenocarcinoma is still murky. Thus, we aim to investigate the efficacy and safety of tislelizumab combined with chemotherapy in patients with GEJ cancer. In this study, 90 GEJ patients were retrospectively enrolled including 45 patients who received chemotherapy plus tislelizumab while 45 underwent chemotherapy only. Overall response rate (ORR), overall survival (OS), and progression-free survival (PFS) were estimated and safety was assessed by treatment-related adverse events between two arms. The ORR was significantly higher in the tislelizumab group than in patients with chemotherapy alone (71.1 vs. 44.4%). The PFS [54.7% (47.2-62.2) vs. 33.3% (26.3-40.3), P = 0.047] and OS [62.1% (54.5-69.7) vs. 40.0% (32.5-47.5), P = 0.031] were also significantly improved in patients with concomitant use of tislelizumab. When stratified by PD-L1 combined positive score (CPS), patients with PD-L1 CPS ≥ 1 also with significantly higher PFS and OS when taking tislelizumab (P = 0.015 and P = 0.038). The incidence of hematologic toxicity was similar in the combination arm compared to the chemotherapy alone arm and the number of adverse events was not significantly increased by adding tislelizumab (all P > 0.05). Concomitant use of tislelizumab and chemotherapy in GEJ patients may be with optimal therapeutic effect and similar incidence of adverse events than chemotherapy alone. Further studies with larger number of patients are warranted to confirm it.

FLOT compared to FOLFOX/XELOX as a neoadjuvant chemotherapy in locally advanced gastric cancer: Experience of two clinics.

361 Background: The optimal regimen of neoadjuvant chemotherapy (NCT) in locally advanced gastric cancer (GC) remains controversial, especially whether triplet (FLOT) or duplet (FOLFOX/XELOX) regimen is superior since escalation does not always lead to significant clinical improvement. The aim of this study is to assess efficacy of triplet and duplet chemotherapy regimens as a neoadjuvant approach in locally advanced GC via retrospective data. Methods: We queried the data for 334 patients with locally advanced GC (cT2-4 or cN+) diagnosed in 2016–2023 yy administered with multi-agent NCT: FLOT or XELOX/FOLFOX. The primary endpoints were the ratio of patients with disease progression on NCT, rates of ypN0, and rates of pathological complete response (pCR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). Results: 156 patients (out of total 334 included in the study) received doublet NCT (FOLFOX/XELOX, 8/6 cycles respectively), 61.5% were males, median age was 67.4 (range 21.3-85.4) years, 88.2% had cT3-4. and 22.4% had locally advanced gastroesophageal junction (GEJ) adenocarcinoma. 177 patients were treated with triple NCT (FLOT, 8 cycles), 62.1% were males, median age was 59.9 years, 89.2% had cT3-4, and locally advanced GEJ adenocarcinoma was diagnosed in 21.0%. At a median follow up of 34.7 months (mth) using FLOT regimen as NCT was associated with better clinical outcomes. The ratio of patients who have progressed on NCT was 21.5% and 31% in triplet and doublet arms, respectively (p=0.098). Rates of ypN0 were 50.5% in FLOT arm and 43.7% in XELOX/FOLFOX arm (p=0.36). pCR was achieved in 8.2% and 6.3% in FLOT and XELOX/FOLFOX arms, respectively (p=0.59). Median PFS was 20.3 mth in FLOT arm in comparison to 15.7 mth in FOLFOX/XELOX arm (p=0.012). Median OS was not reached (NR) for triplet arm and was 25.1 mth for doublet arm (p= 0.003). Patients who conversed resectable disease had median PFS of 34.5 and 23.1 months for FLOT and FOLFOX/XELOX arms, respectively (p=0.024). Median OS in these subgroups was NR and 37.0 mth (p=0.003). Conclusions: We report that triplet regimen (FLOT) in comparison with doublet (FOLFOX/XELOX) regimen is the more favorable option as a neoadjuvant setting in locally advanced gastric cancer. FLOT NCT is associated with increased ypN0, pCR and shows statistically significant difference in PFS and OS.

Neoadjuvant Chemoradiotherapy versus Chemotherapy for Gastroesophageal Junction Adenocarcinoma; Which Is the Optimal Treatment Option?

Background: Locally advanced gastroesophageal junction adenocarcinoma (GEJ) is treated with either perioperative chemotherapy (CT) or preoperative radiochemotherapy (RCT) followed by surgery. The aim of this study was to compare pathologic response and long-term outcomes in junction adenocarcinoma treated with neoadjuvant RCT versus CT. Methods: All patients with locally advanced GEJ adenocarcinoma treated with neoadjuvant treatment (NAT) followed by surgery between 2009 and 2018 were retrospectively analyzed. Results: A total of 94 patients were included, 67 (71.2%) RCT and 27 (28.8%) CT. Complete pathologic response was more frequent in RCT patients (13.4% vs. 7.4%, p = 0.009) with a trend to better lymph node control (ypN0) (55.2% vs. 33.3%; p = 0.057). RCT offered no benefit in R0 resection (66.7% vs. 72.1% CT, p = 0.628) and was related to higher postoperative cardiovascular complications (35.8% vs. 11.1%; p = 0.017). Long-term overall and disease-free survival were similar (5-year OS 61.1% RCT vs. 75.7% CT, p = 0.259; 5-year DFS 33.5% RCT vs. 22.8% CT; p = 0.763). NAT type was neither independently associated with pathologic response nor long-term survival. Discussion: Patients with locally advanced GEJ adenocarcinoma treated with RCT had more postoperative cardiovascular complications but higher rates of complete pathologic response and a trend to superior locoregional lymph node control. This did not translate in a survival or recurrence benefit.

178. NEOADJUVANT CHEMORADIOTHERAPY VERSUS CHEMOTHERAPY FOR GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA; WHICH IS THE OPTIMAL TREATMENT OPTION?

Abstract Patients with locally advanced gastroesophageal junction (GEJ) adenocarcinoma are treated either with either perioperative chemotherapy (CT) or preoperative radiochemotherapy (RCT) followed by surgery. However, specific selection criteria of one modality over the other still lack, as comparative data for their efficacy remain scarce. The aim of this study was to compare pathologic response and long-term outcomes in GEJ adenocarcinoma patients treated with neoadjuvant RCT versus CT. All patients with locally advanced GEJ adenocarcinoma treated with neoadjuvant treatment (NAT) followed by surgery between 2009 and 2018 in our tertiary referral center were retrospectively analyzed. The x2 or Fisher test were used to compare categorical, and the Mann–Whitney-U test continuous variables. Survival and tumor recurrence were compared with the Kaplan Meier method and log-rank test. Multivariate logistic and Cox regression were performed to identify independent predictors of complete pathological response and long-term survival. Among the 94 included patients, 67 (71.2%) received RCT and 27 CT. Complete pathologic response was more frequent in RCT patients (13.4% vs 7.4%, p = 0.009), who had a trend to better lymph node control (ypN0) (55.2% vs 33.3%; p = 0.057), but similar rates of R0 resection (66.7% vs 72.1% CT, p = 0.628). RCT patients had more postoperative cardiovascular complications (35.8% vs 11.1%; p = 0.017). Long-term overall and disease-free survival were similar in the two groups (5-year OS 61.1% RCT vs 75.7% CT, p = 0.259; 5-year DFS 33.5% RCT vs 22.8% CT; p = 0.763). NAT type was not independently associated with pathologic response nor long-term survival. Patients with locally advanced GEJ adenocarcinoma demonstrated higher rates of complete pathologic response after neoadjuvant RCT than CT and a trend to superior locoregional lymph node sterilization, although this did not translate in a significant survival or recurrence benefit.

Multimodal management of gastroesophageal junction adenocarcinoma: Which type of neoadjuvant treatment?

Abstract Objective The current treatment for locally advanced gastroesophageal junction (GEJ) adenocarcinoma consists of neoadjuvant treatment (NAT) followed by surgery. Preoperative chemotherapy (CT) and radio-chemotherapy (RCT) are both valid options, but comparative data for their efficacy remain scarce. This study aimed to assess the efficacy of RCT and CT to achieve a complete pathologic response (CPR) for locally advanced GEJ adenocarcinoma. Secondary endpoints were R0 resection rates, postoperative complications, long-term survival and recurrence. Methods All consecutive patients with locally advanced GEJ adenocarcinoma treated with CT or RCT and oncologic resection from 2009 to 2018 were included. A CPR was defined with the Mandard tumor regression score. Standard statistical tests were used as appropriate. Overall and disease-free survival were compared with the Kaplan Meier method and log-rank test. Multivariate analysis was performed to define independent predictors of CPR, and long-term survival. Results Among the 94 patients (84%male, median age 62 years [IQR 9.7]), 67 (71.3%) received preoperative RCT and 27 (28.7%) CT. Patient’s characteristics and pretreatment tumor stages were comparable. Surgical approach was thoracoabdominal Lewis resection in 95.5% RCT and 81.5% CT patients (P = 0.085). CPR was more frequent in the RCT than the CT group (13.4% vs 7.4%, P = 0.009), but R0 resection rates were similar (72.1% vs 66.7%, P = 0.628). There was a trend to higher ypN0 stage in the RCT group (55.2% vs 33.3%; P = 0.057). Postoperatively, RCT patients presented more cardiovascular complications (35.8% vs 11.1%; P = 0.017), although overall morbidity was similar (68.6% vs 62.9%, P = 0.988). 5-year overall survival was comparable (61.1% RCT vs 75.7% CT, P = 0.259), as was 5-year disease-free survival (33.5% RCT vs 22.8% CT, P = 0.763). Isolated loco-regional recurrence occurred in 2.9% RCT vs 3.7% CT patients (P = 0.976). NAT type was not an independent predictor for complete pathologic response nor long-term survival in the multivariate analysis. Median follow-up was 30 months [95%CI 21.3-38.8] for all patients. Conclusion Patients with locally advanced GEJ adenocarcinoma demonstrated higher rates of CPR after RCT than CT, and a trend to a better lymph node sterilization, although this did not translate in a significant survival benefit or decreased recurrence rate.

Reduction of cardiac dose using respiratory-gated MR-linac plans for gastro-esophageal junction cancer

Treatment of locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) with chemoradiation may be associated with high rates of symptomatic cardiac toxicity. Large margins are typically required to ensure coverage of GEJ tumors with free-breathing volumetric modulated arc therapy (VMAT) radiotherapy. The purpose of this study is to determine whether treatment with tighter margins enabled by maximum-inhalation breath hold (MIBH)-gated intensity modulated radiation therapy (IMRT) on an integrated MRI-linear accelerator system (MR-linac) can decrease radiation doses to the heart and cardiac substructures. Ten patients with locally advanced GEJ adenocarcinoma underwent both free breathing 4-dimensional computed tomography (4DCT) and MIBH MRI simulation scans. MR-linac IMRT plans were created with a 3 mm clinical target volume (CTV) to planning target volume (PTV) isotropic margin and 4DCT VMAT plans were created with a 11, 13, and 9 mm CTV to PTV anisotropic margins in the left-right, cranial-caudal, and anterior-posterior directions according to GEJ-specific PTV expansion recommendations by Voncken et al. Prescription dose to PTV was 50.4 Gy in 28 fractions. Dosimetry to the heart and cardiac substructures was compared with paired t test; p < 0.05 was considered significant. Mean PTV on the MR-linac IMRT plans was significantly smaller compared to the 4DCT VMAT plans (689 cm3vs 1275 cm3, p < 0.01). Mean dose to the heart and all cardiac substructures was significantly lower in the MR-linac IMRT plans compared to the 4DCT VMAT plans: heart 20.9 Gy vs 27.8 Gy, left atrium 29.6 Gy vs 39.4 Gy, right atrium 20.5 Gy vs 25.6 Gy, left ventricle 21.6 Gy vs 29.6 Gy, and right ventricle 18.7 Gy vs 25.2 Gy (all p values <0.05). MIBH-gated MR-linac IMRT treatment of locally advanced GEJ adenocarcinoma can significantly decrease doses to the heart and cardiac substructures and this may translate to reduced rates of cardiac toxicity.

Gastroesophageal Junction Adenocarcinoma: Is There an Optimal Management?

The incidence of gastroesophageal junction (GEJ) adenocarcinomas has been rising over the past few decades, creating a need for effective therapeutic strategies. Treatment of locally advanced GEJ tumors, in particular, present a unique challenge because these tumors have generally been approached as either esophageal or gastric cancers, and thus optimal preoperative management remains uncertain. Both neoadjuvant chemoradiation and perioperative chemotherapy have been widely adopted in standard practice; however, it is unclear which approach offers the optimal outcome for the fit patient capable of receiving any planned strategy. In this review, we debate the management of locally advanced GEJ adenocarcinoma, and discuss areas of ongoing investigation which may provide more effective and individualized treatment of patients with GEJ cancers.

Feasibility Analysis of Involved-Field Irradiation in Patients With Locally Advanced Adenocarcinoma of the Gastroesophageal Junction in Siewert’s Type 2 and 3 Undergoing Preoperative Concurrent Chemoradiation Therapy

To analyze the feasibility of involved-field irradiation (IFI) in patients with locally advanced adenocarcinoma of gastroesophageal junction (AEG) in Siewert’s type II and III underwent preoperative concurrent chemoradiotherapy. A total of 45 cases were involved into this study. Patients received two cycles of chemotherapy with XELOX and concurrent radiotherapy (45Gy/25f, five fractions per week). After 6 to 8 weeks, they underwent operation. Patients were filled with 800 to 1000 ml water before CT simulation, and more than 5mm of stomach wall on the CT images was delineated as GTV-primary, with the reference of upper gastrointestinal barium meal, esophagus endoscopy, and MRI simultaneously. CTV provided a proximal margin of 2.0cm and distal margin of 1.5 to 2.0cm and radial of 0.8cm around the GTV-primary. GTV-nd was drawn on each relevant slice of the planning CT, and we just regarded GTV-nd and its involved area of metastasis (IFI) as CTV-nd. PTV was defined as 0.8 to 1.0cm of external expansion. The feasibility of IFI was analyzed via the postoperative pathology response and toxicity of chemoradiotherapy. Of the 45 patients, 39 completed preoperative concurrent chemoradiotherapy (CCRT), 6 underwent one cycle of chemotherapy with irradiotherapy. The R0 resection rate was 93.3% (42/45). The rate of pathological complete response (pCR) was 22.2% (10/45). The patients with tumor regression grade 0 to grade 3 were 10 (22.2%), 17 (37.8%), 15 (33.3%), 3 (6.7%), respectively. The lymph node metastasis rate and ratio were 37.8% (17/45) and 4.3% (46/1062). After neoadjuvant chemoradiotherapy, down-staging of T and N were observed in 24 and 26 patients, respectively. The proportion of pathological of stage T3∼4 had a decline by 51.1%, N positive by 42.2%, and stage III-IV by 37.8% (c2=30.896, P=0.000, c2=16.568, P=0.000, c2=17.822, P=0.000). The incidence of esophagitis/gastritis was 44.4% (20/45), and grade 1-3 were 17.8%, 22.2%, 4.4%, respectively. The rate of grade 1-2 pneumonitis was 6.6% (3/45). One patient died of treatment toxicity. A total dose of 45Gy irradiation with concurrent 2 cycles of XELOX regiment before surgery for locally advanced AEG with Siewert’s type II and III could achieve a preferable pCR and higher R0 resection. The rate of lymph node metastasis is decreased obviously, as well as T and N stage. In addition to mild toxicity, concurrent chemotherapy with IFI is worthy to be studied further.

Efficacy and Safety Analysis of Preoperative Concurrent Chemoradiation Therapy for Patients With Locally Advanced Adenocarcinoma of Gastroesophageal Junction in Siewert’s Type II III

Efficacy and Safety Analysis of Preoperative Concurrent Chemoradiation Therapy for Patients With Locally Advanced Adenocarcinoma of Gastroesophageal Junction in Siewert’s Type II III

Real world treatment patterns of previously treated advanced gastric and gastroesophageal junction adenocarcinoma (GC) in Mexico.

143 Background: Little evidence is available on the management of patients (pts) with advanced GC after 1st-line treatment (tx). Until recently, no licensed therapies for 2nd-line tx were available. This study presents real-world data on pts characteristics, tx patterns, and resource utilization for these pts in Mexico. Methods: Data from medical charts was collected from 3 centers (tertiary-level). Eligible pts were ≥ 18 years old, diagnosed Jan 2007 - Jan 2015 with advanced or metastatic GC, had received 1st-line fluoropyrimidine+platinum, had ≥ 3 months of follow-up after 1st-line discontinuation, and had not participated in a clinical trial. Data were summarized using descriptive statistics. Results: Data from 180 charts was collected; the majority from the Mexican Institute of Social Security (IMSS) (167; 92.8%). Pts' mean age was 57.2 (±12.4) years and 56.7% were male. ECOG performance status (PS) during 1st-line tx was 78.3% PS = 1, 17.2% PS = 2, 0% PS = 0. A total of 16 unique 1st-line regimes were identified, of which EOX (32.2%), XELOX (23.3%), and ECF (14.4%) were the most frequent. The most common reasons for discontinuation were completion of planned regimen (27.2%), toxicity (27.2%) and disease progression (16.7%). A total of 151 (83.9%) pts received 2nd-line chemotherapy. Of these, 54.3% were PS = 1 and 33.1% PS = 2. A total of 19 regimes were identified; with the most frequent being capecitabine (34.4%), docetaxel (16.6%), and XELOX (13.9%). Among pts who received 2nd-line chemotherapy, 50 (33.1%) received 3rd-line chemotherapy. Resource use for patients receiving 2nd-line chemotherapy was: pain interventions (7.3%), nutritional support (1.3%), radiotherapy (13.9%), transfusions (10.6%), inpatient care (15.2%), emergency room visits (2.0%) and outpatient visits (other than scheduled follow-up) (3.3%). Conclusions: This study shows considerable variation in chemotherapy regime in both 1st- and 2nd-line therapy of pts with advanced GC. Understanding GC tx patterns in Mexico will help address unmet needs. Limitations: Pts who did not receive 2nd-line tx are likely underrepresented because these pts are typically managed at local clinics and not tertiary hospitals.

Pattern of regional recurrence after curative resection in locally advanced adenocarcinoma of gastroesophageal junction: Implication for elective lymphatic target delineation of radiotherapy.

158 Background: To investigated the regional recurrence pattern of Siewert type II/III AGE patients after curative resection and refine the clinical target volume (CTV) delineation of radiotherapy. Methods: From 2009 to 2013, 78 patients who were histopathologically diagnosed with locally advanced AGE (T3/4 or any N+, Siewert II/III) after curative resection and confirmed of regional recurrence in follow-up CT images were retrospectively reviewed. First regional recurrence was recorded and one diagnostic radiologist with specialty of gastrointestinal tract investigated. Pattern of regional failure at each node station were analyzed. Reference CT images were obtained from a healthy volunteer. We then delineated the epicenters of recurrence sites at the equivalent location, based on the same vessels of reference CT images compared with the recurrence CT images on Pinnacle planning system. The combined contour of all recurrence sites was presented on a digitally reconstructed radiograph (DRR) image. Results: Most recurrence occurred within 2 years of follow-up (Median, 10.9 m). Of all, 35 (44.9%) patients had regional failure (RF) only; 24 (38%) had RF simultaneous with distant failure; 11 (14.1%) were locoregional, and 8 (10.3%) had concurrent distant and locoreginal failure. The most common recurrent node stations were No.16 (62.8%), No. 9 (32.1%), No. 11 (24.4%), No. 8 (17.9%), No. 7 (16.7%), No. 112 (12.8%), No. 4 (12.8%) and No. 12 (10.3%), respectively. 11 patients (14.1%) had recurrence at mediastinal lymph nodes. There was no significant difference of NF between Siewert type II and III AEG except for No. 9 (42.2% vs 18.2%, P = 0.027). The frequency and location of RF was shown by CT and digitally reconstructed radiograph (DRR) images. A three-dimensional (3D) atlas based on vessel delineation and distribution of RF was established. Conclusions: The most prevalent regional recurrence in Siewert type II/III AEG patients after curative resection was along the abdominal aorta, celiac artery and splenic artery. Our findings suggest a modified elective lymphatic target volume for IMRT contours in those patients.

Real-world treatment patterns of previously treated advanced gastric and gastroesophageal junction adenocarcinoma (GC) in the United Kingdom (UK).

184 Background: With no licensed therapies for previously treated advanced GC, little is known on how patients (pts) are managed after 1st-line chemotherapy (CTx) has failed. We present real-world data on characteristics, treatments, and resource utilization (RU) for such pts in the UK. Methods: Physicians who treat pts with advanced GC completed a web-based chart review detailing clinical and RU data for 3-4 de-identified pts each. Eligible pts were ≥18 years old, diagnosed Jan 2007-Mar 2012 with advanced GC, received 1st-line fluoropyrimidine+platinum, and had ≥3 months of follow-up after 1st-line discontinuation (DC). Data were summarized descriptively. Results: From Jun to Jul 2013, 58 physicians provided data for 200 pts. Pts’ mean age was 61 years; 69.5% were male. At advanced stage diagnosis, ECOG performance status (PS) was 21% 0, 72.5% 1, and 6.5% 2. The most common 1st-line regimens were capecitabine (cape)+oxaliplatin+epirubicin (epi) (34%), cape+cisplatin+epi (20.5%) and 5-FU+cisplatin+epi (13%). The most common reasons for 1st-line DC were completion of planned regimen (63%) and disease progression (24%). ECOG PS at 1st-line DC was 5% 0, 57.5% 1, 32% 2, 5.5% 3. 28.5% received 2nd-line, and 79% of these had PS 0/1 at start of 2nd-line. 21 unique 2nd-line regimens were reported; most common were docetaxel (28%), paclitaxel (11%), trastuzumab (9%), cape (7%) and irinotecan (7%). Among pts who received 2nd-line, 5% received 3rd-line. (See table.) The most common contributing reasons for hospitalization were palliative care and disease progression. Conclusions: In our study sample of advanced GC, the minority of pts received subsequent CTx after 1st-line CTx. There was considerable variation in 2nd-line regimens, although primarily monotherapy. Pts who received 2nd-line CTx had numerically similar or lower rates of supportive care. [Table: see text]

Phase I study of sunitinib with irinotecan/5-fluorouracil/ leucovorin (FOLFIRI) for advanced gastroesophageal cancers.

TPS201 Background: The incidence of gastroesophageal junction (GEJ) adenocarcinoma (AC) has dramatically increased in the Western world. Chemotherapy (CT) options have reached a plateau with median survival for advanced GEJ cancer rarely exceeding 12 months. VEGF and PDGF are strong angiogenic promoters in gastric cancer increasing proliferation, invasion and survival of the neoplastic cell. Disrupting this pathway may serve as a new therapeutic strategy in GEJ cancer. Sunitinib (S) is an oral receptor tyrosine kinase inhibitor of VEGFR, PDGRF, KIT, FLT-3, and RET. S is synergistic with CT, including 5FU in preclinical models (Mol Cancer Ther 2:471-478, 2003). We hypothesized that the addition of S to FOLFIRI in advanced GEJ AC would augment therapeutic efficacy. Methods: Primary aim is to determine the MTD of S in combination with FOLFIRI in advanced GEJ cancer. Secondary end-pts include response, overall and progression-free survival, and pharmacokinetics (PKs) of irinotecan (I), SN-38, and S (steady-state) to determine any interactions. Therapy-naïve advanced gastric and GEJ AC patients (pts) with adequate organ function, performance status (ECOG 0-1) are eligible. UGT1A1*28 7/7 homozygous polymorphism is an exclusion. Treatment consists of standard FOLFIRI (I 180 mg/m2, leucovorin 400 mg/m2, 5FU 400 mg/m2 followed by 46-hr infusion 5FU 2,400 mg/m2 q2w) with escalating doses of S given orally daily starting on day 2 (dose range 25 mg–67.5 mg, increments of 12.5 mg per cohort). Per prespecified design, initial intra- and inter-patient dose escalation was permitted, but then changed to a standard 3+3 design after observed toxicities. Initial experience also mandated amendments to an intermittent S dosing schedule of 14 days in a 28-day cycle, with decrease in I dose to 150 mg/m2, 5FU bolus to 320 mg/m2 and 5FU infusion to 2,000 mg/m2 q2w. Dose- limiting toxicities are assessed in the 1st 4 wks of treatment (febrile neutropenia, G4 neutropenia > 7d, G4 thrombocytopenia or anemia, ≥ G3 non- heme toxicity, dose delay > 14d). PKs for I/SN-38 assessed without and with S; PKs for S assessed on days 14 and 15 of cycle 1. Current accrual is at 12 pts. This study is supported by an IISP research grant from Pfizer, Inc. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer

Lymph node involvement in advanced gastroesophageal junction adenocarcinoma

The prognosis of gastroesophageal junction adenocarcinoma is unquestionably related to the extent of nodal involvement; nonetheless, few studies deal with the pattern of lymph node spread and specifically analyze the prognostic value of the site of metastasis. The present study was aimed at evaluating these key aspects in advanced gastroesophageal junction adenocarcinoma. Of 219 patients consecutively operated on for gastroesophageal junction adenocarcinoma at the Department of General Surgery and Surgical Oncology, University of Siena, and at the Department of General Surgery, University of Verona, 143 pT2-4 tumors not submitted to prior chemoradiation were analyzed according to the Japanese Gastric Cancer Association pN staging system. The majority of patients were given diagnoses of nodal metastases (77.6%). The mean number (P = .076) and the percentage of patients with pN+ disease (P = .022) progressively increased from Siewert type I to type III tumors. Abdominal nodes were involved in all but 1 of the patients with pN+ disease; conversely, nodal metastases into the chest were 46.2% for type I, 29.5% for type II, and 9.3% for type III tumors. Survival analysis showed virtually no chance of recovery for patients with more than 6 metastatic nodes or lymph nodes located beyond the first tier. In advanced gastroesophageal junction adenocarcinoma, the high frequency of nodal metastases and the related unfavorable long-term outcome achieved by means of surgical intervention alone are indicative of the need for aggressive multimodal treatment along with surgical intervention to improve long-term results.