Prognostic impact of primary tumor location in advanced urothelial carcinoma: The EORTC series.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16034-e16034
Author(s):  
Marco Moschini ◽  
Shahrokh F. Shariat ◽  
Maria De Santis ◽  
Joaquim Bellmunt ◽  
Cora N. Sternberg ◽  
...  

e16034 Background: The prognostic relevance of the primary location of urothelial cell carcinoma (UCC) on outcomes is poorly documented. This parameter has been studied in 3 EORTC trials in advanced UCC that included patients with different initial primary tumor locations. Methods: We used the data prospectively collected in three EORTC advanced UCC studies 30924 (M-VAC versus High dose M-VAC), 30986 (MCAVI versus GC, among patients unfit for CDDP), 30987 (GC-Paclitaxel versus GC, among patients fit for CDDP). Ineligible patients and other tumor locations were excluded. Patients all had measureable distant metastases or unresectable UCC and WHO performance status 0-2. Patients were grouped by primary tumor location as bladder (BCa) versus upper urinary tract (UTUC). PFS and OS by tumor location was tested in Cox proportional hazard regression stratified by study and treatment using at 2-sided α of 0.05. Results: Of the 1,039 patients, 85.3% and 14.7% patients had BCa and UTUC, respectively. Patient and disease characteristics (Table) suggested better performance status and slightly more males among patients with GCa. With a median follow up of 4.8 years (IQR:4.0-6.7), 733 deaths were recorded and 925 had progressed or died. OS and PFS did not differ significantly by tumor location overall (P=0.317 and P=0.685 respectively, Table 1), but there is significant heterogeneity across treatments (heterogeneity P=0.0450 for OS and P=0.0121 for PFS) with a suggestion of differential results in the M-CAVI arm for unfit patients. Conclusions: Primary UTUC location is uncommon in advanced UCC and did not seem to markedly impact PFS or OS. However, the findings may vary according to treatment. [Table: see text]

2019 ◽  
Vol 15 (27) ◽  
pp. 3149-3157
Author(s):  
Juan M O´Connor ◽  
Fernando Sanchez Loria ◽  
Victoria Ardiles ◽  
Jorge Grondona ◽  
Pablo Sanchez ◽  
...  

Aim: To determine the impact of KRAS mutation status on survival in patients undergoing surgery for colorectal liver metastases (CLM). Patients & methods: Patients with resected CLM and KRAS mutations. Survival was compared between mt-KRAS and wt-KRAS. Results: Of 662 patients, 174 (26.3%) were mt-KRAS and 488 (73.7%) wt-KRAS. mt-KRAS patients had significantly lower recurrence-free survival (HR: 1.42; 95% CI: 1.10–1.84). There were no differences between the groups for sidedness. Poorer survival was associated with mt-KRAS with positive lymph nodes, >1 metastases, tumors >5 cm, synchronous tumors and R1–R2. Conclusion: KRAS mutation status can help predict recurrence-free survival. Primary tumor location was not a prognostic factor after resection. KRAS mutation status can help design a multidisciplinary approach after curative resection of CLM.


2017 ◽  
Vol 28 ◽  
pp. iii118-iii119
Author(s):  
Gonçalo Atalaia ◽  
Marta Vaz Baptista ◽  
Tiago Tomás ◽  
Susana Almeida ◽  
Inês Eiriz ◽  
...  

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 741-741 ◽  
Author(s):  
Tomoyuki Nagaoka ◽  
Takeru Wakatsuki ◽  
Eiji Shinozaki ◽  
Izuma Nakayama ◽  
Mitsukuni Suenaga ◽  
...  

741 Background: Recently it has been suggested that primary tumor location may have a clinical impact on the front line chemotherapies; namely, right-sided tumor benefit less from cytotoxic and targeted agents compared with left-sided tumor. Regorafenib and TAS 102 have recently emerged and the prognostic impacts of tumor location on these agents are unknown. Methods: Clinical information of patients who were administrated Regorafenib and/or TAS 102 was retrospectively collected. Patients’ demographics by tumor location were compared using Fisher’s exact test. Time to treatment failure (TTF), and overall survival (OS) by tumor location were calculated using Kaplan-Meyer Methods and compared using Log-rank test. In addition, subgroup analyses were performed to see the interactions between tumor location and covariates in each agent. All tests were performed at the two-sided .05 significance level. Results: The median TTF (mTTF) and OS (mOS) were 2.0 and 8.0 months in the regorafenib group (n = 98) and were 2.4 and 7.9 months in the TAS102 group (n = 95), respectively. In the regorafenib group, 71 patients had a left-sided tumor and 27 patients had a right-sided tumor. In the TAS102 group, 64 patients had a left-sided and 31 patients had a right-sided tumor. There was no significant difference between right and left sides in both groups with the exception that a greater number of older patients was seen in right-sided in the TAS102 group. No significant difference of TTF and OS by primary site were observed in regorafenib (HR 0.92, 95% CI 0.68-1.70, P = 0.71 for TTF, HR 1.09, 95% CI 0.68-1.81, P = 0.74 for OS) and in TAS 102 (HR 0.84, 95%CI 0.53-1.36, P = 0.48 for TTF, HR 1.26, 95% CI 0.72-2.33 P = 0.43 for OS). Significant interactions were shown between presence of liver metastasis and tumor location both in TTF and OS in regorafenib (p < 0.05). On the other hand, in TAS102, significant interactions were shown between period from 1st line chemotherapy and tumor location in TTF and between time to metastasis and tumor location in OS (p < 0.05). Conclusions: In contrast to front line chemotherapy, no clinical impact of tumor location was demonstrated at the salvage lines in mCRC.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 628-628 ◽  
Author(s):  
Jonna Berntsson ◽  
Anna Larsson ◽  
Bjorn Nodin ◽  
Jakob Eberhard ◽  
Karin Jirstrom

628 Background: A plethora of studies report abundant expression of programmed death-ligand 1 (PD-L1) on tumors to be associated with poor outcome in several cancer forms, whereas immune cell-specific expression of PD-L1 has been associated with improved prognosis in colorectal cancer. However, none of these studies have investigated the association with prognosis according to primary tumor location. This study aimed to investigate the clinicopathological correlates and prognostic impact of PD-L1 and its receptor PD-1 in colorectal cancer, with particular reference to the anatomical subsite of the primary tumor. Methods: Immunohistochemical expression of PD-L1 and PD-1 was analysed in tissue microarrays with tumors from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. Results: High PD-L1 expression on tumor-infiltrating immune cells correlated significantly with an improved 5-year OS in univariable and multivariable analysis, adjusted for age, sex, TNM stage, differentiation grade, and vascular invasion, in the full cohort (HR = 0.49; 95 % CI 0.35-0.68), and in primary tumors of the right (HR = 0.43; 95 % CI 0.25-0.74) and the left colon (HR = 0.28; 95 % CI 0.13-0.61), but not in rectal cancer. High tumor-specific PD-L1-expression was not significantly associated with prognosis in neither the full cohort nor according to primary tumor location. High expression of PD-1 on tumor-infiltrating immune cells was significantly associated with an improved 5-year overall survival in the entire cohort (HR = 0.42; 95 % CI 0.21-0.87), but not in subsite analysis according to primary tumor location. Conclusions: This study is, to the best of our knowledge, the first to investigate the prognostic impact of PD-L1 and PD-1 expression according to primary tumor site in colorectal cancer. Dense infiltration of PD-L1+ immune cells was found to be an independent favorable prognostic factor in primary tumors of the right and left colon, but not in the rectum.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 613-613 ◽  
Author(s):  
Yu Sunakawa ◽  
Wataru Ichikawa ◽  
Akihito Tsuji ◽  
Tadamichi Denda ◽  
Yoshihiko Segawa ◽  
...  

613 Background: Sub-analyses of US and European randomized trials have demonstrated that primary tumor location is a critical prognostic factor in mCRC treated with 1st-line chemotherapy; moreover, left-sided tumor location may be a predictor of cetuximab efficacy in KRAS exon 2 wild-type tumors (Loupakis F, et al. J Natl Cancer Inst 2015; von Einem JC, et al. J Cancer Res Clin Oncol 2014). We therefore investigated the prognostic impact of primary tumor location on outcomes of Japanese pts enrolled in JACCRO CC-05 or CC-06 trial, which evaluated efficacy of cetuximab in combination with FOLFOX or SOX, respectively, for mCRC with KRAS exon 2 wild-type tumors. Methods: This study evaluated the association of tumor location with overall survival (OS) and progression-free survival (PFS) in mCRC pts from 2 phase II trials of 1st-line therapy; JACCRO CC-05 of cetuximab plus FOLFOX (n= 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n= 67, UMIN000007022). Tumors proximal or from left flexure to rectum were defined as right-sided or left-sided, respectively. Results: In total of 124 pts of the 2 trials, 110 pts were assessable for the primary tumor location: 90 pts with left-sided tumors and 20 pts with right-sided tumors. In the population consists of 110 evaluable pts, median PFS was 9.4 months, and median OS was 33.9 months. Left-sided tumors were significantly associated with longer OS (36.2 months vs. 12.6 months, HR 0.28, 95%CI 0.15-0.53, p< 0.0001) and PFS (11.1 months vs. 5.6 months, HR 0.47, 95%CI 0.29-0.82, p= 0.0041) compared to right-sided tumors. The association was evident in the group of FOLFOX (p< 0.0001 for OS and p= 0.0002 for PFS), while there was a trend in OS of the group of SOX (p= 0.079). In the FOLFOX-group, median OS and PFS were 5.7 and 3.0 months, respectively, for right-sided tumors (n= 9) and 42.8 and 11.3 months, respectively, for left-sided tumors (n= 43). Conclusions: Our study demonstrates that primary tumor location may serve as a predictor of prognosis of mCRC pts treated with cetuximab plus oxaliplatin-based therapy, potentially confirming the prognostic impact of tumor location.


2018 ◽  
Vol 118 (8) ◽  
pp. 1301-1310 ◽  
Author(s):  
Chun‐Kai Liao ◽  
Jy‐Ming Chiang ◽  
Wen‐Sy Tsai ◽  
Jeng‐Fu You ◽  
Pao‐Shiu Hsieh ◽  
...  

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