320: Clinical Relevance of Lymph Node Status and Adjuvant Chemotherapy in Locally Advanced Bladder Cancer

575 Background: Response to neoadjuvant therapy in the primary tumor and nodal metastasis predicts benefit to patients as shown in several large clinical trials. We have previously shown that changes in tumor blood flow (BF) measured by [15O]-water PET predict pathologic primary tumor response. We now test whether primary tumor blood flow changes also predict axillary nodal metastases response and post-therapy lymph node status among women with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy. Methds: Fifty-five women with a primary diagnosis of LABC underwent dynamic [15O]-water PET scans prior to and at midpoint of neoadjuvant chemotherapy. We evaluated associations between tumor BF changes and pathologic primary tumor response: categorized as complete (CR), partial (PR) or no response (NR). We also assessed the relationship between primary tumor BF changes and post-therapy axillary lymph node status, categorizing the high risk (HR) group as 4+ nodes with extracapsular extension (ECE, n=12) versus the lower risk (LR) group with either fewer than 4+ nodes or without ECE (n=43). Results: The median changes in BF versus tumor response were: CR = -77%, PR = -40%, and, NR = +20% (P = <0.001). For axillary node response, the median BF change among HR patients was +20% versus - 49% among LR patients (P = 0.004). Eight of 17 patients with an increase in tumor blood flow were HR whereas 4/38 patients with decreased tumor blood flow were HR (P = 0.002). Conclusions: Change in primary tumor blood flow over the course of neoadjuvant chemotherapy predicts pathologic response to treatment with a substantial decrease observed among CRs. An increase in primary tumor BF with treatment portends significant residual primary tumor and a nearly 50% chance of very high-risk nodal disease post-therapy. No significant financial relationships to disclose.

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Vascular emboli as a prognostic factor in patients with stage III colorectal cancer undergoing radical surgery.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.570 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 570-570

Author(s):

Haiping Pei ◽

Qian Pei ◽

Hong Zhu ◽

Fengbo Tan

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Lymph Node ◽

Adjuvant Chemotherapy ◽

Radical Surgery ◽

Disease Free Survival ◽

Stage Iii ◽

Lymph Node Status ◽

Node Status ◽

Therapy Strategy

570 Background: The significance of vascular emboli (VE) in stage III colorectal cancer (CRC), the mechanism of their formation and their therapy strategy remain obscure demanding enhanced research. Methods: Data from 323 consecutive patients (192 non-VE, 131 VE) receiving radical surgery and adjuvant chemotherapy in our institution between Jan. 2009 and Nov. 2014 were retrospectively collected. The follow-up deadline was Feb. 2016. Potential prognostic risk factors were tested using univariate and multivariate survival analyses. mRNAs differentially expressed between VE and non-VE stage III CRC were analyzed using Agilent Gene Expression oligo-microarrays (Version 6.5). Patient-derived xenograft (PDX) nude mouse models were constructed to evaluate the efficacy of adjuvant chemotherapy plus targeted drugs (cetuximab or bevacizumab) on VE and non-VE stage III CRC. Results: VE was significantly associated with gross tumor morphology (p = 0.001), histologic type (p < 0.001), lymph node status (p < 0.001), sub-class of stage III (p =0.001), and serum CA199 level (p = 0.022). VE and lymph node status were independent risk factors for overall survival (OS) (p < 0.001, p = 0.008) and disease-free survival (DFS) (p < 0.001, p = 0.007). The median OS and DFS in VE stage III CRC patients were 38 months and 24 months, respectively. Compared with pericarcinous tissue, 809 genes (396 up-, 413 down-regulated) were differently expressed in no-VE tissue, and 1513 genes (898 up-, 615 down-regulated) in VE tissue. The top ten up-regulated protein-coding genes in VE stage III CRC were ITGBL1 (p<0.001), PROCR (p<0.001), CENPW (p<0.001), ZNF485 (p<0.001), VEGFA (p<0.001), DSG3 (p<0.001), CYP24A1 (p=0.001), COL10A1 (p=0.001), HIST3H2A (p=0.001)and PSAT1 (p=0.002). Conclusions: VE appears to be an independent risk factor for the prognosis of stage III CRC patients treated with radical surgery and adjuvant chemotherapy. Differently regulated genes seem to be involved in the formation and progress of VE. The therapy scheme should be more individualized taking into account the VE status.

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Randomized trial of adjuvant chemotherapy versus adjuvant radiation therapy for locally advanced bladder cancer after radical cystectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.4507 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 4507-4507 ◽

Cited By ~ 1

Author(s):

Mohamed S. Zaghloul ◽

John Paul Christodouleas ◽

Tarek Zaghloul ◽

Andrew Smith ◽

Ahmed Abdalla ◽

...

Keyword(s):

Clinical Trial ◽

Bladder Cancer ◽

Adjuvant Chemotherapy ◽

Radical Cystectomy ◽

Locally Advanced ◽

Disease Free Survival ◽

Phase Iii ◽

Adjuvant Radiation ◽

Advanced Bladder Cancer ◽

Grade 3

4507 Background: Some chemotherapy-naïve patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) are sufficiently de-conditioned that they are not candidates for adjuvant chemotherapy or decline it, even though such treatment may be warranted. There is no clear alternative adjuvant therapy for these patients, who are usually observed. In this study, we compare post-op radiotherapy (PORT) vs. adjuvant chemotherapy in a randomized clinical trial. We hypothesized that PORT can achieve comparable disease-free survival (DFS). Methods: A randomized phase III trial was opened to compare PORT vs. sequential chemo+PORT after RC for LABC & accrued from 2002–2008 at the NCI in Cairo. In 2007, a third arm comparing adjuvant chemo was added. Herein, we report the results of PORT vs. adjuvant chemo. Patients ≤70 y/o with ≥1 of the following factors (≥pT3b/T4a, grade 3, or positive nodes) with negative margins after RC + pelvic node dissection were eligible. Routine follow-up & pelvic CT q6 months were performed. PORT included 3D conformal pelvic RT (45Gy/1.5Gy BID). Chemo included gemcitabine/cisplatin x 4. Post-hoc non-inferiority exploratory analysis was performed. Results: The PORT arm accrued 78; the chemo arm accrued 45. 51% had urothelial carcinoma; 49% had squamous cell carcinoma/other. The two arms were well-balanced except for gender (p = 0.06). Two-year outcomes & overall adjusted hazard ratios (HR) for PORT vs. chemo alone were 54% vs. 47% (HR 0.65(95%CI 0.35-1.19, p = 0.16) for DFS; 92% vs. 69% (HR 0.28(95%CI 0.10-0.82), p = 0.02 for LRFS; 75% vs. 79% (HR 2.39(95%CI 0.94-6.09), p = 0.07) for DMFS; 61% vs. 60% (HR 0.94(95%CI 0.52-1.69), p = 0.83) for OS. Late grade ≥3 GI toxicity was observed in 6 PORT patients (8%) & 1 chemo patient (2%). Based on our data, there is a greater than 90% probability that the true difference in 2 yr DFS is less than 10%, the pre-specified non-inferiority margin. Conclusions: This randomized study demonstrates superior local control with PORT vs. adjuvant chemo with no significant differences in DFS, DMFS or OS. Results suggest that PORT could be an option for patients with LABC after RC who are medically unfit for adjuvant chemo or who decline it. Clinical trial information: NCT01734798.

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