Residual Survival Research Articles

Central Nervous System Metastasis in Patients With Urothelial Carcinoma: Institutional Experience and a Comprehensive Review of the Literature.

Central nervous system (CNS) metastasis in patients with urothelial carcinoma (UC) is uncommon and poorly understood. We aimed to explore the clinical behavior and outcomes of this unique patient population. We performed a retrospective analysis of patients with UC and CNS metastasis, treated in our institution (2006-2018), along with an exploratory patient-point meta-analysis of a similar patient population derived from a comprehensive literature review. Data regarding diagnosis, management, and outcomes were extracted. Overall survival, time to CNS metastasis (TTCM), and residual survival (RS) from CNS involvement to death were calculated (Kaplan-Meier method). Cox regression was used for testing key clinicopathologic associations. We identified 20 "institutional" and 154 "literature" patients with adequate data granularity for analysis. Median TTCM was 17.7 (institutional cohort) and 10 (literature cohort) months. Most patients who developed CNS metastases had previous non-CNS metastasis (15/20 [75%] and 103/154 [67%], respectively). CNS lesions without previous history of metastasis were identified in 5/20 (25%) and 33/154 (21%) cases and those patients had a shorter TTCM. CNS lesions in the absence of known UC history were also documented in 18/154 (12%) literature cases. Multifocal CNS disease was associated with shorter RS in both cohorts in univariate, but not multivariate, analysis. We observed a variability in disease presentation and course, with a subset of patients showing an early predilection for CNS insult, potentially reflecting a diverse underlying biology. Genomic profiling studies, elucidating the molecular landscape, and driving future treatments should be considered in this setting.

Efficacy of S-1 in second-line chemotherapy after nab-paclitaxel plus gemcitabine for patients with advanced pancreatic cancer.

Second-line (2 L) chemotherapy is important for improved survival. However, the efficacy of S-1 after nab-paclitaxel plus gemcitabine (AG) for advanced pancreatic cancer (APC) remains unclear. We retrospectively investigated the clinical impact of S-1 after AG. From January 2015 to July 2018, 37 patients with APC underwent AG as first-line chemotherapy at our institute. Of these patients, 14 (38%) underwent S-1 as 2 L chemotherapy after AG (S-1 group), five (14%) received another agent after AG, and 18 (49%) underwent no 2 L chemotherapy (best supportive care [BSC] group). The clinical features were retrospectively compared between the S-1 and BSC groups. Prognostic factors for residual survival (RS) were analyzed using a Cox proportional hazards model. The induction rate of 2 L chemotherapy was 51%, and most patients received S-1 monotherapy (74%). The disease control rate and progression-free survival duration were 57.1% and 2.8 months, respectively. The median RS duration in the S-1 and BSC groups was 5.2 and 2.4 months, respectively; this difference was statistically significant (hazard ratio, 0.33; P = .005). The median overall survival duration in the S-1 and BSC groups was 12.3 and 5.0 months, respectively; this difference was also statistically significant (hazard ratio, 0.26; P = .001). The efficacy of S-1 in 2L chemotherapy for RS was identified in the multivariate analysis, as was age (<65 vs ≥65 y) and the presence of liver metastasis. The antitumor activity of S-1 was retained after AG, and the induction of S-1 after AG might improve the prognosis of patients with APC.

Palliative chemotherapy for gastroesophageal cancer in old and very old patients: A retrospective cohort study at the National Center for Tumor Diseases, Heidelberg.

To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases, Heidelberg. Using a prospectively generated database, we retrospectively analyzed 55 patients ≥ 70 years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg, Germany between January 2006 and December 2013. Further requirements for inclusion were (1) histologically proven diagnosis of gastroesophageal cancer; (2) advanced (metastatic or inoperable) disease; and (3) no history of radiation or radiochemotherapy. The clinical information included Eastern Cooperative Oncology Group performance status (ECOG PS), presence and site of metastases at diagnosis, date of previous surgery and perioperative chemotherapy, start and stop date of first-line treatment, toxicities and consecutive dosage reductions of first-line treatment, response to first-line therapy, date of progression, usage of second-line therapies and date and cause of death. Survival times [progression-free survival (PFS), overall survival (OS) and residual survival (RS)] were calculated. Toxicity and safety were examined. Prognostic factors including ECOG PS, age and previous perioperative treatment were analyzed. Median age of our cohort was 76 years. 86% of patients received a combination of two cytotoxic drugs. 76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen (69%). Drug modifications due to toxicity were necessary in 56% of patients, and 11% of patients stopped treatment due to toxicities. Survival times of our cohort are in good accordance with the major phase III trials that included mostly younger patients: PFS and OS were 5.8 and 9.5 mo, respectively. Survival differed significantly between patient groups with low (≤ 1) and high (≥ 2) ECOG PS (12.7 mo vs 3.8 mo, P < 0.001). Very old patients (≥ 75 years) did not show a worse outcome in terms of survival. Patients receiving second-line treatment (51%) had a significantly longer RS than patients with best supportive care (6.8 vs 1.4 mo, P = 0.001). Initial ECOG PS was a strong prognostic factor for PFS, OS and RS. Old patients with non-curable gastroesophageal cancer should be offered chemotherapy, and ECOG PS is a tool for balancing benefit and harm upfront. Second-line treatment is reasonable.

The role of S-1 in gemcitabine-refractory pancreatic cancer: A retrospective single-institution study

e15648 Background: S-1 was reported to be active against gemcitabine (Gem)-refractory pancreatic cancer (PaC) in Japan and was introduced in February 2005 in our institution. The aim of this study was to elucidate the impact of S-1 on prognosis of patients with Gem- refractory PaC. Methods: A total of 108 patients (pts) with advanced PaC who were treated with Gem and had disease progression (PD) at the University of Tokyo Hospital were analyzed. The introduction rates of second-line chemotherapy and the causes of introduction failure were assessed. Prognostic factors for residual survival (RS) for Gem-refractory PaC were analyzed by the Cox proportional hazard model. Results: Of 108 pts with Gem-refractory PaC, 47 pts (PreS-1 Group) had PD before February 2005, the time of S-1 introduction in our institution, and 61 pts (PostS-1 Group) after February 2005. There were no differences in baseline characteristics at PD for Gem between PreS-1 and PostS-1 Groups, except for metastasis to peritoneum more prevalent in PreS-1 Group (44.7% in PreS-1 Group and 23.0% in PostS-1 Group, p=0.023). The introduction rate of second-line chemotherapy increased from 12.8% in PreS-1 Group to 45.9% in PostS-1 Group. Second-line chemotherapy was administered in 34 pts, 29 by S-1, 4 by 5-FU-based chemoradiation, and 1 by 5-FU. The causes of introduction failure of second line chemotherapy were poor PS in 64.9%, patients’ refusal in 16.2%, infection in 2.7%, adverse effects of Gem in 1.4% and jaundice in 1.4%. RR, PFS, and OS for second-line S-1 were 17.2%, 2.5 Mo, and 7.8 Mo, respectively. PFS for Gem was not prognostic of PFS for S-1 (2.5 Mo both in pts with PFS &gt;6Mo and in pts with PFS &lt;6Mo for Gem). RS after PD for Gem was prolonged from 3.1 Mo in PreS-1 Group to 6.5 Mo in PostS-1 Group (p&lt;0.001). The Cox hazard model revealed PreS-1 Group (HR2.42, p=0.001) in addition to male gender (HR1.83, p=0.019), poor PS (HR3.52, p&lt;0.001), liver metastasis (HR2.36, p=0.037), elevated LDH (per 100U/L increase) (HR 1.30, p=0.046), elevated CRP (HR 1.14, p=0.023) at PD for Gem as poor prognostic factors of RS for Gem-refractory PaC. Conclusions: Introduction of S-1 might lead to improvement of prognosis in patients with Gem-refractory PaC. No significant financial relationships to disclose.