Development and External Validation of a Model to Predict Overall Survival in Patients with Resected Gallbladder Cancer

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Elise A. J. de Savornin Lohman ◽  
T. J. J. de Bitter ◽  
G. Hannink ◽  
M. F. T. Wietsma ◽  
E. Vink-Börger ◽  
...  
BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Suyu Wang ◽  
Yue Yu ◽  
Wenting Xu ◽  
Xin Lv ◽  
Yufeng Zhang ◽  
...  

Abstract Background The prognostic roles of three lymph node classifications, number of positive lymph nodes (NPLN), log odds of positive lymph nodes (LODDS), and lymph node ratio (LNR) in lung adenocarcinoma are unclear. We aim to find the classification with the strongest predictive power and combine it with the American Joint Committee on Cancer (AJCC) 8th TNM stage to establish an optimal prognostic nomogram. Methods 25,005 patients with T1-4N0–2M0 lung adenocarcinoma after surgery between 2004 to 2016 from the Surveillance, Epidemiology, and End Results database were included. The study cohort was divided into training cohort (13,551 patients) and external validation cohort (11,454 patients) according to different geographic region. Univariate and multivariate Cox regression analyses were performed on the training cohort to evaluate the predictive performance of NPLN (Model 1), LODDS (Model 2), LNR (Model 3) or LODDS+LNR (Model 4) respectively for cancer-specific survival and overall survival. Likelihood-ratio χ2 test, Akaike Information Criterion, Harrell concordance index, integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to evaluate the predictive performance of the models. Nomograms were established according to the optimal models. They’re put into internal validation using bootstrapping technique and external validation using calibration curves. Nomograms were compared with AJCC 8th TNM stage using decision curve analysis. Results NPLN, LODDS and LNR were independent prognostic factors for cancer-specific survival and overall survival. LODDS+LNR (Model 4) demonstrated the highest Likelihood-ratio χ2 test, highest Harrell concordance index, and lowest Akaike Information Criterion, and IDI and NRI values suggested Model 4 had better prediction accuracy than other models. Internal and external validations showed that the nomograms combining TNM stage with LODDS+LNR were convincingly precise. Decision curve analysis suggested the nomograms performed better than AJCC 8th TNM stage in clinical practicability. Conclusions We constructed online nomograms for cancer-specific survival and overall survival of lung adenocarcinoma patients after surgery, which may facilitate doctors to provide highly individualized therapy.


2020 ◽  
Vol 37 (5) ◽  
pp. 390-400
Author(s):  
Yusuke Yamamoto ◽  
Teiichi Sugiura ◽  
Yukiyasu Okamura ◽  
Takaaki Ito ◽  
Ryo Ashida ◽  
...  

Background: Selecting patients who will benefit from resection among those with advanced gallbladder cancer (GBCa) having poor prognostic factors is difficult. Methods: One hundred twenty-one patients who underwent resection for stage II–IV GBCa and 19 unresected patients (unresectable group) were enrolled. The clinical impact of carbohydrate antigen 19-9 (CA19-9) and advanced surgical procedures for GBCa was evaluated. Results: The optimal CA19-9 cutoff value (based on the greatest difference in overall survival) was 250 U/mL. CA19-9 ≥250 U/mL was found to be an independent prognostic factor. Patients with CA19-9 <250 U/mL who developed jaundice (median survival time [MST], 49.1 months) or who required major hepatectomy (MST, 21.5 months) or pancreatoduodenectomy (PD; MST, 50.3 months) had a better prognosis than those with CA19-9 ≥250 U/mL who developed jaundice (MST, 16.1 months; p = 0.061) or who required major hepatectomy (MST, 9.2 months; p = 0.066) or PD (MST, 8.6 months; p = 0.025); their prognosis was comparable to that of the unresectable group (jaundice: p = 0.145, major hepatectomy: p = 0.292, PD: p = 0.756). Conclusions: Even if GBCa patients develop jaundice or require major hepatectomy, or combined PD, resection can be considered for those with CA19-9 <250 U/mL. However, surgical indication should be carefully determined in patients with CA19-9 ≥250 U/mL.


Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2073
Author(s):  
Ryota Higuchi ◽  
Takehisa Yazawa ◽  
Shuichirou Uemura ◽  
Yutaro Matsunaga ◽  
Takehiro Ota ◽  
...  

In advanced gallbladder cancer (GBC) radical resection, if multiple prognostic factors are present, the outcome may be poor; however, the details remain unclear. To investigate the poor prognostic factors affecting long-term surgical outcome, we examined 157 cases of resected stage 3/4 GBC without distant metastasis between 1985 and 2017. Poor prognostic factors for overall survival and treatment outcomes of a number of predictable preoperative poor prognostic factors were evaluated. The surgical mortality was 4.5%. In multivariate analysis, blood loss, poor histology, liver invasion, and ≥4 regional lymph node metastases (LNMs) were independent prognostic factors for poor surgical outcomes; invasion of the left margin or the entire area of the hepatoduodenal ligament and a Clavien–Dindo classification ≥3 were marginal factors. The analysis identified outcomes of patients with factors that could be predicted preoperatively, such as liver invasion ≥5 mm, invasion of the left margin or the entire area of the hepatoduodenal ligament, and ≥4 regional LNMs. Thus, the five-year overall survival was 54% for zero factors, 34% for one factor, and 4% for two factors (p < 0.05). A poor surgical outcome was likely when two or more factors were predicted preoperatively; therefore, new treatment strategies are required for such patients.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 391-391
Author(s):  
Timur Mitin ◽  
C. Kristian Enestvedt ◽  
Ahmedin Jemal ◽  
Helmneh M. Sineshaw

391 Background: There are no randomized data to guide clinicians treating patients with gallbladder cancer (GBC). Several retrospective studies reported the survival benefits of adjuvant radiotherapy (RT) and chemoradiation (CRT). The aims of this study were to examine whether these publications have impacted the utilization of adjuvant therapies and whether their survival benefits were evident in contemporary cohort of patients. Methods: Using the National Cancer Data Base, we identified 5,029 patients diagnosed with T1-3N0-1 GBC and treated with surgical resection from 2005 to 2013. We described trends in receipt of adjuvant treatments for three time periods (2005-2007, 2008-2010, 2011-2013) and calculated 3-year overall survival (OS) probabilities for 2,989 patients treated in 2005-2010. Results: The percentage of patients who received no adjuvant treatment was unchanged from 2005 to 2013. Adjuvant RT decreased from 4.3% to 1.7% (p < 0.01), adjuvant chemotherapy increased from 8% to 14% (p < 0.01), and adjuvant CRT remained stable at 16% (p = 0.98). Even for locally advanced disease (T3N0 and T1-3N1) or in the setting of positive resection margins, over 50% of patients in US did not receive adjuvant treatments. Adjuvant treatments were associated with improved 3-year overall survival in patients with resected GBC, as listed in Table. Adjuvant CRT was associated with improved survival in all stages, except T1N0, and in patients with negative and positive margins. Conclusions: Over the past decade there was no increase in the utilization of adjuvant therapies in the US for patients with resected GBC. Adjuvant therapy is associated with significantly improved 3-yr OS. In the absence of randomized data, this analysis should form the basis for clinical recommendations and national guidelines should be amended to support adjuvant treatment.[Table: see text]


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 450-450
Author(s):  
Nicha Wongjarupong ◽  
Mohamed Abdelrahim Muddathir Hassan ◽  
Cristobal T. Sanhueza ◽  
Mindy L. Hartgers ◽  
Fatima Hassan ◽  
...  

450 Background: The standard treatment for patients with gallbladder cancer is a combination of gemcitabine and cisplatin based on ABC-02 trial. However, there are no guidelines regarding treatment after first-line therapy. We retrospectively analyzed the efficacy and overall survival of different second-line regimens. Methods: We identified 203 patients with advanced gallbladder cancer who received palliative treatment between January 2000 and December 2015 at Mayo Clinic, Rochester. RECIST criteria was used to assess response. Results: 68 patients received second-line chemotherapy. Median age was 63 years (range: 32-86) and majority were males (60.6%). The median time from the diagnosis to the start of the second line chemotherapy was 8 (1-120) months. The most common used second-line chemotherapy were FOLFOX (14), gemcitabine alone (10), single agent fluoropyrimidine (11), gemcitabine with capecitabine (5), and capecitabine with oxaliplatin (4). There were 30 patients that received 5-fluorouracil based regimens, 20 patients received gemcitabine-based regimen, 3 patients received taxane-based regimen, and 15 patients received other types of chemotherapy. Median progression free survival and overall survival was 2.1 (1.8-2.7) and 16.7 (13.2-21.3) months respectively. There were 10 (52%), 11 (37%), 2 (67%), 5 (33%) with partial response and stable disease in 5-fluorouracil-based, gemcitabine-based, taxane-based, and others, respectively. There were no difference in PFS, with median PFS of 2.5, 2.0, 2.8 and 2.3 months, respectively (p=0.43). The overall survival were 15.7 (8.9-40.2), 15.0 (10.7-21.3), 40.3 (22.0-47.0), and 20.4 (9.2-30.7) months, respectively (p=0.83). There were 27 patients that received single agent chemotherapy and 41 patients that received combined regimen. There were 17 (42%) patients and 13 (48%) patients with partial response or stable disease in single and combined regimen. There were no differences in progression free survival and overall survival between single and multi agent chemotherapy. Conclusions: In this largest single institution study, second-line chemotherapy regimens for gallbladder cancer provided benefit in select patients and there is an urgent need to develop more active therapeutic regimens.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16716-e16716
Author(s):  
Syed Mohammad Ali Kazmi ◽  
Suleyman Yasin Goksu ◽  
Muhammet Ozer ◽  
Nina Niu Sanford ◽  
Matthew R. Porembka ◽  
...  

e16716 Background: Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy. Surgery remains the only potentially curative treatment for GBC. The role of neoadjuvant chemotherapy in patients with locally advanced GBC undergoing surgery is unknown. We studied the association of neoadjuvant chemotherapy on survival in locally advanced GBC patients who underwent resection. Methods: We identified adult patients with locally advanced (stage III-IV) GBC who underwent definitive surgery between 2004 and 2016 using the National Cancer Database. Treatment was categorized as neoadjuvant chemotherapy plus surgery (NAT), surgery plus adjuvant therapy (AT), and surgery alone (SA). Categorical variables were compared using the chi-square test with Bonferroni correction. Kaplan-Meier and Cox regression were used for survival analyses. We used 1:3 nearest neighbor propensity score matching based on NAT for each group. Results: Out of a total of 5,962 patients, 122 (2.2%) received NAT, 2934 (53.6%) AT, and 2421 (44.2%) SA. NAT was associated with private insurance and treatment at an academic/research facility (all p < .001) while SA patients were older, Hispanic, had government insurance, and higher comorbidities (all p < .001). Although all groups had similar lymph node assessment (NAT: 45%, AT: 46%, SA: 37%, p < .001), NAT was associated with lymph node negative disease (NAT 23%, AT 13.2%, SA 13.2%, p < .001). Median overall survival was higher in NAT compared to AT or SA (21 vs. 14 vs. 6 months, p < .001) which persisted after propensity score matching (21 vs. 15 vs. 9 months, p < .001) and multivariable regression analysis (Table). In node positive GBC, NAT was associated with improved median overall survival (NAT 24, AT 18, SA 8 months, p < .001). Conclusions: NAT is infrequently used in patients with locally advanced GBC. NAT is associated with improved median overall survival compared to AT and SA, and appears to be most beneficial in node positive disease. Prospective studies are needed to evaluate the role of neoadjuvant chemotherapy in locally advanced GB. [Table: see text]


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