The role of adjuvant therapy after R0 resection for patients with intrahepatic and perihilar cholangiocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 302-302
Author(s):  
Young Saing Kim ◽  
Inkeun Park ◽  
Sung Yong Oh ◽  
Se-Il Go ◽  
Jung Hun Kang ◽  
...  

302 Background: There is still debated regarding the optimal treatment strategy in cholangiocarcinoma (CC) after curative resection. The aim of this study was to analyze the role of adjuvant therapy in R0-resected intrahepatic and perihilar CC. Methods: We retrospectively reviewed the medical records of patients who underwent R0 resection for intrahepatic and perihilar CC between January 2001 and December 2013 at six cancer centers. Adjuvant therapy consisted of chemotherapy (CT), chemoradiotherapy (CRT), or radiotherapy (RT). The outcomes of our study were recurrence-free survival (RFS) and overall survival (OS). Multivariable Cox proportional hazards model was used to identify prognostic factors for survival. Results: A total of 137 patients were included in the analysis; 58.4% of patients had intrahepatic CC and 25.5% had lymph node involvement. Seventy-three patients (53.3%) received adjuvant therapy (CT/CRT/RT: 48/13/12, respectively). A greater percentage of patients receiving adjuvant therapy had stage III-IVA (P = 0.010), high histologic grade (P = 0.035), and positive lymph nodes (P = 0.088). Multivariable analysis identified positive nodes (hazard ratio (HR), 3.60; P < 0.001), poor tumor differentiation (HR, 2.35, P = 0.048), and high baseline CA 19-9 level (HR, 1.97; P = 0.013) as predictors of decreased OS. The effect of adjuvant therapy varied according to the treatment modality. Adjuvant CRT was significantly associated with longer RFS (HR, 0.44; P = 0.036) but OS benefit was non-significant HR, 0.56; P = 0.245). In node-positive patients, CRT had a trend for longer OS (HR, 0.24; P = 0.097). In contrast, CT did not improve RFS (HR, 1.13; P = 0.617) or OS (HR, 1.70; P = 0.114). RT alone was associated shorter RFS (HR 3.08; P = 0.009) and OS (HR, 6.86, P < 0.001). Conclusions: Adjuvant CT and RT were not associated with a survival advantage in R0-resected intrahepatic and perihilar CC. CRT appears to be appropriate treatment after complete resection especially in lymph node-positive patients.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 355-355
Author(s):  
Young Saing Kim ◽  
In Gyu Hwang ◽  
Song-ee Park ◽  
Eun Young Kim ◽  
Jung Hun Kang ◽  
...  

355 Background: There is still debated regarding the optimal treatment strategy in cholangiocarcinoma after curative resection. The aim of this study was to analyze the role of adjuvant therapy in R0-resected distal cholangiocarcinoma. Methods: We retrospectively reviewed the medical records of patients who underwent R0 resection for distal cholangiocarcinoma between January 2001 and December 2013 at six cancer centers in Korea. Adjuvant therapy consisted of chemotherapy (CT), chemoradiotherapy (CRT), or radiotherapy (RT). Multivariable Cox proportional hazards model was used to identify prognostic factors for overall survival (OS). Results: A total of 158 patients were included in the analysis; 47 patients (29.7%) had lymph node involvement. Fifty-six patients (35.4%) received adjuvant therapy (CT/CRT/RT: 27/20/9, respectively). Patients with advanced TNM stage (p = 0.001), T3/T4 disease (p = 0.009), positive lymph nodes (p = 0.052) and elevated CA 19-9 (p = 0.071) were more likely to receive adjuvant therapy. The effect of adjuvant therapy varied according to the treatment modality. Multivariable analysis showed a significant improvement in OS with CRT (Hazard ratio (HR) 0.25, 95% CI 0.08-0.83, p = 0.024) and CT (HR 0.21, 95% CI 0.08-0.53, p = 0.001). However, RT alone was associated with shorter OS (HR 2.38, p = 0.040), along with T3/T4 disease (HR 2.12, p = 0.012) and positive lymph nodes (HR 2.30, p = 0.008). In the subset analysis according to lymph node status, adjuvant therapy not including RT alone was associated with a significant OS advantage both in node-negative patients (median, 103.3 vs. 54.9 months, p = 0.037) and node-positive patients (not reached vs. 22.6 months, p = 0.013). Conclusions: Our results showed that patients receiving adjuvant CT or CRT had significant improvement in OS. In addition, the benefit of adjuvant therapy (except RT alone) was observed even in patients with negative lymph nodes.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jason C. Sanders ◽  
Donald A. Muller ◽  
Sunil W. Dutta ◽  
Taylor J. Corriher ◽  
Kari L. Ring ◽  
...  

ObjectivesTo investigate the safety and outcomes of elective para-aortic (PA) nodal irradiation utilizing modern treatment techniques for patients with node positive cervical cancer.MethodsPatients with pelvic lymph node positive cervical cancer who received radiation were included. All patients received radiation therapy (RT) to either a traditional pelvic field or an extended field to electively cover the PA nodes. Factors associated with survival were identified using a Cox proportional hazards model, and toxicities between groups were compared with a chi-square test.Results96 patients were identified with a mean follow up of 40 months. The incidence of acute grade ≥ 2 toxicity was 31% in the elective PA nodal RT group and 15% in the pelvic field group (Chi-square p = 0.067. There was no significant difference in rates of grade ≥ 3 acute or late toxicities between the two groups (p&gt;0.05). The KM estimated 5-year OS was not statistically different for those receiving elective PA nodal irradiation compared to a pelvic only field, 54% vs. 73% respectively (log-rank p = 0.11).ConclusionsElective PA nodal RT can safely be delivered utilizing modern planning techniques without a significant increase in severe (grade ≥ 3) acute or late toxicities, at the cost of a possible small increase in non-severe (grade 2) acute toxicities. In this series there was no survival benefit observed with the receipt of elective PA nodal RT, however, this benefit may have been obscured by the higher risk features of this population. While prospective randomized trials utilizing a risk adapted approach to elective PA nodal coverage are the only way to fully evaluate the benefit of elective PA nodal coverage, these trials are unlikely to be performed and instead we must rely on interpretation of results of risk adapted approaches like those used in ongoing clinical trials and retrospective data.


2016 ◽  
Vol 10 (9-10) ◽  
pp. 321 ◽  
Author(s):  
R. Christopher Doiron ◽  
Melanie Jaeger ◽  
Christopher M. Booth ◽  
Xuejiao Wei ◽  
D. Robert Siemens

Introduction: Thoracic epidural analgesia (TEA) is commonly used to manage postoperative pain and facilitate early mobilization after major intra-abdominal surgery. Evidence also suggests that regional anesthesia/analgesia may be associated with improved survival after cancer surgery. Here, we describe factors associated with TEA at the time of radical cystectomy (RC) for bladder cancer and its association with both short- and long-term outcomes in routine clinical practice.Methods: All patients undergoing RC in the province of Ontario between 2004 and 2008 were identified using the Ontario Cancer Registry (OCR). Modified Poisson regression was used to describe factors associated with epidural use, while a Cox proportional hazards model describes associations between survival and TEA use.Results: Over the five-year study period, 1628 patients were identified as receiving RC, 54% (n=887) of whom received TEA. Greater anesthesiologist volume (lowest volume providers relative risk [RR] 0.85, 95% confidence interval [CI] 0.75‒0.96) and male sex (female sex RR 0.89, 95% CI 0.79‒0.99) were independently associated with greater use of TEA. TEA use was not associated with improved short-term outcomes. In multivariable analysis, TEA was not associated with cancer-specific survival (hazard ratio [HR] 1.02, 95% CI 0.87‒1.19; p=0.804) or overall survival (HR 0.91, 95% CI 0.80‒1.03; p=0.136).Conclusions: In routine clinical practice, 54% of RC patients received TEA and its use was associated with anesthesiologist provider volume. After controlling for patient, disease and provider variables, we were unable to demonstrate any effect on either short- or long-term outcomes at the time of RC.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 518-518
Author(s):  
Nathan Colin Wong ◽  
Shawn Dason ◽  
Lucas W. Dean ◽  
Sumit Isharwal ◽  
Mark Donoghue ◽  
...  

518 Background: Late relapse (>2 years) GCT is associated with an increased rate of SSM. We report our experience with SSM in the setting of late relapse and determine predictors of overall survival (OS). Methods: From 1985 to 2018, 46 patients with GCT and SSM at late relapse were identified. Clinical and pathologic parameters were reviewed. The Kaplan-Meier method was used to estimate OS from time of relapse and a Cox proportional hazards model to assess predictors of OS. Results: Of 46 men (44 testicular primary, 2 mediastinal primary), median time to late relapse with SSM was 10.4 years (range, 2.3 - 38.1). Most (n=27, 59%) were symptomatic at presentation but 11 were detected by elevated tumor markers (AFP 8, HCG 2, both 1) and 8 by surveillance imaging. SSMs were adenocarcinoma (25), sarcoma (14), poorly differentiated neoplasm (3), Wilms (2), PNET (1) and glioma (1). Median time to relapse was longer for adenocarcinoma vs other histotypes of SSM (14.6 vs 4.1 years, p < 0.001). The initial site of relapse was the retroperitoneum (RP, 26), pelvis (7), lung (6), retrocrural space (3), mediastinum (2), neck (1) and duodenum (1). Only 10 of 26 men with late relapse in the RP had undergone prior RPLND (all at outside institutions; variable templates) with histology in 7/10 showing teratoma. The other 16 men had received chemotherapy only (8), orchiectomy only for stage I (3), RPLND aborted due to cardiac arrest (1), and unknown (4). All 46 late relapses were managed with surgical resection; 26 also received chemotherapy (16 SSM-directed, 10 GCT-directed). Overall, 12 patients died and the median OS was 14.2 years. On univariable analysis, symptomatic presentation (HR = 3.1), SSM at multiple sites (HR = 3.9), extra-RP disease (HR: 3.9), and incomplete/no resection of SSM (HR = 3.6) predicted mortality. On multivariable analysis, only extra-RP disease was independently associated with inferior OS (5-year OS, 82 vs 52%, p = 0.017). Conclusions: SSM is an important potential complication of late relapse GCT and seems to be associated with the lack of resection of retroperitoneal metastases. Early identification and complete surgical resection prior to SSM arising in extra-RP sites is critical to optimizing outcomes.


Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4286
Author(s):  
Pui-Lam Yip ◽  
Shing-Fung Lee ◽  
Cheuk-Wai Horace Choi ◽  
Po-Chung Sunny Chan ◽  
Ka-Wai Alice Cheung ◽  
...  

A nomogram was recently published by Sun et al. to predict overall survival (OS) and the additional benefit of concurrent chemoradiation (CCRT) vs. radiotherapy (RT) alone, in stage II NPC treated with conventional RT. We aimed to assess the predictors of OS and to externally validate the nomogram in the IMRT era. We analyzed stage II NPC patients treated with definitive RT alone or CCRT between 2001 and 2011 under the territory-wide Hong Kong NPC Study Group 1301 study. Clinical parameters were studied using the Cox proportional hazards model to estimate OS. The nomogram by Sun et al. was applied with 1000 times bootstrap resampling to calculate the concordance index, and we compared the nomogram predicted and observed 5-year OS. There were 482 patients included. The 5-year OS was 89.0%. In the multivariable analysis, an age > 45 years was the only significant predictor of OS (HR, 1.98; 95%CI, 1.15–3.44). Other clinical parameters were insignificant, including the use of CCRT (HR, 0.99; 95%CI, 0.62–1.58). The nomogram yielded a concordance index of 0.55 (95% CI, 0.49–0.62) which lacked clinically meaningful discriminative power. The nomogram proposed by Sun et al. should be interpreted with caution when applied to stage II NPC patients in the IMRT era. The benefit of CCRT remained controversial.


BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e033965
Author(s):  
Lixian Li ◽  
Zijing Yang ◽  
Yawen Hou ◽  
Zheng Chen

ObjectivesThis study explored the prognostic factors and developed a prediction model for Chinese-American (CA) cervical cancer (CC) patients. We compared two alternative models (the restricted mean survival time (RMST) model and the proportional baselines landmark supermodel (PBLS model, producing dynamic prediction)) versus the Cox proportional hazards model in the context of time-varying effects.Setting and data sourcesA total of 713 CA women with CC and available covariates (age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and radiation) from the Surveillance, Epidemiology and End Results database were included.DesignWe applied the Cox proportional hazards model to analyse the all-cause mortality with the proportional hazards assumption. Additionally, we applied two alternative models to analyse covariates with time-varying effects. The performances of the models were compared using the C-index for discrimination and the shrinkage slope for calibration.ResultsOlder patients had a worse survival rate than younger patients. Advanced FIGO stage patients showed a relatively poor survival rate and low life expectancy. Lymph node metastasis was an unfavourable prognostic factor in our models. Age at diagnosis, FIGO stage and lymph node metastasis represented time-varying effects from the PBLS model. Additionally, radiation showed no impact on survival in any model. Dynamic prediction presented a better performance for 5-year dynamic death rates than did the Cox proportional hazards model.ConclusionsWith the time-varying effects, the RMST model was suggested to explore diagnosis factors, and the PBLS model was recommended to predict a patient’s w-year dynamic death rate.


Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1130
Author(s):  
Shu-Yein Ho ◽  
Chia-Yang Hsu ◽  
Po-Hong Liu ◽  
Chih-Chieh Ko ◽  
Yi-Hsiang Huang ◽  
...  

Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). The prognostic role of albumin-bilirubin (ALBI) grade in this special setting is unclear. We aimed to investigate the role of ALBI grade associated with the impact of RI on HCC. A prospective cohort of 3690 HCC patients between 2002 and 2016 were retrospectively analyzed. The Kaplan–Meier method and multivariate Cox proportional hazards model were used to determine survival and independent prognostic predictors. Of all patients, RI was an independent predictor associated with decreased survival. In multivariate Cox analysis for patients with RI, α-fetoprotein level ≥20 ng/mL, tumor size >3 cm, vascular invasion, distant metastasis, presence of ascites, performance status 1–2, performance status 3–4, and ALBI grade 2 and grade 3 were independent predictors of decreased survival (all p < 0.05). In subgroup analysis of patients with RI undergoing curative and non-curative treatments, the ALBI grade remained a significant prognostic predictor associated with decreased survival (p < 0.001). In summary, HCC patients with RI have decreased survival compared to those without RI. The ALBI grade can discriminate the survival in patients with RI independent of treatment strategy and is a feasible prognostic tool in this special patient population.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 528-528
Author(s):  
David Mitchell Marcus ◽  
Dana Nickleach ◽  
Bassel F. El-Rayes ◽  
Jerome Carl Landry

528 Background: The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiation followed by surgery, but many physicians question the benefit of multimodality therapy in patients with stage T3N0M0 disease. We aimed to determine the impact of radiation therapy (RT) on overall survival (OS) in this group of patients. Methods: We used the Surveillance, Epidemiology, and End Results database to identify patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum from 2004 to 2010. The Kaplan-Meier method was used to compare OS for patients receiving RT vs. no RT, along with for pre-op vs. post-op RT among patients that received RT. Multivariable analysis (MVA) using a Cox proportional hazards model was performed to assess the association of RT with OS after adjusting for patient age, gender, race, tumor grade, carcinoembryonic antigen, type of surgery, and circumferential margin status. The analysis was repeated separately on patients that underwent total colectomy (TC) vs. sphincter-sparing surgery. Results: The cohort included 8,679 patients, including 4,705 who received RT and 3,974 who did not. Median age was 66 years. Five year OS was 76.5% in patients who received RT, compared to 60.0% in patients who did not receive RT (p <0.001). Five year OS was 76.9% for patients receiving pre-op RT vs. 75.7% in patients receiving post-op RT (p = 0.247). In patients undergoing TC, five year OS was 74.7% for patients receiving RT, compared to 47.5% in patients not receiving RT (p <0.001). In patients undergoing sphincter-sparing surgery, five year OS was 77.7% in patients receiving RT, compared to 62.9% in patients not receiving RT (p <0.001). Use of RT was significantly associated with OS on MVA, both in the entire cohort (HR 0.70 [95% CI 0.60-0.81]; p<0.001) and in subsets of patients undergoing TC (HR 0.55 [95% CI 0.38-0.79]; p=0.001) and sphincter-sparing surgery (HR 0.70 [95% CI 0.59-0.84]; p<0.001). Conclusions: The use of RT is associated with superior OS in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum. This benefit is demonstrated in both the pre-op and post-op settings and applies to patients undergoing both TC and sphincter-sparing surgery.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3139-3139
Author(s):  
Hiroyuki Arai ◽  
Yi Xiao ◽  
Jingyuan Wang ◽  
Francesca Battaglin ◽  
Natsuko Kawanishi ◽  
...  

3139 Background: Protection of replication forks is critical for the survival of cancer cells. Chemotherapeutic drugs such as oxaliplatin and irinotecan can impede the progression of replication forks by inducing DNA lesions, which cause fork collapse and generate double-strand breaks. We hypothesized that functional genetic variants in genes involved in the maintenance of replication forks may predict the efficacy of cytotoxic drugs in mCRC patients. Methods: We analyzed genomic and clinical data from MAVERICC, a phase II trial which compared mFOLFOX6 and FOLFIRI in combination with bevacizumab in untreated mCRC patients. Genomic DNA extracted from blood samples was genotyped using an OncoArray (Illumina, Inc., San Diego, CA, USA). Candidate six missense single nucleotide polymorphisms (SNPs) ( SLFN11 rs9898983, SLFN11 rs12453150, RPA1 rs5030749, MCM3 rs2230240, TIMELESS rs2291739, and TIMELESS rs774047) were tested for association with progression-free survival (PFS) and overall survival (OS), using Cox proportional hazards model. To confirm the predictive value, the treatment-by-SNP interaction was tested. Results: A total of 324 patients were available for the SNP analyses (mFOLFOX6 plus bevacizumab arm [OHP arm]: n = 161; FOLFIRI plus bevacizumab arm [IRI arm]: n = 163). In the OHP arm, univariable analysis showed a significantly better PFS in patients with G/G genotype of TIMELESS rs2291739 compared to those with any A allele, and in patients with T/T genotype of TIMELESS rs774047 compared to those with any C allele. However, neither of these SNP’s associations were confirmed by multivariable analysis: TIMELESS rs2291739 (any A allele vs G/G, hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.31–1.17, p = 0.12) and TIMELESS rs774047 (any C allele vs T/T, HR = 0.74, 95% CI = 0.41–1.36, p = 0.33). In the IRI arm, univariable analysis showed a significantly worse OS in patients with G/G genotype of TIMELESS rs2291739 compared to those with any A allele, and in patients with T/T genotype of TIMELESS rs774047 compared to those with any C allele. Multivariable analysis confirmed the significant associations in these SNPs: TIMELESS rs2291739 (any A allele vs G/G, HR = 3.06, 95% CI = 1.49–6.25, p < 0.01) and TIMELESS rs774047 (any C allele vs T/T, HR = 2.95, 95% CI = 1.43–6.08, p < 0.01). Treatment-by-SNP interaction test confirmed the significant predictive value of both SNPs, both on PFS and OS. Conclusions: Germline polymorphisms in the TIMELESS gene involved in the protection of replication forks may predict efficacy of oxaliplatin and irinotecan in mCRC patients. Our novel findings warrant further validation studies.


2011 ◽  
Vol 96 (4) ◽  
pp. 291-299 ◽  
Author(s):  
Hideyuki Ishida ◽  
Keiichiro Ishibashi ◽  
Tomonori Ohsawa ◽  
Norimichi Okada ◽  
Kensuke Kumamoto ◽  
...  

Abstract The frequency and significance of hepatic lymph node (HLN) metastasis were retrospectively evaluated in 43 patients with unresectable synchronous liver metastasis of colorectal cancer who underwent resection of the primary tumor and histopathologic evaluation of HLNs between March 1997 and August 2007. HLN metastasis was detected in 12 patients (27.9%). No significant correlations were observed between the presence of HLN metastasis and any of the 12 clinicopathologic factors examined. On multivariate analysis using the Cox proportional hazards model, the presence of HLN metastasis (P  =  0.002), along with a large number (≥4) of regional lymph node metastases (P  =  0.003), and nonuse of oxaliplatin-based chemotherapy (P  =  0.005) were identified as independent risk factors for shorter survival. To establish a new therapeutic strategy for initially unresectable liver metastasis of colorectal cancer, HLNs should be examined histologically in patients undergoing resection of hepatic lesions when they are rendered resectable by effective chemotherapy.


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