The need for a revised staging system of metastatic (M) colorectal cancer (CRC): Evidence from a national perspective on survival following surgically treated (HPX) liver metastases

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4099-4099
Author(s):  
E. Morris ◽  
J. Thomas ◽  
D. Forman ◽  
P. Quirke ◽  
B. Cottier ◽  
...  

4099 Background: AJCC V.6 (2002) places all patients with MCRC beyond the lymph node basin of the primary tumor in a homogenous Stage 4. Patients with inoperable hepatic MCRC can be made operable with curative intent with chemotherapy yet remaining in Stage 4. Via the linkage of routine health datasets across England this population-based study sought to determine the impact of HPX for MCRC on stage-matched survival at initial presentation. Methods: All patients between 1998–2001 undergoing surgery for CRC in England were identified via the national-linked cancer registry HES dataset. All care episodes in the 3 years following initial colorectal surgery were examined to determine the frequency of subsequent HPX. Kaplan-Meier curves and log- rank tests were used to examine 5-year survival following HPX for MCRC compared to all Stage 3 and Stage 4 at presentation. Survival was calculated from the date of resection of each patient's primary colorectal tumor. Results: 68,307 individuals were identified as undergoing surgery for primary CRC over the study period. 20,298 were Stage 3 at presentation. 1,483 (2.2%) subsequently underwent HPX <3 years of their colorectal operation. 55 patients died within 30 days of HPX (mortality rate: 3.7%). Crude 5-year survival of patients who underwent HPX was 41.6% (95%CI 39.0–44.1%) from time of initial colectomy. This survival rate was significantly better than that for both Stage 3 (38.6% (95%CI 37.9%-39.2%, P<0.01) and 4 (6.1% 95%CI 5.3–6.9%, P<0.01) overall. Conclusions: 5-year survival following HPX for MCRC is better than that seen overall for all Stage 3 patients (with MCRC confined to the regional draining lymph node basin) following initial colectomy. Our data support the hypothesis that all MCRC that is potentially resectable with curative intent should be stratified within Stage 3, and Stage 4 should only contain those MCRC patients for whom surgery is not an option. If further evidence emerges to support this theory then a revision of the current staging system will be required. [Table: see text]

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 364-364
Author(s):  
Neda Amini ◽  
Yuhree Kim ◽  
Ana Wilson ◽  
Cecilia Grace Ethun ◽  
Shishir Kumar Maithel ◽  
...  

364 Background: The American Joint Committee on Cancer (AJCC) classification is the most universally accepted lymph node (LN) staging system for gallbladder adenocarcinoma (GBA); however, it focuses more on location of LN metastasis than number of LN metastasis. Other lymph node staging systems have been proposed for GBA. We therefore sought to examine the performance of different staging systems including AJCC LN staging system, number of metastatic LN (NMLN), log odds of metastatic LN (LODDS), and LN ratio (LNR). Methods: Patients who underwent curative-intent resection for GBA between 2000 and 2015 and who had lymphadenectomy were identified from a multi-institutional database. The prognostic performance of four staging systems was compared by Harrell’s C and Akaike information criterion (AIC). Results: Overall 214 patients with a median age of 66.7 years (IQR 56.5, 73.1) were identified. A total 1,334 LNs were retrieved from 214 patients, with a median of 4 (IQR 2-8) LNs per patient. In the study cohort, 98 (45.5%) patients had LN metastasis with total of 271 positive LNs [median of 1 (IQR 1-3)]. Patients with LN metastasis had an increased risk of death (HR 1.87, 95%CI 1.24-2.82; P = 0.003). In addition, risk of death increased by each additional LN metastasis (HR 1.20, 95%CI 1.06-1.37; P = 0.005). In the entire cohort, LNR, in either a continuous (C-index: 0.603, AIC: 808.4) or a discrete scale (C-index 0.609, AIC 802.2), provided better discrimination versus LODDS, AJCC LN staging system, and NMLN. The relative performance of all scoring systems was better among patients who had ≥ 4 LN examined. In the cohort of patients with ≥ 4 LN examined, LODDS (C-index 0.621, AIC 363.8) had the best performance compared with LNR (C-index 0.615, AIC 368.7), AJCC LN staging system (C-index 0.601, AIC 373.4), and NMLN (C-index 0.613, AIC 369.5). Conclusions: LODDS and LNR performed better than the AJCC LN staging system. Among those who had more LN examined, LODDS performed better than LNR. LODDS and LNR should be incorporated into the AJCC LN staging system of GBA.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 131-131 ◽  
Author(s):  
Zohra Faiz ◽  
Margreet Van Putten ◽  
Rob H.A. Verhoeven ◽  
Johanna W. van Sandick ◽  
Grard A. P. Nieuwenhuijzen ◽  
...  

131 Background: Surgery after neoadjuvant chemoradiotherapy (nCRT) is the most common treatment with curative intent for esophageal cancer (EC) patients. Definitive chemoradiotherapy (dCRT) is an alternative for patients who are not eligible for resection because of comorbidity. The purpose of this retrospective study was to evaluate patient and tumor characteristics which are associated with the type of treatment. Methods: We selected all consecutive patients with a locally advanced EC (cT1 N + / T2-3N0-3M0-1a) who were treated with curative intent (nCRT, dCRT or surgery only) in the South East Netherlands between 1995 and 2013. For a proper assessment of the impact of co-morbidity, T4 tumors were excluded. The effect of co-morbidity on treatment decision and on survival was analyzed using a multivariable logistic regression and Kaplan-Meier method. Survival time was defined as time from 6 months after diagnosis until death or until January 1st 2015 for patients who were still alive. Results: Of the 1098 patients, surgery only was performed in 46%, nCRT in 28% and dCRT in 26%. Patients with ≥ 2 co-morbidities underwent more frequently dCRT (OR = 2.35; 95% CI: 1.45-3.86), or resection only (OR = 2.29; 95% CI: 1.41-3.69). Patients > 75 years (OR = 6.66; 95% CI: 3.48-12.77), patients with hypertension and diabetes (OR: 4.05;95% CI: 1.96-8.37-3.90) and patients with cardiovascular (mostly myocardial infarction) and pulmonary comorbidity (OR = 3:33; 95% CI: 1:51 to 7:34) underwent frequently more dCRT than nCRT. Patients with esophageal squamous cell carcinoma (ESCC) also had more frequently dCRT (OR = 2.27; 95% Cl: 1.38-3.73). Patients with an adenocarcinoma and ≥ 2 co-morbidities had favorable 3-year overall survival (OS) after nCRT compared with dCRT and surgery alone (p < 0.01). However, the 3-year OS after nCRT was similar after dCRT in ESCC patients with ≥ 2 co-morbidities (p = 0.75). Conclusions: The results of this study support the treatment with dCRT in patients with SCC of the esophagus, and with at least two co-morbidities, in particular, the combination of cardiovascular / pulmonary disorders and hypertension plus diabetes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Honghu Wang ◽  
Hao Qi ◽  
Xiaofang Liu ◽  
Ziming Gao ◽  
Iko Hidasa ◽  
...  

AbstractThe staging system of remnant gastric cancer (RGC) has not yet been established, with the current staging being based on the guidelines for primary gastric cancer. Often, surgeries for RGC fail to achieve the > 15 lymph nodes needed for TNM staging. Compared with the pN staging system, lymph node ratio (NR) may be more accurate for RGC staging and prognosis prediction. We retrospectively analyzed the data of 208 patients who underwent R0 gastrectomy with curative intent and who have ≤ 15 retrieved lymph nodes (RLNs) for RGC between 2000 and 2014. The patients were divided into four groups on the basis of the NR cutoffs: rN0: 0; rN1: > 0 and ≤ 1/6; rN2: > 1/6 and ≤ 1/2; and rN3: > 1/2. The 5-year overall survival (OS) rates for rN0, rN1, rN2, and rN3 were 84.3%, 64.7%, 31.5%, and 12.7%, respectively. Multivariable analyses revealed that tumor size (p = 0.005), lymphovascular invasion (p = 0.023), and NR (p < 0.001), but not pN stage (p = 0.682), were independent factors for OS. When the RLN count is ≤ 15, the NR is superior to pN as an important and independent prognostic index of RGC, thus predicting the prognosis of RGC patients more accurately.


Author(s):  
Subbiah Shanmugam ◽  
Gopu Govindasamy ◽  
X. Gerald Anand Raja

<p class="abstract"><strong>Background:</strong> Depth of invasion is included in the staging of oral cavity malignancies in the recent 8<sup>th</sup> edition of American Joint Committee on Cancer or tumour, node and metastasis staging system. This study analyses the impact of diffuse optical imaging (DOI) on incidence of lymph node involvement, stage migration, postoperative margin and independency.</p><p class="abstract"><strong>Methods:</strong> Postoperative HPE of fifty patients with oral cavity malignancy operated in our institute from January 2018 were collected. Depth of invasion and other pathological parameters were documented. DOI divided into three groups and statistical analysis done.  </p><p class="abstract"><strong>Results:</strong> No lymph node metastasis is found in superficial tumours, 43% of intermediate thickness and 76% of deep tumours had lymph node involvement. Positive margin is seen only in patients with tumour DOI more than 0.5 cm, more than 50% of deep tumours had close margins while 75% of superficial tumours had adequate margin. Out of the 24 T3 tumours in this study 13 were upstaged due to inclusion of DOI, which would have been T2 according to the previous staging system. There is 54.1% (13 out of 24) upstaging in T3 tumours (T2 to T3), 23% (3 out of 13) in T2 (T1 to T2). There is no significant correlation between DOI and anatomical site, tumour size, tumour thickness, lymphovascular invasion and grade.</p><p class="abstract"><strong>Conclusions:</strong> Depth of invasion in oral cavity malignancies impacts adversely lymph node metastasis and margin status. It is an independent prognostic factor in oral cavity malignancy.</p>


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1613-1613 ◽  
Author(s):  
Megan Othus ◽  
Mikkael A Sekeres ◽  
Sucha Nand ◽  
Guillermo Garcia-Manero ◽  
Frederick R. Appelbaum ◽  
...  

Abstract Background: CR and CR with incomplete count recovery (CRi) are associated with prolonged overall survival (OS) for acute myeloid leukemia (AML) patients (pts) treated with curative-intent, induction therapy. For AML pts treated with azacitidine (AZA), response (CR, partial response, marrow CR, or hematologic improvement) is also associated with prolonged OS. We evaluate whether patients given AZA for myelodysplastic syndromes (MDS) or AML had longer OS if they achieved CR. We also compare the effect size of CR on OS between AZA regimens and 7+3. Patients and Methods: We analyzed four SWOG studies: S1117 (n=277) was a randomized Phase II study comparing AZA to AZA+lenalidomide or AZA+vorinostat for higher-risk MDS and CMML pts (median age 70 years, range 28-93); S0703 (n=133) treated AML pts not eligible for curative-intent therapy with AZA+mylotarg (median age 73 years, range 60-88). We analyzed the 7+3 arms of S0106 (n=301 were randomized to 7+3, median age 48 years, range 18-60) and S1203 (n=261 were randomized to 7+3, median age 48 years, range 19-60). CR was defined per 2003 International Working Group criteria. In S1117 CR was assessed every 16 weeks and patients remained on therapy until disease progression. In S0703, S0106, and S1203 CR was assessed following 1-2 induction cycles; patients not achieving CR (S0106) or CRi (S0703 and S1203) were removed from protocol treatment. OS was measured from date of study registration. To avoid survival by response bias, we performed landmark analyses of OS. We present results based on the study-specific landmark date that 75% of pts who eventually achieved a CR had done so (S1117 144 days, S0703 42 days, S0106 44 days, S1203 34 days). Pts who did not achieve CR by this date were analyzed with pts who never achieved CR. Pts who died or were lost to follow-up before this date were excluded from analyses. As a sensitivity analysis we also analyzed based on the 90% date; results were not materially different. Log-rank tests were used to compare survival curves and Cox regression models were used for multivariable modeling including baseline prognostic factors age, sex, performance status, white blood cell count, platelet count, marrow blast percentage, de novo disease (versus antecedent MDS or therapy-related disease), study arm (for S1117 only), and cytogenetic risk (IPSS criteria for S1117, SWOG criteria for S0703, S0106, and S1203). The following analysis considers morphologic CR only. S0106 treated CR with incomplete count recover (CRi) pts as treatment failures (S0703 and S1203 did not) and CRi was not defined for S1117. Hematologic improvement was only defined for S1117 patients. Results: In univariate analysis, CR was significantly associated with prolonged survival among MDS pts treated with azactidine on S1117 (HR=0.55, p=0.017), confirming the results seen in AML pts treated with azacitidine (and mylotarg, S0703, HR=0.60, p=0.054) and 7+3 (S0106 HR=0.44, p<0.001; S1203 HR=0.32, p<0.0001) (Figure 1). For each study this relationship remained significant in multivariable analysis controlling for baseline prognostic factors (S1117 HR=0.25, p<0.001; S0703 HR=0.64, p=0.049; S0106 HR=0.45, p<0.001; S1203 HR=0.41, p<0.001). There was no evidence that the impact of CR varied across the four cohorts (interaction p-value = 0.76). In the full cohort, the effect of CR was associated with a HR of 0.45 (Table 1). Conclusion: Adjusting for pt characteristics, achievement of morphologic CR was associated with a 60% improvement in OS, on average, compared to that seen in pts who don't achieve a CR, regardless of whether pts were treated with 7+3 or AZA containing regimens, and suggesting that value CR is similar of whether pts receive more or less "intensive" therapy for these high grade neoplasms. Support: NIH/NCI grants CA180888 and CA180819 Acknowledgment: The authors wish to gratefully acknowledge the important contributions of the late Dr. Stephen H. Petersdorf to SWOG and to study S0106. Figure 1 Kaplan-Meier plots of landmark survival by response. Figure 1. Kaplan-Meier plots of landmark survival by response. Table 1 Multivariable analysis, N=878 Table 1. Multivariable analysis, N=878 Disclosures Othus: Glycomimetics: Consultancy; Celgene: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees. Erba:Millennium Pharmaceuticals, Inc.: Research Funding; Amgen: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Agios: Research Funding; Gylcomimetics: Other: DSMB; Juno: Research Funding; Daiichi Sankyo: Consultancy; Sunesis: Consultancy; Pfizer: Consultancy; Ariad: Consultancy; Jannsen: Consultancy, Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Celator: Research Funding; Astellas: Research Funding; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 165-165
Author(s):  
Michael J. McNamara ◽  
Lisa A. Rybicki ◽  
Cristina P. Rodriguez ◽  
Gregory M.M. Videtic ◽  
Kevin L. Stephans ◽  
...  

165 Background: A complete pathologic response to induction CRT has been identified as a favorable prognostic factor for patients with LRA ACA of the E/GEJ. Less is known, however, about the impact of pathologic regression after induction chemotherapy. Methods: Between 2/08 and 1/12, 60 evaluable patients with ACA of the E/GEJ enrolled in a phase II trial of induction chemotherapy, surgery, and post-operative CRT. Eligibility required a clinical stage of T3 or N1 or M1a (AJCC 6th). Induction chemotherapy with epirubicin 50mg/m2 d1, oxaliplatin 130mg/m2 d1, and fluorouracil 200mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55Gy @ 1.8-2.0 Gy/d and 2 courses of cisplatin (20mg/m2/d) and fluorouracil (1000mg/m2/d) over 4 days during weeks 1 and 4 of radiotherapy. RV was defined as the amount of remaining tumor in relation to acellular mucin pools and scarring. Results: Of the 60 evaluable patients, 54 completed induction therapy and underwent curative intent surgery. The Kaplan-Meier (KM) projected 3 year OS for patients with pathologic N0 (n=20), N1 (n=12), N2 (n=13), and N3 (n=9) disease is 73%, 57%, 35%, and 0% respectively (p<0.001). The KM projected 3 year OS of patients with low (0-25%, n=19), intermediate (26-75%, n=26), and high (>75%, n=9) RV was 67%, 42%, and 17% respectively (p=0.004). On multivariable analysis, both the pN descriptor and RV were independently prognostic for OS. In patients with less nodal dissemination (N0/N1), RV was prognostic for OS [3yr OS 85% (0-25% viable) v 51% (>25% viable), p=0.028]. Outcomes were poor, however, for patients with advanced nodal disease (N2/N3) regardless of RV [3yr OS 20% (0-25% viable) v 21% (>25% viable), p=0.55]. Conclusions: RV and the pN descriptor after induction chemotherapy are independent pathologic prognostic factors for OS in patients with LRA ACA of the E/GEJ. Patients with extensive nodal disease, however, have poor outcomes irrespective of viability. Clinical trial information: NCT00601705.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3613-3613
Author(s):  
Shiru Lucy Liu ◽  
Pierre O'Brien ◽  
Yizhou Zhao ◽  
Wilma M Hopman ◽  
Nathan William Dana Lamond ◽  
...  

3613 Background: Little is known about the benefit and use of adjuvant chemotherapy (ADJ) in the elderly population (age ≥ 65) with locally advanced rectal cancer (LARC). We undertook a provincial review of LARC patients to evaluate the potential benefits, including survival and time to relapse (TTR), of ADJ in elderly patients. Methods: We performed a retrospective analysis of 286 LARC patients (stage 2 and 3) diagnosed between January 2010 and December 2013 from Nova Scotia, Canada, who underwent curative-intent surgery. Baseline patient, tumor and treatment characteristics were collected. Survival and TTR analysis were performed using Kaplan-Meier and Cox-regression statistics. Results: 152 patients were age ≥65, and 92 age ≥70. Median follow-up was 46 months. 178 patients (62%) received neoadjuvant chemo-radiation (NEOADJ). While 109 patients (81%) age < 65 received ADJ, only 68 patients (45%) age ≥ 65 received ADJ. Kaplan-Meier analysis revealed a significant survival and TTR advantage for ADJ irrespective of age (table). In cox-regression multivariate analysis, ECOG status, T stage, and ADJ were significant predictors of survival (p < 0.04), while age was not. Similarly, N stage, NEOADJ, and ADJ were significant predictors of TTR (p < 0.007). Poor ECOG status was the most common cause of ADJ omission. There was a significantly higher amount of grade≥ 1 chemotherapy-related toxicity experienced by patients age ≥ 65 treated with ADJ compared to no ADJ (77% vs 32%, p < 0.0001), which consisted mostly of diarrhea and mucositis. Toxicity was the main reason for non-completion of ADJ in the elderly. Conclusions: Elderly patients with LARC have significantly improved overall survival with ADJ, but the use of ADJ is lower than in patients age < 65. However, elderly patients experience more chemotherapy-related toxicities, leading to higher rates of early treatment discontinuation. [Table: see text]


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 682-682
Author(s):  
Brian Cox ◽  
Nicholas Manguso ◽  
Humair Quadri ◽  
Jessica Crystal ◽  
Katelyn Mae Atkins ◽  
...  

682 Background: Lymph node (LN) metastases affect overall survival (OS) in pancreatic cancer (PC). However, a LN sampling threshold does not exist. We examined the impact of nodal sampling on overall survival (OS). Methods: Patients with Stage I-III PC ≥55 years old who underwent curative resection from 2004-2016 were identified from the National Cancer Database (NCDB). After adjusting for age, gender, grade, stage, and Charlson-Deyo score, multiple binomial logistic regression analyses assessed the impact of the LN ratio (LNR) on OS. LNR was defined as the number of positive LN over the number of LN examined. Regression analyses, a Cox-Regression, and a Kaplan-Meier survival curve assessed how many LN should be sampled. Results: A total of 13,673 patients, median age 69 years (55-90), were included. Most were Caucasian (86.6%) males with Charlson-Deyo scores ≤ 1 (90.3%) and moderately to poorly differentiated PC (90.1%). Median number of LN examined was 15 (1-75) with a median of 1 positive LN (0-35). As expected, increased number of positive LNs was associated with reduced OS, p < 0.001. After data normalization, an increasing LNR was associated with a 12-fold likelihood of death [OR: 11.9, p < 0.001 (CI 6.0, 23.7)]. Subsequent regression models established evaluation of ≥ 16 LNs as the greatest predictor of OS. A regression model evaluating < or ≥ 16 lymph nodes was performed to ascertain the effects of age, gender, ethnicity, grade, stage, and LN examined on OS. The logistic regression model correctly classified 74.5% of cases with a specificity of 99.6% (p < 0.001). Examination of < 16 LN, Caucasian race, grade, stage, and higher Charlson-Deyo scores were significantly associated with decreased OS. If ≥ 16 LNs were examined, patients had a 1.5-fold likelihood of better OS, p < 0.001 (CI 1.4, 1.6). An adjusted Cox Regression showed increased HR of 1.2, p < 0.001 (CI 1.1, 1.2) and an unadjusted Kaplan Meier survival curve predicted ≥ 16 LN examined are associated with an increase in OS of 2.8 months [log-rank: 32.0, p < 0.001]. Conclusions: Patients undergoing curative intent resection for PC should have adequate nodal sampling. Stratification of patients by LNR may provide useful information of OS. Examination of ≥ 16 LNs impacts OS in patients with Stage I-III PC.


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