Prognostic Value of Nodal Response After Preoperative Treatment of Gastric Adenocarcinoma

Background: Pathologically positive lymph nodes (ypN+) after preoperative chemotherapy are associated with poor survival in patients with gastric cancer. Little is known about the association between response to preoperative therapy and the benefit of postoperative therapy. Methods: This retrospective cohort study of the National Cancer Database included patients with clinically node-positive (cN+) gastric cancer treated with preoperative therapy followed by surgery (2006–2014). Preoperative treatment modality was categorized as the inclusion of radiation therapy (RT) or chemotherapy alone. Pretreatment clinical and pathologic stages were used to determine pathologic treatment response rates. The association between overall risk of death and preoperative treatment, disease response, and adjuvant therapy use was evaluated using multivariable Cox regression. Results: Preoperative RT was used in 53.6% of 1,976 patients with cN+ gastric cancer, (74.3% cardia and 10.1% noncardia). The nodal response rate was 38.9% and was higher with RT than with chemotherapy alone (cardia, 46.0% vs 29.1%; P<.001; noncardia, 43.8% vs 31.9%; P=.06). Preoperative RT was associated with an approximate 2-fold increase in the odds of pathologic response compared with chemotherapy. Overall, use of adjuvant therapy was not associated with a decreased risk of death. A primary tumor response with residual nodal disease was not associated with survival (hazard ratio [HR], 1.03; 95% CI, 0.66–1.60). However, a nodal response with residual primary disease was significantly associated with survival (HR, 0.54; 95% CI, 0.44–0.65). Conclusions: More than one-third of node-positive gastric cancers showed pathologic nodal response with preoperative treatment. RT is associated with a higher response than chemotherapy. Patients with ypN+ disease have worse survival, regardless of whether they receive postoperative therapy. Future gastric cancer trials should evaluate the role of preoperative RT and individualize postoperative therapy use.

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Pathologic nodal response in gastric cancer: Do all patients need adjuvant therapy?

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.107 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 107-107

Author(s):

Brandon George Smaglo ◽

Yvonne Sada ◽

Hop Sanderson Tran Cao ◽

Mehmet Akce ◽

Henry Mok ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Therapy ◽

Median Survival ◽

Cox Regression ◽

Multivariable Analysis ◽

Treatment Sequence ◽

Disease Response ◽

Risk Of Death ◽

Pre Treatment ◽

Chemotherapy Patients

107 Background: Recent data from the MAGIC trial show that pathologically positive lymph nodes (ypN+) despite neoadjuvant (NA) chemotherapy are associated with poorer survival. Although the use of NA therapy has increased, pathologic disease response to multimodality therapy (MMT) and its impact on outcome have not been well-defined. Methods: This retrospective cohort study of the National Cancer Database included patients with cN+ gastric cancer who underwent NA therapy followed by surgical resection between 2006 and 2012. Patients were categorized by NA treatment (chemotherapy or concurrent chemoradiation). Pre-treatment clinical (cN) and pathologic nodal staging (ypN) were used to determine downstaging rates from cN+ to ypN0. The association between overall risk of death and NA treatment, nodal response, and the use of adjuvant therapy was evaluated with multivariable Cox regression. Results: Among 1,489 patients with cN+ gastric cancer receiving NA therapy, 45.5% were treated with chemotherapy and 54.5% with chemoradiation. Rates of nodal downstaging were 29.9% for chemotherapy and 45.4% for chemoradiation. On multivariable analysis, treatment sequence and type were not associated with risk of death. Median survival was significantly lower in patients with ypN+ compared to those with ypN0 disease (27.7 vs 79.7 months; log-rank, p < 0.001).Among patients with ypN+ disease (n = 918), median survival was greater if adjuvant therapy was received (32.6 months vs. 25.3 months, log-rank, p < 0.001); adjuvant therapy was associated with a 19% decreased risk of death (Hazard Ratio [HR] 0.81; 95% CI 0.66-0.99), with further reduction among those who underwent a margin negative resection (HR 0.73; 95% CI 0.58-0.92). In patients with ypN0, adjuvant therapy was not associated with a lower risk of death. Conclusions: Over one third of node-positive gastric cancers demonstrated pathologic nodal downstaging with NA treatment, with chemoradiation yielding a higher response than chemotherapy. Patients with ypN+ had worse survival, and appeared to benefit from adjuvant therapy. Future gastric cancer trials should better define the role for NA chemoradiation and help individualize the use of adjuvant therapy based on nodal response.

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Outcomes of adjuvant chemoradiotherapy after a radical gastrectomy and D2 node dissection for gastric adenocarcinoma in INEN (Lima, Peru).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.150 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 150-150

Author(s):

Paola Catherine Montenegro ◽

Lourdes Lopez ◽

Shirley Quintana ◽

Luis Augusto Casanova ◽

Victor Castro ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Therapy ◽

Gastric Adenocarcinoma ◽

Curative Resection ◽

Standard Treatment ◽

Adjuvant Chemoradiotherapy ◽

Rank Test ◽

D2 Lymphadenectomy ◽

Risk Of Death ◽

Node Positive

150 Background: Adjuvant chemoradiotherapy is the standard treatment in Western countries in gastric cancer patients submitted to curative resection. INT 0116 pivotal trial established adyuvant chemoradiation as the standar care for resected high risk adenocarcionoma of the stomach in US however was hampered by suboptimal surgery. There is controversial data about efficacy of this adjuvant therapy in patients who have undergone D2 lymphadenectomy predominantly. In our hospital D2 lymphadenectomy is standar surgery for gastric cancer. Methods: Retrospective study with gastric adenocarcinoma patients stage II to IV M0 who underwent curative resection at Instituto Nacional de enfermedades Neoplasicas Lima- Peru between 2001 and 2006 Standard treatment at institution is D2 lymphadenectomy. Chemoradiotherapy according to INT 0116 was given like adjuvant therapy. Survival curves were calculated according to Kaplan-Meier method and compared with log-rank test. Multivariate analysis of prognostic factors related to survival was performed by Cox proportional hazards model adjusted for age, stage and adjuvant chemoradiotherapy. Results: 84 patients were included 60.3% male and 39.3% female. Median age was 40.5 years old. The patologic stage were T1-T2 (12.3%), T3-T4 ( 50% ), N0-N1 (10.7%), N2-N3 (89.3%). D2 lymphadenectomy was performed in all patients. The 3-year DFS was 17% and 3-year overall survivall was 23.9% years.However when we analized by subgroups the overal survival was significantly longer in group N1 ( 61%) and N2 (58.9%) that N3 (18.3%) and DFS were N1 (60%), N2 (55%) and N3 (16.3%). Conclusions: Adjuvant chemoradiotherapy decreased risk of death and relapse in patients with node positive N1-N2 , who underwent curative resection with D2 lymphadenectomy, but recurrence was most frecuent in N3 node positive, maybe is necesary improve the chemotherapy in this group of patientes for dicrease the rate of relapse.

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The prognostic value of signet ring cell histology in resected gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.128 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 128-128 ◽

Cited By ~ 1

Author(s):

Lauren McLendon Postlewait ◽

Malcolm Hart Squires ◽

David A. Kooby ◽

George A. Poultsides ◽

Sharon M. Weber ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Therapy ◽

Cox Regression ◽

Preoperative Evaluation ◽

Signet Ring Cell ◽

Tnm Stage ◽

Specific Analysis ◽

Pathologic Features ◽

Signet Ring ◽

Ring Cell

128 Background: Conflicting data exist on the prognostic implication of signet ring cell (SRC) histology in gastric adenocarcinoma (GAC). Our aim was to assess the association of SRC with recurrence and survival in patients undergoing resection of GAC. Methods: All pts who underwent curative intent resection for GAC from 2000 to 2012 at 7 academic institutions comprising the US Gastric Cancer Collaborative were included. 30-day mortalities were excluded. Survival analyses included Kaplan Meier log rank and multivariate Cox regression. Primary endpoints were recurrence-free survival (RFS) and overall survival (OS). Stage-specific analysis was performed. Results: Of 965 pts, 768 met inclusion criteria. SRC was present in 39.5% and was associated with female gender (52.9% vs 38.6%; p<0.001), younger age (61 vs 67 yrs; p<0.001), poor differentiation (94.8% vs 50.3%; p<0.001), perineural invasion (PNI: 41.4% vs 23%; p<0.001), distal location (82.2% vs 70.1%; p<0.001), receipt of adjuvant therapy (63% vs 51.2%; p=0.002), and more advanced stage (Stage 3: 55.2% vs 36.5%; p<0.001). SRC was associated with earlier recurrence (56.7mo vs median not reached (MNR); p=0.009) and decreased OS (33.7mo vs 46.6mo; p=0.011). When accounting for other adverse pathologic features, PNI (HR 1.57; p=0.016) and higher TNM stage (HR 2.63; p<0.001) were associated with decreased RFS, but SRC was not. PNI (HR 1.53; p=0.006), higher TNM Stage (HR 2.10; p<0.001), greater size (HR 1.05; p=0.014), and adjuvant therapy (HR 0.50; p<0.001) were associated with OS. SRC was not an independent predictor of OS. Stage-specific analysis showed no association between SRC and RFS or OS in Stage 1 or 3. In Stage 2, SRC was associated with earlier recurrence (38.1mo vs MNR; p=0.005) but not OS. The negative association of SRC with decreased RFS persisted in multivariate analysis (HR 3.11; p=0.015). Conclusions: Signet ring histology is associated with other adverse pathologic features including higher grade and higher TNM stage but is not independently associated with reduced RFS or OS. Identification of signet ring histology during preoperative evaluation should not, in isolation, dictate treatment strategy.

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Prognostic value of Ki-67 in patients with hypertension and prostate cancer: A real-world study in a Chinese population

10.21203/rs.2.21104/v1 ◽

2020 ◽

Author(s):

Zhijun Cao ◽

Mengqi Xiang ◽

Zhiyu Zhang ◽

Jianglei Zhang ◽

Minjun Jiang ◽

...

Keyword(s):

Prostate Cancer ◽

Prognostic Value ◽

Cox Regression ◽

Cox Model ◽

Prognostic Nutritional Index ◽

Fold Increase ◽

Lasso Regression ◽

Ki 67 ◽

Risk Of Death ◽

Risk Of Progression

Abstract Background Prostate cancer is the second most common malignancy in males worldwide, with high mortality, especially when combined with hypertension. Ki-67 is one of the most reliable markers of growth for neoplastic human cell populations. However, the prognostic value of Ki-67 in patients with hypertension and prostate cancer remains unclear.Methods We retrospectively analyzed 296 patients with hypertension and prostate cancer from May 1, 2012, to October 1, 2015. The overall survival was evaluated by Cox regression models and Kaplan-Meier analysis. In addition, a nomogram was established, and the accuracy of the model was assessed by a calibration curve.Results A total of 101 (34.1%) patients died. In the multivariate analysis, being Ki-67(+) was associated with a >5-fold increase in the risk of death (hazard ratio [HR] 5.83, 95% confidence interval [CI] 3.35-10.14, p<0.001) and a 2-fold increase in the risk of progression (HR 2.06, 95% CI 1.37-3.10, p<0.001). Multivariate Lasso regression showed that smoking, heart failure, ACS, Ki-67 expression, serum albumin, prognostic nutritional index, surgery, Gealson score, and stage were positively associated with prognosis in patients with prostate cancer. To quantify the contribution of each covariate to the prognosis, a nomogram of the Cox model was generated. The nomogram demonstrated excellent accuracy in estimating the risk of death, with a bootstrap-corrected C index of 0.829. There was also a suitable calibration curve for risk estimation.Conclusions The presence of Ki-67 predicts worsened outcomes for overall mortality. A cross-validated multivariate score including Ki-67 had excellent concordance and efficacy for predicting prostate cancer.

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Parametric Model Evaluation in Examining the Survival of Gastric Cancer Patients Andits Influencing Factors

Global Journal of Health Science ◽

10.5539/gjhs.v9n3p260 ◽

2016 ◽

Vol 9 (3) ◽

pp. 260

Author(s):

Abolfazl Nikpour ◽

Jamshid Yazdani Charati ◽

Iraj Maleki ◽

Hosien Ranjbaran ◽

Alireza Khalilian

Keyword(s):

Gastric Cancer ◽

Survival Data ◽

Cox Regression ◽

Weibull Model ◽

Exponential Model ◽

Study Data ◽

Parametric Models ◽

Risk Of Death ◽

Log Normal ◽

Gastric Cancer Patients

BACKGROUND: Cox proportional hazard model is the most common technique to analysis the variables effect on survival time, but under certain circumstances, parametric models may offer advantages over Cox’s model. In this study we use cox regression and alternative parametric models such as Weibull, exponential, log-normal, logistics and gamma model to evaluate factors affecting survival of patients with gastric cancer. Comparisons were made to find the best model.METHOD: In this study, data from 643 patients with gastric cancer who were referred to Imam Khomeini hospital with personal details during 2007 to 2013 have been reviewed in order to determine the survival rate of gastric cancer. It was observed that 74 cases were eliminated due to incomplete information and 569 persons were examined. Akaike Information model was used for comparison between models.RESULT: Of a total of 569 patients, 329 (57.8%) died during the period. The figure of Cox-Snell residuals indicates that only the exponential model does not have better fitness. Weibull, log-normal, log-logistic and gamma models show the better fitness because points are on straight line. At the time of diagnosis, stage with (p<0.0008) and metastasis with (p<0.0219) were subjected to higher risk of death.CONCLUSION: Based on Akaike's criterion, the Weibull model with Akaike value of 257.165 is the most favorable for survival data.

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HAGE (DDX43) protein expression as an independent biomarker of poor clinical outcome of breast cancer (BC) and potential as a therapeutic target for ER-negative BC.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1013 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1013-1013 ◽

Cited By ~ 1

Author(s):

Stephen Chan ◽

Tarek M. A. Abdel-Fatah ◽

Stephanie McArdle ◽

Paul Moseley ◽

Catherine Johnson ◽

...

Keyword(s):

High Risk ◽

Clinical Outcome ◽

Protein Expression ◽

Cox Regression ◽

Positive Impact ◽

Prospective Trial ◽

Fold Increase ◽

Distant Metastases ◽

Poor Clinical Outcome ◽

Risk Of Death

1013 Background: Recently, we have confirmed that HAGE is involved in promoting proliferation as assessed by increased thymidine incorporation and our preliminary results using shRNA to permanently knockdown HAGE expression also suggests the involvement of HAGE in tumor motility and metastasis. In this study we aimed to analyze the expression of HAGE in large well-characterized BC cohorts to determine its relationship with other clinico-pathological parameters and to investigate its prognostic value. Methods: HAGE protein expression was assessed in: a) 40 normal breast tissue (NBT), b) 60 invasive BCs and their matching NBT, c) BC cell lines, d) A series of 1650 consecutive cases of primary BC who treated with adjuvant CMF and/or endocrine therapies. Further validation was performed in 2 independent series of high risk ER- BC: a) 300 ER –BC who did not received any CT and b) 396 ER- BC treated with adjuvant anthracycline (ATC) based CT. Results: The NBT showed negative HAGE expression (HAGE-) throughout. HAGE overexpression (HAGE+) was observed in 10% of BC and was significantly associated with aggressive clinico-pathological features including: ER-, high grade and triple negative phenotypes. Moreover, HAGE+ expression showed an adverse outcome with a 2-4 fold increase in the risk of death, recurrence and metastases (ps<0.00001) compared to HAGE-; ps<0.0001. Using a multivariate Cox regression model including ER status, grade, size and tumour stage, HAGE expression was confirmed as a powerful independent prognostic factor (p<0.0001). The poor clinical outcome of HAGE+ was further confirmed in high risk (NPI>3.4) ER- patients who did not received any CT (p<0.0001). While, adjuvant CT either CMF or ATC had a positive impact on HAGE+/high risk ER- BC as HAGE+ had a similar risk of death, recurrence and distant metastases to HAGE- expression. Conclusions: This is the first report which shows HAGE to be a potential predictor for poor prognosis in BC patients, and may be an attractive novel target for molecular and vaccine therapy for those patients. A prospective trial of adjuvant chemotherapy/vaccine to confirm this finding is warranted.

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Does in-house availability of multidisciplinary teams increase survival in upper GI cancer?

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4066 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 4066-4066

Author(s):

Christian Kersten ◽

Milada Cvancarova ◽

Geir Boehler ◽

Svein Mjaaland ◽

Odd Mjaaland

Keyword(s):

Cox Regression ◽

Survival Rates ◽

Fold Increase ◽

Primary Objective ◽

Multidisciplinary Teams ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Pancreatic Cancers ◽

Administrative Institution ◽

Upper Gi Cancer

4066 Background: Treatment of esophageal, gastric and pancreatic cancers (UGI) is recommended to be discussed by a multidisciplinary team (MDT), despite lack of evidence that this approach leads to increased survival. In 2001, a cancer centre with irradiation and chemotherapy facilities was established in the Norwegian county of West Agder (WA), providing the potential for local in-house MDT meetings. Our primary objective was to evaluate the effect of the establishment of in-house MDT availability (iMDTa) on survival in a cohort of UGI patients in WA. We compared survival figures for WA with those of other Norwegian counties with complete, less complete and without iMDTa. Methods: We defined “iMDTa” as a single administrative institution with all departments on one campus, serving the population of one county. We compared cause-specific survival rates for 2000-04 and 2005-08 for UGI patients living in counties with (MDT-Yes), without (MDT-No) and with a mix (MDT-mix) of iMDTa, with the county of WA which had a change in iMDTa (MDT-Change) during the study period. Crude survival was modelled with Kaplan-Meier method and Cox regression analysis was used to adjust for age and region (sex and stage distributions were similar in all counties). Results: We analyzed 12530 UGI patients living in five Norwegian regions. Median age was 74 (17-98) yrs and median follow-up was 5 (0-138) months. The regions with the highest level of iMDTa achieved the largest increases in survival, compared to the counties with limited or no iMDTa. Median overall survival for all UGI patients in WA/MDT-Change increased from 129 to 300 days from 2000-8, p=0.001. Compared to the county with MDT-Mix, the county with MDT-Change reached a statistically significant reduction in the risk of death (HR) for both esophageal (1.12- 0.60) and stomach cancers (0.87-0.63), but not for pancreatic cancers (1.04-1.01). Conclusions: In parallel with an increasing use of in-house MDT, we found a striking and more than two-fold increase in survival in the Norwegian county of WA/MDT-Change. This survival gain is partly explained by increased use of chemotherapy. During the same time period, no increase in survival was found in the MDT-No or MDT-Mix counties.

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Preoperative therapy for gastric adenocarcinoma in relation to oncologic outcomes in patients with complications after gastrectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.107 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 107-107

Author(s):

Diego Vicente ◽

Naruhiko Ikoma ◽

Y. Sabrina Chiang ◽

Keith Fournier ◽

Paul F. Mansfield ◽

...

Keyword(s):

Gastric Cancer ◽

Cox Regression ◽

Negative Impact ◽

Multivariable Analysis ◽

Disease Free Survival ◽

Preoperative Therapy ◽

Oncologic Outcomes ◽

Interaction Terms ◽

Disease Mortality ◽

The Impact

107 Background: Postoperative complications (POC) are associated with poor oncologic outcomes in gastric cancer, however, it is unknown if preoperative therapy has any impact on this association. We sought to evaluate the impact of POC on survival in patients with gastric cancer treated with upfront surgery versus those treated with preoperative therapy. Methods: We analyzed data from a prospectively maintained database of patients who had undergone resection of their gastric cancer at our institution between 1995 and 2015. Patients with T1N0 or M1 lesions, recurrent disease, mortality within 90 days, and GEJ tumors were excluded. Cox regression analyses were used to examine factors associated with overall survival (OS) and disease free survival (DFS). Interaction terms between complications and preoperative therapy were used in the multivariate model to determine their impact on OS and DFS. Results: 421 patients underwent resection of gastric cancer: 30% underwent upfront surgery, and 51% had a POC. Variables associated with POCs included total gastrectomy (p = 0.02) and additional organ resection (p = 0.05). Among patients who had POCs, 71% were infectious, 41% experienced multiple complications, and 55% were classified as Clavien-Dindo grade III or IV. On multivariable analysis, the presence of a POC had the strongest association with diminished OS (HR 3.5, 95% CI 1.9-6.5). Among patients who underwent upfront surgery, patients with a POC had shorter OS (5-year, 85% vs. 47%; p < 0.001) and DFS (5-year, 76% vs. 46%; p < 0.001) than those without a POC. In contrast, there was no difference in OS (5-year, 63% vs. 57%; p = 0.77) and DFS (5-year, 52% vs. 52%; p = 0.52) between patients with and without POC who received preoperative therapy. Interaction terms between preoperative therapy and complication in the multivariable Cox regression model were significant on OS (3.53 [95%CI: 1.92-6.52]) and DFS (2.84 [95%CI: 1.59-5.08]), which indicated that the negative impact of complications were reduced if patients received preoperative therapy. Conclusions: The use of preoperative therapy negated the impact of POCs on OS and DFS in patients undergoing resection for gastric cancer.

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Combined Neutrophil-to-Lymphocyte and Platelet-Volume-to-Platelet Ratio (NLR and PVPR Score) Represents a Novel Prognostic Factor in Advanced Gastric Cancer Patients

Journal of Clinical Medicine ◽

10.3390/jcm10173902 ◽

2021 ◽

Vol 10 (17) ◽

pp. 3902

Author(s):

Kamil Konopka ◽

Agnieszka Micek ◽

Sebastian Ochenduszko ◽

Joanna Streb ◽

Paweł Potocki ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Advanced Gastric Cancer ◽

Cancer Patients ◽

Inflammatory Markers ◽

Cox Regression ◽

Risk Of Death ◽

Immune System Activation ◽

Increased Risk ◽

Gastric Cancer Patients

Background: Chemotherapy is a cornerstone of treatment in advanced gastric cancer (GC) with a proven impact on overall survival, however, reliable predictive markers are missing. The role of various inflammatory markers has been tested in gastric cancer patients, but there is still no general consensus on their true clinical applicability. High neutrophil-to-lymphocyte (NLR) and low (medium)-platelets-volume-to-platelet ratio (PVPR) are known markers of unspecific immune system activation, correlating significantly with outcomes in advanced GC patients. Methods: Metastatic GC patients (N:155) treated with chemotherapy +/− trastuzumab were enrolled in this retrospective study. Pre-treatment NLR and PVPR, as well as other inflammatory markers were measured in peripheral blood. Univariate Cox regression was conducted to find markers with a significant impact on overall survival (OS) and progression-free survival (PFS). Spearman correlation and Cohen’s kappa was used to analyze multicollinearity. Multiple multivariable Cox regression models were built to study the combined impact of NLR and PVPR, as well as other known prognostic factors on OS. Results: Elevated NLR was significantly associated with increased risk of death (HR = 1.95; 95% CI: 1.17–3.24), and lower PVPR was significantly associated with improved outcomes (HR = 0.53; 95% CI: 0.32–0.90). A novel inflammatory marker, based on a combination of NLR and PVPR, allows for the classification of GC patients into three prognostic groups, characterized by median OS of 8.4 months (95% CI 5.8–11.1), 10.5 months (95% CI 8.8–12.1), and 15.9 months (95% CI 13.5–18.3). Conclusion: The NLR and PVPR score (elevated NLR and decreased PVPR) is a marker of detrimental outcome of advanced GC patients treated with chemotherapy.

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