P-OGC06 The effect of surgical complications on long-term prognosis following oesophagectomy for oesophageal cancer

Abstract Background Globally, oesophageal cancer incidence continues to increase. In recent years, surgical and oncological advancements have increased survival rates. Despite this, survival remains <50% at five-years for patients treated with curative oesophagectomy. Previous data has suggested post-operative complications may play a role in long-term increased mortality in oesophageal cancer patients. This study aimed to examine the effect of adverse in-hospital events following oesophagectomy on the long-term prognosis for oesophageal cancer, including assessing the effect of cumulative complication burden using data from a single high-volume academic unit in the UK. Methods Retrospective analysis of patients undergoing oesophagectomy for oesophageal adenocarcinoma or squamous cell carcinoma was performed to assess the relationship between in-hospital events and long-term survival. Analysis was limited to patients who survived to 90 days post-oesophagectomy (n = 380). Complications were graded according to the Clavien-Dindo (CD) classification and the Comprehensive Complication Index (CCI). Survival was estimated using Kaplan Meier survival curves and multivariate cox-regression, adjusting for variables known to influence survival. The absolute magnitude of effect of complications on survival was assessed using the risk-adjusted population attributable fraction (PAF), which estimates the percentage improvement in survival if specified complications were removed. Results Complications occurred in 251 patients (66.1%). ≥CD3a complications (HR1.65, 95%CI 1.15-2.38, p < 0.010) and unplanned critical care admissions (HR2.24, 95%CI 1.45-3.46, p < 0.001) were independently associated with worse prognosis whereas pulmonary complications and anastomotic leak were not. A CCI >30 was the optimum cut-point for OS (HR1.94, 95%CI 1.36-2.78, p < 0.001), and after weighting to remove confounding bias median survival was shorter with CCI>30 (28vs72 months, p < 0.001). There was no difference in median survival when CCI>30 occurred from major or multiple minor complications (31 vs 21 months, p = 0.096). The risk adjusted PAF for CCI>30 was 8.5% (95%CI 3.6-13.1%). Conclusions Long-term survival following oesophagectomy for oesophageal cancer is significantly affected by major complications and unplanned critical care admissions. The cumulative effect of multiple post-operative minor complications is comparable to the effect of major complications on long-term survival from oesophageal cancer, and cause a substantial number of potentially preventable deaths, even in patients who survive to discharge.

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EXTH-13. LOCAL DELIVERY OF AN IL-15 SUPERAGONIST USING A REPLICATING RETROVIRUS SIGNIFICANTLY IMPROVES SURVIVAL AND LYMPHOCYTE INFILTRATION IN POORLY IMMUNOGENIC MURINE GLIOBLASTOMA MODELS

Neuro-Oncology ◽

10.1093/neuonc/noab196.652 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi166-vi166

Author(s):

Alexander Haddad ◽

Jordan Spatz ◽

Megan Montoya ◽

Sara Collins ◽

Sabraj Gill ◽

...

Keyword(s):

T Cell ◽

Median Survival ◽

T Cell Activation ◽

Term Survival ◽

Long Term Survival ◽

Immunosuppressive Cell ◽

Imaging Results ◽

Local Immunosuppression ◽

Inflammatory Changes

Abstract Glioblastoma (GBM) leads to severe systemic and local immunosuppression, and immunotherapies have had limited clinical success. Here, we evaluated the treatment efficacy of RLI, a superagonist of T-cell activator IL-15, delivered to tumor cells using a tumor-selective retroviral replicating vector (RRV) in the syngeneic murine SB28 and Tu2449 GBM models, which are both engineered to be poorly immunogenic with low-mutational burden and known resistance to immunotherapy, and hence more accurate biomimetic models of human GBM. RRV-RLI replicated and spread effectively in cultured murine GBM cells with robust production of functional RLI (165.4 ± 5.3 ng/mL). Stereotactic injection of RRV-RLI into pre-established intracerebral SB28 tumors significantly reduced tumor growth on bioluminescent imaging, and increased median survival compared to control mice (55 vs. 19 days, p=0.002), leading to long-term survival in 12% of treated mice. In the Tu2449 model, imaging results showed complete eradication of intracerebral tumors after RRV-RLI treatment, with long-term survival (median not reached) in > 85% of treated mice, compared to a median survival of 12.5 days in control mice (p=0.001). RRV-RLI treated tumors showed significantly increased CD8 T-cell infiltration, without altering immunosuppressive cell populations. Similarly, broad anti-tumor inflammatory changes, including increased expression of genes involved in T-cell activation and killing, were observed in the NanoString nCounter platform using a 770-gene panel representing various immune cell types. Notably, RLI was not detected in the blood of treated mice, and tumor-localized RRV-RLI gene delivery showed no adverse systemic immune effects in either model. In summary, RRV-mediated RLI immunotherapy results in immunostimulatory and pro-inflammatory changes to the tumor microenvironment and achieves a significant survival benefit in two poorly immunogenic syngeneic murine models of GBM. This tumor-localized immunomodulatory gene therapy has the potential to safely reverse the T-cell depleted immunophenotype of GBM.

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Long-term survival improvement in oesophageal cancer in the Netherlands

European Journal of Cancer ◽

10.1016/j.ejca.2018.02.025 ◽

2018 ◽

Vol 94 ◽

pp. 138-147 ◽

Cited By ~ 17

Author(s):

M. van Putten ◽

J. de Vos-Geelen ◽

G.A.P. Nieuwenhuijzen ◽

P.D. Siersema ◽

V.E.P.P. Lemmens ◽

...

Keyword(s):

The Netherlands ◽

Oesophageal Cancer ◽

Term Survival ◽

Long Term Survival

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64 STATISTICAL ANALYSIS OF PROGNOSTIC FACTORS AFFECTING LONG-TERM PROGNOSIS AFTER ENDOSCOPIC TREATMENT OF ESOPHAGEAL VARICES

Diseases of the Esophagus ◽

10.1093/dote/doaa087.10 ◽

2020 ◽

Vol 33 (Supplement_1) ◽

Author(s):

T Nishimura

Keyword(s):

Prognostic Factors ◽

Esophageal Varices ◽

Endoscopic Treatment ◽

Survival Period ◽

Term Survival ◽

Gastroesophageal Varices ◽

Long Term Survival ◽

Factors Affecting ◽

Long Term Prognosis

Abstract Gastroesophageal varices are present in approximately 50% of patients with cirrhosis, and their rupture is a life-threatening complication. However, mortality rates have declined due to the progress in the management of these patients. Especially advances in endoscopic treatment have contributed to the improved survival rates. In this study, we investigated the prognostic factors associated with long-term survival after endoscopic treatment for esophageal varices. Methods The subjects were 260 patients who underwent initial endoscopic treatment for esophageal varices in our hospital between January 1997 and June 2019. Among them, 160 successfully followed up. The patients’ characteristics were: mean age, 65.4 years (29–85); 109 men and 51 women; and median survival period, 53 months. For analysis, subjects were divided into long-term survival and non-long-term survival groups (n = 59 for each) with a 53-month survival period as a cut-off value. Results The long-term/non-long-term survival group had a preoperative Child-Pugh score of 6.2 ± 1.1/7.4 ± 2.0 (p < 0.01) and hepatocellular carcinoma (HCC) presence rate was 25.4%/55.9% (p < 0.01), significantly higher in the non-long-term group. Analysis of the factors affecting survival period using Cox proportional hazards model showed that Child-Pugh score B or C [hazard ratio(HR):2.0143, p < 0.05], total bilirubin value≧ 2 [HR:2.5573, p < 0.05], and presence of HCC [HR:2.2450, p < 0.01] were noted as significant factors. Only presence of HCC was found to be a significant factor affecting the long-term survival using multiple logistic regression analysis [odds ratio:0.3463, p < 0.05]. Conclusion Our study revealed that liver function and the presence of HCC affect long-term prognosis after endoscopic treatment for esophageal varices.

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Peritoneal Colorectal Carcinomatosis Treated With Surgery and Perioperative Intraperitoneal Chemotherapy: Retrospective Analysis of 523 Patients From a Multicentric French Study

Journal of Clinical Oncology ◽

10.1200/jco.2009.23.9285 ◽

2010 ◽

Vol 28 (1) ◽

pp. 63-68 ◽

Cited By ~ 582

Author(s):

Dominique Elias ◽

François Gilly ◽

Florent Boutitie ◽

François Quenet ◽

Jean-Marc Bereder ◽

...

Keyword(s):

Colorectal Cancer ◽

Median Survival ◽

Intraperitoneal Chemotherapy ◽

Combined Treatment ◽

Prognostic Impact ◽

Term Survival ◽

Multicentric Study ◽

Long Term Survival ◽

French Speaking

Purpose Peritoneal carcinomatosis (PC) from colorectal cancer traditionally is considered a terminal condition. Approaches that combine cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with that strategy. Patients and Methods A retrospective-cohort, multicentric study from French-speaking countries was performed. All consecutive patients with PC from colorectal cancer who were treated with CRS and PIC (with or without hyperthermia) were included. Patients with PC of appendiceal origin were excluded. Results The study included 523 patients from 23 centers in four French-speaking countries who underwent operation between 1990 and 2007. The median follow-up was 45 months. Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, and five-year disease-free survival was 10%. Complete CRS was performed in 84% of the patients, and median survival was 33 months. Positive independent prognostic factors identified in the multivariate analysis were complete CRS, PC that was limited in extent, no invaded lymph nodes, and the use of adjuvant chemotherapy. Neither the grade of disease nor the presence of liver metastases had a significant prognostic impact. Conclusion This combined treatment approach against PC achieved low postoperative morbidity and mortality, and it provided good long-term survival in patients with peritoneal scores lower than 20. These results should improve in the future, because the different teams involved will gain experience. This approach, when feasible, is now considered the gold standard in the French guidelines.

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Relapse Rate and Long-Term Survival of AL Amyloidosis Patients Treated with High-Dose Melphalan and Autologous Stem Cell Transplantation (HDM/SCT).

Blood ◽

10.1182/blood.v108.11.3094.3094 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3094-3094

Author(s):

David C. Seldin ◽

Martha Skinner ◽

Betul Oran ◽

Karen Quillen ◽

Kathleen T. Finn ◽

...

Keyword(s):

Median Survival ◽

Plasma Cell ◽

Relapse Rate ◽

Long Term Results ◽

High Dose ◽

Al Amyloidosis ◽

Term Survival ◽

Long Term Survival ◽

Early Results

Abstract AL amyloidosis is a plasma cell dyscrasia in which clonal immunoglobulin light chains misfold and are deposited in tissues, leading to organ failure in untreated patients, with median survival of only ~1 year. Oral melphalan and prednisone is minimally effective for the disease, with an increase in median survival to ~1.5 years, and a low rate of hematologic complete responses (CRs). Twelve years ago, we began treating patients with AL amyloidosis with HDM/SCT. In the plasma cell malignancy multiple myeloma, this approach produces hematologic CRs and improves survival, but is not curative, as all patients eventually relapse. In AL amyloidosis, the relapse rate and long-term survival have not been studied, but early results are promising, with most centers reporting CR rates of ~40% and excellent survival in responding patients. To address the durability and long-term results of treatment with HDM/SCT, here we report on the outcome for AL amyloidosis patients treated at Boston Medical Center with HDM/SCT >10 years ago. The first autologous transplant took place on July 18, 1994 in two years, by July 18, 1996, 43 patients with AL amyloidosis without myeloma or other hematologic disease had been treated with HDM/SCT, receiving 100–200 mg/m2 melphalan depending upon age and protocol. Of the 43 patients treated in this 2 yr period, 76% of the patients were male, 81% had a lambda monoclonal disease, and their median age was 52 (range, 29–71). In these first 43 patients, the 100 day peri-transplant mortality rate was 16%. Nineteen of the 43 patients (44%) achieved a hematologic CR after treatment. In annual followup, 4 of 19 patients (21%) eventually relapsed. Fourteen of 43 patients (33%) are still alive; 12 of 19 patients who achieved a CR (63%) are still alive, while only 2 of 34 patients who did not (6%) are still alive. Although there were fewer (8) patients with kappa clonal disease, they had a better outcome, with an 87% CR rate vs. 34% for lambda (P=0.006); 75% of the kappa patients are still alive, vs. 23% of the lambda patients (P=0.005). The median survival of all 43 patients is 4.7 years. Thus, treatment of AL amyloidosis patients with HDM/SCT produces a high CR rate that is durable and is associated with excellent 10 year survival, particularly for those patients achieving a hematologic CR and for patients with kappa clonal disease. Ongoing clinical trials of HDM/SCT, along with strategies to reduce morbidity and mortality and to improve the CR rate, incorporating additional cycles of HDM/SCT or new anti-plasma cell agents, appear to be well-justified by these results.

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Long-term survival in patients with peritoneal metastasized gastric cancer treated with cytoreductive surgery and HIPEC: A multi-institutional cohort from PSOGI.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.390 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 390-390

Author(s):

Andreas Brandl ◽

Yutaka Yonemura ◽

Olivier Glehen ◽

Paul H. Sugarbaker ◽

Beate Rau

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Median Survival ◽

Cytoreductive Surgery ◽

Peritoneal Metastasis ◽

Tumor Recurrence ◽

Term Survival ◽

Long Term Survival ◽

Crs And Hipec

390 Background: Peritoneal metastasis of gastric cancer is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in median survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyze a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics. Methods: We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven peritoneal metastasis of gastric cancer, treated with CRS and HIPEC, and overall survival > 5 years. Patient, tumor, and therapeutic details were collected and analyzed. Results: A total of 29 patients with a mean age of 52.5 years and a mean PCI of 3.2 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and low PCI (PCI < 6) were present in 23/29 patients. 13/29 patients developed at a median of 82.2 months tumor recurrence. Tumor recurrence was associated with inferior median overall survival compared to patients without tumor recurrence (8.8 years vs. not reached; p = 0.002). Conclusions: Long-term survival and even cure are possible in patients with peritoneal metastasis of gastric cancer treated with CRS and HIPEC. Completeness of cytoreduction (CC-0) and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.

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Effect of volatile and intravenous anesthesia on long-term survival of cancer surgery patients: a systematic review and meta-analysis

10.21203/rs.2.116/v2 ◽

2020 ◽

Author(s):

Li Gong ◽

Chao Dong ◽

Qian Cai ◽

Wen Ouyang

Keyword(s):

Cancer Patients ◽

Meta Analysis ◽

Cancer Surgery ◽

Anesthetic Techniques ◽

Breast Cancer Patients ◽

Term Survival ◽

Long Term Survival ◽

Long Term Prognosis ◽

The Impact

Abstract Background The impact of volatile anesthesia (INHA) and total intravenous anaesthesia (TIVA) on the long-term survival of patients after oncology surgery is a subject of controversy. The purpose of this study was to make overall evaluation of the association between these two anesthetic techniques and long-term prognosis of oncology patients after surgery. Methods Databases were searched according to the PRISMA guidelines up to September 30, 2018. Hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated after multivariable analyses and propensity score (PS) adjustments. Eight retrospective cohort articles reporting data on overall survival (OS) and recurrence-free survival (RFS) were included. An inverse variance random effects meta-analysis was conducted. The Newcastle Scale was used to assess methodological quality and bias. Results In total, about 18922 cancer patients observed were included in the meta-analysis, of which 10433 cases were available for analysis in INHA and 8489 in TIVA group. Compared to TIVA, INHA showed a shorter OS (HR =1.27, 95% CI 1.069 to 1.516, p=0.007), with a medium heterogeneity (Q-test p=0.003, I-squared=67.6%). However, no significant differences were identified between INHA and TIVA group (HR =1.10, 95% CI 0.729 to 1.659, p=0.651) concerning RFS albeit from a limited data pool. When a subgroup analysis was performed by race, the association was more likely to be observed in the Asian studies (HR=1.46, 95%CI 1.19–1.8, p =0.00), with a much lower heterogeneity (Q-test p=0.148, I-squared=44%). When comparison was done only in breast cancer patients, no significant differences were found for OS (HR=1.625, 95%CI 0.273-9.67, p=0.594) between INHA and TIVA. Conclusion TIVA for cancer surgery might be associated with better OS compared to INHA. The effect of INHA and TIVA on OS and RFS in the perioperative setting remains uncertain, cancer-specific, and has low-level evidence at present. Randomized controlled trials are required in future work. Registry number The review protocol was registered with PROSPERO (Registration NO.CRD42018109341).

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Characterisation of long-term cancer survivors and application of statistical cure models: a protocol for an observational follow-up study in patients with colorectal cancer

BMC Public Health ◽

10.1186/s12889-020-09807-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Sonia Pértega-Díaz ◽

Vanesa Balboa-Barreiro ◽

Rocío Seijo-Bestilleiro ◽

Cristina González-Martín ◽

Remedios Pardeiro-Pértega ◽

...

Keyword(s):

Colorectal Cancer ◽

Term Survival ◽

Long Term Survival ◽

Follow Up Study ◽

Cure Models ◽

Long Term Prognosis ◽

Clinical Records ◽

Long Term Survivors

Abstract Background Improved colorectal cancer (CRC) survival rates have been reported over the last years, with more than half of these patients surviving more than 5 years after the initial diagnosis. Better understanding these so-called long-term survivors could be very useful to further improve their prognosis as well as to detect other problems that may cause a significant deterioration in their health-related quality of life (HRQoL). Cure models provide novel statistical tools to better estimate the long-term survival rate for cancer and to identify characteristics that are differentially associated with a short or long-term prognosis. The aim of this study will be to investigate the long-term prognosis of CRC patients, characterise long-term CRC survivors and their HRQoL, and demonstrate the utility of statistical cure models to analyse survival and other associated factors in these patients. Methods This is a single-centre, ambispective, observational follow-up study in a cohort of n = 1945 patients with CRC diagnosed between 2006 and 2013. A HRQoL sub-study will be performed in the survivors of a subset of n = 485 CRC patients for which baseline HRQoL data from the time of their diagnosis is already available. Information obtained from interviews and the clinical records for each patient in the cohort is already available in a computerised database from previous studies. This data includes sociodemographic characteristics, family history of cancer, comorbidities, perceived symptoms, tumour characteristics at diagnosis, type of treatment, and diagnosis and treatment delay intervals. For the follow-up, information regarding local recurrences, development of metastases, new tumours, and mortality will be updated using hospital records. The HRQoL for long-term survivors will be assessed with the EORTC QLQ-C30 and QLQ-CR29 questionnaires. An analysis of global and specific survival (competitive risk models) will be performed. Relative survival will be estimated and mixture cure models will be applied. Finally, HRQoL will be analysed through multivariate regression models. Discussion We expect the results from this study to help us to more accurately determine the long-term survival of CRC, identify the needs and clinical situation of long-term CRC survivors, and could be used to propose new models of care for the follow-up of CRC patients.

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Efficacy of Neoadjuvant Therapy in Improving Long-Term Survival of Patients with Resectable Rectal Cancer: A Meta-Analysis

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210726134809 ◽

2021 ◽

Vol 21 ◽

Author(s):

Xinlong Li ◽

Xiangyuan Li ◽

Rongrong Fu ◽

Derry Ng ◽

Tong Yang ◽

...

Keyword(s):

Rectal Cancer ◽

Neoadjuvant Therapy ◽

Meta Analysis ◽

Low Rectal Cancer ◽

Cochrane Library ◽

Term Survival ◽

Long Term Survival ◽

Resectable Rectal Cancer ◽

Long Term Prognosis

Background: The impact of neoadjuvant therapy on long-term prognosis of patients with resectable rectal cancer is currently unknown. Objective: This study aimed to explore the long-term prognosis of patients with resectable rectal cancer following treatment with neoadjuvant therapy. Methods: Four major databases (PubMed, Web of Science, Embase, Cochrane library) were searched to identify relevant articles published between January 2000 and July 2020. The main outcome indicators were the 5-year overall survival (OS) and disease-free survival (DFS). Results: The meta-analysis revealed that 5-year OS (HR: 0.88, 95% Cl: 0.83-0.93) and DFS (HR: 0.95, 95% Cl: 0.91-0.98) were higher in patients with resectable rectal cancer after receiving neoadjuvant therapy than those treated with upfront surgery. Subgroup analysis demonstrated that the long-term survival of patients in Asia and Europe could benefit from neoadjuvant therapy. The neoadjuvant short-course radiotherapy (SCRT) and neoadjuvant chemo-radiotherapy (CRT) improved the 5-year OS and DFS of patients with stage Ⅱ-Ⅲ rectal cancer and mid/low rectal cancer. Further research found that patients with stage Ⅱ only had an increase in OS, while patients with stage Ⅲ have improved 5-year OS and DFS. Conclusion: Neoadjuvant therapy improved the long-term survival of patients with mid/low rectal cancer in stage Ⅱ-Ⅲ (especially stage Ⅲ). Additionally, patients in Asia and Europe seemed to be more likely to benefit from neoadjuvant therapy. For the treatment, we recommend neoadjuvant SCRT and neoadjuvant CRT for resectable rectal cancer.

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