Prediction of survival in patients with colorectal liver metastases- development and validation of a prognostic score model

BackgroundMetastatic spread of colorectal cancer to the liver impacts prognosis. Advances in chemotherapy have resulted in increased resectability rates and thereby improved survival in patients with colorectal liver metastases (CRLM). However, criteria are needed to ensure that patients selected for hepatic resection benefit from the invasive therapy. The study aimed to construct a predictive model for overall survival (OS) in patients with CRLM, based on preoperatively available information.MethodsThe retrospective cohort study reviewed all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, Stockholm, Sweden, 2013–2018. Independent prognostic factors for OS were identified, based on which a score model was generated. The model was validated on patients treated for CRLM at Hôpital Universitaire Paul Brousse, Villejuif, France, 2007–2018. Calibration and discrimination methods were used for internal and external validation.ResultsThe Swedish development cohort included 1013 patients, the French validation cohort 391 patients. Poor OS was significantly associated with age>60years (hazard ratio (HR) 3.57 (95%CI 2.18–9.94)), number of CRLM (HR 4.59 (2.83–12.20)), diameter of largest CRLM>5 cm (HR 2.59 (1.74–5.03)), right-sided primary tumour (HR 2.98 (2.00–5.80)), extrahepatic disease (HR 4.14 (2.38–15.87)) and non-resectability (HR 0.77 (0.66-0.90)). The C-statistic for prediction of OS was .74, in the development cohort and 0.69 in the validation cohort.ConclusionThe presented predictive score model can adequately predict OS for patients at the initial diagnosis of CRLM. The prognostic model could be of clinical value in the management of all patients with CRLM, by predicting individualized survival and thereby facilitating treatment recommendations.     

A PET-based nomogram for oropharyngeal cancers

PurposeIn the context of locally advanced oropharyngeal cancer (LAOC) treated with definitive radiotherapy (RT) (combined with chemotherapy or cetuximab), the aims of this study were: (1) to identify PET-FDG parameters correlated with overall survival (OS) from a first cohort of patients; then (2) to compute a prognostic score; and (3) finally to validate this scoring system in a second independent cohort of patients.Materials and methodsA total of 76 consecutive patients (training cohort from Rennes) treated with chemoradiotherapy or RT with cetuximab for LAOC were used to build a predictive model of locoregional control (LRC) and OS based on PET-FDG parameters. After internal calibration and validation of this model, a nomogram and a scoring system were developed and tested in a validation cohort of 46 consecutive patients treated with definitive RT for LAOC in Lausanne.ResultsIn multivariate analysis, the metabolic tumour volume (MTV) of the primary tumour and the lymph nodes were independent predictive factors for LRC and OS. Internal calibration showed a very good adjustment between the predicted OS and the observed OS at 24 months. Using the predictive score, two risk groups were identified (median OS 42 versus 14 months, p < 0.001) and confirmed in the validation cohort from Lausanne (median OS not reached versus 26 months, p = 0.008).ConclusionsThis is the first report of a PET-based nomogram in oropharyngeal cancer. Interestingly, it appeared stronger than the classical prognostic factors and was validated in independent cohorts markedly diverging in many aspects, which suggest that the observed signal was robust.     

Prospective validation of a prognostic score for patients in immunotherapy phase I trials: The Gustave Roussy Immune Score (GRIm-Score)

IntroductionLife expectancy evaluation is crucial when selecting patients who may benefit from phase I studies. The Royal Marsden Hospital (RMH) prognostic score, based on three objective variables (number of metastatic sites, lactate dehydrogenase (LDH) and serum albumin) was validated in patients treated with cytotoxics and targeted therapies. We aimed to determine if those factors were applicable to immune-checkpoint therapies (ICTs) in phase I trials and to evaluate new variables that may preclude a better prognosis in patients receiving ICT.Patients and methodsWe conducted a retrospective analysis of survival risk factors in a discovery cohort of 155 patients enrolled into ICT phase I trials at our institution. We computed univariate analysis and multivariate analysis (MVA) of demographics, clinical and biological data to assess their prognostic value for overall survival (OS). MVA results were used to build a prognostic score for OS. A validation cohort of 113 patients enrolled in phase I ICT trials was used to prospectively validate this score.ResultsA total of 155 patients (M/F: 83/72; median age 59) receiving an experimental ICT between March 2012 and January 2016 were included in the discovery cohort. An MVA assessing the RMH score variables showed that low albumin (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.05–2.86) and LDH > upper limit normal (ULN) (HR 1.88, 95% CI 1.12–3.15) were independent negative prognostic factors for OS. Interestingly, neutrophil-to-lymphocyte ratio (NLR) > 6 (HR 1.75, 95% CI 1.04–2.95) was associated with a decrease in OS. The number of metastases was not associated with a poorer outcome for this ICT cohort (HR 0.83, 95% CI 0.51–1.35). A risk score based on the results of the MVA (NLR > 6 = 1; LDH > ULN = 1; albumin < 35 g/l = 1) showed that patients presenting a high score (>1) had a significantly shorter OS (20.4 weeks; 95% CI 5.7–35.2) compared to those with a low score (0 or 1) (68.9 weeks; 95% CI 50–83.7) (HR 2.9, 95% CI 1.87–4.64). In the validation cohort of 113 patients, again the patients presenting a high score showed an inferior OS (HR 6.3, 95% CI 2.7–14.8).ConclusionIn ICT phase I trials, traditional prognostic variables included in the RMH score may be suboptimal to determine patient's prognosis. In this context, the NLR is a significant prognostic variable. The Gustave Roussy Immune Score, based on albumin, LDH and NLR, allows a better selection of patients for ICT phase I trials.     

A novel pretherapeutic gene expression-based risk score for treatment guidance in gastric cancer

BackgroundPerioperative chemotherapy is an established treatment of advanced gastric cancer patients. Treatment selection is based on clinical staging (cT). We aimed to establish and validate a prognostic score including clinical and molecular factors, to optimize treatment decisions for these patients.Patients and methodsWe analyzed 626 carcinomas of the stomach and of the gastro-esophageal junction from two academic centers including primarily resected and pre-/perioperatively treated patients. Patients were divided into a training (N = 269) and validation (N = 357) set. Expression of 11 target genes was measured by quantitative PCR in resected tumors. A risk score to predict overall survival (OS) was generated and validated. Intra-tumoral heterogeneity was assessed by analyzing 50 tumor areas from 10 patients.ResultsA risk score including the expression of CCL5, CTNNB1, EXOSC3 and LZTR1 and the clinical parameters cT, tumor localization and histopathologic type suggested two groups with a significant difference in OS [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.17–0.52]. The risk score was successfully validated in an independent cohort (HR 0.32; 95% CI 0.21–0.51; P < 0.001) as well as in subgroups of primarily resected (HR 0.30; 95% CI 0.17–0.54; P < 0.001) and pre-/perioperatively treated patients (HR 0.37; 95% CI 0.17–0.81; P = 0.009). A significant difference in OS of high- and low-risk patients was also found in primarily resected patients with intestinal (HR 0.45; 95% CI 0.23–0.90; P = 0.020) and nonintestinal-type carcinomas (HR 0.1; 95% CI 0.02–0.42; P < 0.001). Intra-tumor heterogeneity analysis indicated a classification reliability of 95% for a supposed analysis of three biopsies.ConclusionThe identified risk score could substantially contribute to an improved management of gastric cancer patients in the context of perioperative chemotherapy.     

The prognostic role of the preoperative systemic immune-inflammation index and high-sensitivity modified Glasgow prognostic score in patients after radical operation for soft tissue sarcoma

IntroductionThe prognostic values of nutritional and immune-inflammatory indicators in non-metastatic soft tissue sarcoma (STS) patients are not clear. We investigated the utility of systemic immune-inflammation index (SII) and the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) in the prediction of STS patient's prognosis.Materials and methodsPatients admitted between January 2000 and December 2016, who underwent R0 resection for STS at SYSUCC were carefully retrospectively reviewed, and 454 patients were enrolled. The laboratory data and clinical data were collected from the patient's record. ROC analysis is used to determine the optimal cutoff value. Survival curves were analysed by Kaplan-Meier method. Cox proportional hazard model was used to find out prognostic variables.ResultsIncreased SII and Hs-mGPS values were significantly related to larger tumour size, deep tumour location, higher tumour grade and more advanced American Joint Committee on Cancer (AJCC) stage. Patients with an elevated SII had a shorter median survival time and a lower 5-year OS rate than those with a low SII. And patients with low Hs-mGPS had longer median OS and DFS. Multivariate analysis revealed that both the SII and the Hs-mGPS were independent predictive indicators for OS. And a joint model containing both the Hsm-GPS and the SII appeared to have the strongest predictive ability.ConclusionOur findings indicated that malnutrition and systemic inflammation are risk factors for the survival of STS patients after operation, and early recognition and intervention of malnutrition and systemic inflammation may help to improve the survival of the patients.     

Prognostic score for patients with advanced melanoma treated with ipilimumab

BackgroundImmunotherapies like the cytotoxic T-lymphocyte antigen 4 inhibitor ipilimumab show durable clinical benefit in patients with advanced melanoma. Reliable prognostic markers and risk scores in the era of immunotherapy are still lacking.Patients and methodsWe collected characteristics and outcomes on 134 patients with metastatic melanoma treated with ipilimumab between 2011 and 2014 at a single centre. Cox regression including multivariable fractional polynomials was used to identify independent markers for overall survival (OS). Internal model validation was done using bootstrap procedures.ResultsAfter a median follow-up of 16.1 months the median OS was 7.1 months (95% confidence interval [CI], 6.5–9.8). Nineteen of 134 patients (14.2%) had tumour remissions, 16 partial and 3 complete; 75% had progressive disease. We identified three independent adverse factors for OS: elevated lactate dehydrogenase (LDH) (hazard ratio [HR] 1.03, 95% CI 1.02–1.04), Eastern Cooperative Oncology Group performance status >0 (HR 1.91, 95% CI 1.10–3.30), and number of organs involved (NOI) (HR 1.51, 95% CI 1.22–1.86). To build an easy-to-apply risk score, we dichotomized LDH (>upper limit of normal) and NOI (>2) to built 3 prognostic groups: favourable (no adverse factors, N = 17), intermediate (1 adverse factor, N = 38), and poor prognosis (≥2 adverse factors, N = 73). Respective 12 and 18-month OS for the risk groups were: 85% and 73% (favourable), 41% and 29% (intermediate), and 12% and 6% (poor) (p < 0.001).ConclusionWe propose a simple prognostic score for survival in patients with advanced melanoma treated with ipilimumab using readily available clinical parameters.     

Risk factors in germ cell tumour patients with relapse or progressive disease after first-line chemotherapy: evaluation of a prognostic score for survival after high-dose chemotherapy

PurposeTo retrospectively re-evaluate a published prognostic score for response to salvage treatment in patients with germ-cell tumours relapsing or progressing after cisplatin-based first-line chemotherapy.Patients and methodsFrom a database of 257 germ cell tumour (GCT) patients treated with salvage high-dose chemotherapy (HDCT) we identified 176 patients (67%) with relapse or progression after first-line conventional-dose chemotherapy (CDCT). Patients were retrospectively grouped according to a published prognostic score defined by Fossa and colleagues [Fossa SD, Stenning SP, Gerl A, et al. Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumors. Br J Cancer 1999; 80:1392–9]. Overall survival (OS) and event free survival (EFS) after HDCT were retrospectively evaluated in each prognostic group.ResultsAfter a median follow-up of 9 years the OS probability for all 176 patients was 38% and the EFS probability was 35%. The respective survival probability at 5 years in 100/176 (57%) good prognosis patients and 76/176 (43%) poor prognosis patients were 47% versus 28% for OS (p < 0.001) and 41% versus 26% for EFS (p < 0.005). Whereas survival probabilities did not differ in good prognosis patients, OS and EFS in poor prognosis patients were substantially better in the current series of patients treated with HDCT compared to the ones reported by Fossa treated with CDCT.ConclusionThis retrospective analysis confirms the impact of prognostic factors on the results of salvage treatment in patients with GCT and suggests a clinical benefit for patients with poor prognosis features receiving a single course of HDCT.     

Initial biopsy and early re-resection practices in the treatment of glioblastoma among AANS/CNS tumor section surgeons

Purpose

The aim of this study is to investigate the association between postoperative tumor volume and overall survival (OS) of O⁶-methylguanine DNA methyltransferase (MGMT)-unmethylated glioblastoma patients.

Methods

One hundred-twenty-six patients with MGMT-unmethylated glioblastoma who were treated either with surgical resection or needle biopsy between 2006 and 2015 were included in this retrospective cohort. Pre- and postcontrast T1 weighted images were evaluated in order to determine pre- and postoperative contrast-enhancing tumor volumes (CE-TV). Cox regression models adjusted for other significant prognostic factors were used to investigate the association between postoperative tumor volume and survival.

Results

Complete resection of CE-TV was significantly associated with longer OS in the univariate analysis (HR 0.61; 95% CI 0.40–0.94; p?=?0.02). However, this fact could not be confirmed after adjusting the model for other relevant prognostic factors (HR 1.01; 95% CI 0.65–1.55; p?=?0.962). Postoperative CE-TV was significantly associated with survival in both univariate (HR: 1.04; 95% CI 1.025–1.055; p?<?0.001) and multivariate analyses (HR: 1.027; 95% CI 1.005–1.049; p?=?0.014).

Conclusions

Although complete resection of tumor tissue was not significantly associated with longer OS in MGMT-unmethylated GBM patients, maximum safe resection should always be attempted, since postoperative tumor volume is strongly associated with OS.

     

Impact of timing and cycles of systemic chemotherapy on survival outcome of colorectal liver metastases patients treated by percutaneous microwave ablation

Purpose: The aim of this retrospective study is to determine the optimal timing and number of cycles of systemic chemotherapy in patients with colorectal liver metastases (CLM) treated by ultrasound-guided percutaneous microwave ablation (PMWA).

Materials and methods: In total 199 patients with 318 CLM, median number of tumours one per patient and median maximum size of tumours 3.0?cm, treated by PMWA combined with or without systemic chemotherapy were included in our study. Chemotherapy was administered pre-ablatively in 148 of those patients (74.4%), and post-ablatively in 142 (73.6%). Chemotherapy regimens included FOLFOX/XELOX, FOLFIRI/XELIRI, and sequential monotherapy. Prognostic factors were evaluated by univariate and multivariate analyses, using log-rank test and Cox proportional hazards model, respectively.

Results: The estimated 5-year rates of progression free survival (PFS) and overall survival (OS) were 10.1% and 27.9%, respectively. The number of CLM (P?=?0.003), maximum size of CLM (P?<?0.001) and topography (P?=?0.030) were independent prognostic factors for PFS of patients with CLM while age (P?=?0.002), maximum size of CLM (P?=?0.006) and post-ablative chemotherapy (P?=?0.046) for OS. In further analysis, CLM patients receiving more than six cycles of post-ablative chemotherapy had significantly better OS (P?=?0.015) than those without post-ablative chemotherapy.

Conclusion: This study revealed chemotherapy administered after (more than six cycles) PMWA improved the OS of CLM patents. And, PMWA was a safe procedure in view of the absence of procedure-related death and low rate of major complications.     

Clinical assessment of patients with advanced non-small-cell lung cancer eligible for second-line chemotherapy: A prognostic score from individual data of nine randomised trials

PurposeKnowledge of prognostic factors for advanced non-small-cell lung cancer (NSCLC) patients eligible for second-line treatment is scarce. The aim of this study was to assess the prognostic role of a number of routinely collected clinical variables and to provide a summary index to discriminate patients according to probability of survival.MethodsIndividual data from nine randomised trials of second-line treatment in advanced NSCLC were analysed. Primary end-point was overall survival (OS). Cox model, stratified by trial, was used for multivariate analyses, and a prognostic index was provided and validated according to an internal/external procedure.ResultsOut of 1239 patients, 1197 patients (97%) had complete information. Median OS was 7.4 months. At multivariate analysis, prognosis was significantly influenced by gender (worse in males), performance status (PS), tumour histology (worse in squamous and other histology versus adenocarcinoma), stage (worse in IV versus IIIB), type of previous treatment (worse for patients pretreated with platinum) and response to first-line (worse for patients not obtaining objective response). Prognostic score values range from 0 to 14. When three categories were derived, median overall survival values were equal to 11.6, 7.5 and 3.0 months for best (<5), intermediate (5-9) and worst (>9) categories, respectively.ConclusionPrognosis of patients eligible for second-line treatment of advanced NSCLC is significantly conditioned by gender, PS, histology, stage, previous use of platinum and response to first-line. A prognostic score was derived that discriminates well subjects with a relatively more favourable prognosis and those with very short life expectancy.     

Tertiary lymphoid structure score: a promising approach to refine the TNM staging in resected non-small cell lung cancer

Background We previously proposed an immune cell score (tumour node metastasis (TNM)-Immune cell score) classifier as an add-on to the existing TNM staging system for non-small cell lung cancer (NSCLC). Herein, we examined how to reliably assess a tertiary lymphoid structure (TLS) score to refine the TNM staging system.Methods Using immunohistochemistry (CD8/cytokeratin), we quantified TLS in resected NSCLC whole-tumour tissue sections with three different scoring models on two independent collections (total of 553 patients). In a pilot setting, NanoString gene expression signatures were analysed for associations with TLS.Results The number of TLSs significantly decreased in stage III patients as compared to stage II. The TLS score was an independent positive prognostic factor, regardless of the type of (semi)-quantification strategy used (four-scale semi-quantitative; absolute count of total TLS; subpopulation of mature TLS) or the endpoint (disease-specific survival; overall survival; time to recurrence). Subgroup analyses revealed a significant prognostic impact of TLS score within each pathological stage, patient cohort and main histological subtype. Targeted gene expression analysis showed that high TLS levels were associated with the expression of B cell and adaptive immunity genes/metagenes including tumour inflammation signature.Conclusions The TLS score increases the prognostic power in each pathological stage and hence has the potential to refine TNM staging in resected NSCLC.Subject terms: Surgical oncology, Translational immunology, Prognostic markers     

Nomograms for survival prediction in patients undergoing liver resection for hepatitis B virus related early stage hepatocellular carcinoma

BackgroundThe long-term outcomes of patients who underwent liver resection (LR) for early-stage hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) are difficult to predict. This study aimed to develop two nomograms to predict postoperative disease-free survival (DFS) and overall survival (OS), respectively.MethodsData on a primary cohort of 1328 patients who underwent LR for HBV-related HCCs within Milan criteria at the Eastern Hepatobiliary Surgery Hospital (EHBH) from 2000 to 2006 were used to develop the nomograms by the Cox regression analyses. An internal validation cohort of 442 patients operated from 2006 to 2011 at the EHBH and an external validation cohort of 474 patients operated from 2007 to 2009 at the Zhongshan Hospital were used for validation studies. Discrimination and calibration were measured using concordance index (C-index), calibration plots and Kaplan–Meier curves.ResultsThe independent predictors of DFS or OS which included tumour stage factors, biomarker and HBV–DNA level were respectively incorporated into the two nomograms. In the primary cohort, the C-indexes of the models in predicting DFS and OS were 0.76 (95% confidence interval: 0.75–0.78) and 0.79 (0.77–0.81), respectively. The calibration curves fitted well. Both nomograms accurately stratify patients into four distinct incremental prognostic subgroups. The C-indexes of the nomogram for OS prediction was significantly higher than those of the six conventional staging systems (0.65–0.71, all P < 0.001). These results were verified by the internal and external validations.ConclusionThe proposed nomograms showed good prognostication for patients with early HBV-related HCCs after hepatectomy.     

Lung Immune Therapy Evaluation (LITE) Risk,a Novel Prognostic Model for Patients With Advanced Non-Small Cell Lung Cancer Treated With Immune Checkpoint Blockade

Introduction/BackgroundImmune checkpoint inhibitors (ICI) have revolutionized non-small cell lung cancer (NSCLC). We aimed to identify baseline characteristics, that are prognostic factors for overall survival (OS) in patients with NSCLC treated with ICI monotherapy, in order to derive the Lung Immune Therapy Evaluation (LITE) risk, a prognostic model.Materials and MethodsMulti-center observational cohort study of patients with advanced NSCLC that received ≥1 dose of ICI monotherapy. The training set (n=342) consisted of patients with NSCLC who received first line ICI. The test set (n=153) used for external validation was a discrete cohort of patients who received second line ICI. 20 candidate prognostic factors were examined. Penalized Cox regression was used for variable selection. Multiple imputation was used to address missingness.ResultsThree baseline characteristics populated the final model: ECOG (0, 1 or ≥2), lactate dehydrogenase>upper limit of normal, and derived neutrophil to lymphocyte ratio ≥3. Patients were parsed into 3 risk groups; favorable (n=146, risk score 0-1), intermediate (n=101, risk score 2) and poor (n=95, risk score ≥3). The c-statistic of the training cohort was 0.702 and 0.694 after bootstrapping. The test cohort c-statistic was 0.664.The median OS for favorable, intermediate and poor LITE risk were; 28.3 months, 9.1 months and 2.1 months respectively. Improving LITE risk group was associated with improved OS, intermediate vs favorable HR 2.08 (95%CI 1.46-2.97, P < .001); poor vs favorable HR 5.21 (95%CI 3.69-7.34, P < .001).ConclusionA simple prognostic model, utilizing accessible clinical data, can discriminate survival outcomes in patients with advanced NSCLC.     

Prediction of late recurrence after radiofrequency ablation of HBV-related hepatocellular carcinoma with the age-male-albumin-bilirubin-platelets (aMAP) risk score: a multicenter study

BackgroundLong-term survivals of patients with HBV-related hepatocellular carcinoma are limited by the high incidence of tumor recurrence after radiofrequency ablation (RFA), identification of the risk factors and understanding the patterns of recurrence can help to improve the comprehensive management of patients after RFA. Therefore, the purpose of the study is to explore the prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in patients with early-stage HBV-related hepatocellular carcinoma (HCC) receiving RFA; investigate the risk factors and patterns of late recurrence (LR); and develop a nomogram to predict recurrence-free survival (RFS).MethodsA retrospective review of HBV-related HCC patients who underwent primary RFA from March 2012 to December 2020 was conducted. The prognostic value of the aMAP score was evaluated in a primary cohort (n=302) and then further validated in an independent validation cohort (n=143). The optimal threshold of aMAP scores was calculated by X-tile 3.6.1 software. A prognostic nomogram was constructed from multivariate analysis and validated in an external validation cohort.ResultsPatients with aMAP scores ≤63.8, 63.8–67.8, and >67.8 were classified into low-, medium-, and high-recurrence risk groups, respectively. The C-index to predict LR was 0.76 (95% CI: 0.700–0.810). The high-risk group was associated with the worst RFS (HR: 5.298; 95% CI, 2.697–10.408; P<0.001) and overall survival (OS) (HR: 2.639; 95% CI, 1.097–6.344; P=0.03) compared with medium- and low-risk groups. The aMAP score, multiple tumors and preoperative HBV DNA level were independent risk factors for LR. The proposed nomogram had excellent performance in predicting LR of HBV-related HCC [C-index: 0.82 (95% CI: 0.772–0.870)].ConclusionsThis study demonstrated that the aMAP score can serve as an objective predictor of LR for HBV-related HCC patients after RFA. The nomogram based on preoperative HBV DNA level, aMAP score, and number of tumors can reliably help clinicians to stratify the recurrence risk of HCC patients after RFA.     

Improved survival in metastatic germ-cell cancer

BackgroundThe prognostic score of the International Germ-Cell Cancer Collaborative Group (IGCCCG) in metastatic germ-cell cancers (mGCC) relies on treatments delivered before 1990. It is unclear, if this score is still relevant to contemporary cohorts of patients who receive modern-type chemotherapy and supportive care.Patients and methodsAll patients who underwent cisplatin/etoposide-based first-line chemotherapy for mGCC at the University Hospital Zurich (USZ) between 1991 and 2016 were identified retrospectively. Clinical characteristics were extracted from medical charts and patients classified according to the IGCCCG score. International germ cell consensus classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 1997; 15: 594–603.). Progression-free survival (PFS) and overall survival (OS) probabilities at 5 years served as outcome parameters.ResultsThe study cohort consisted of 204 patients at a median age of 32 years and a median follow-up of 4.2 years. According to the IGCCCG score, PFS in the contemporary USZ cohort was 71% overall: 83% for good-risk, 69% for intermediate-risk and 30% for poor-risk patients, P < 0.001. OS for the entire cohort was 88%. In respect to OS, we observed no difference between good- and intermediate-risk patients (94% versus 91%, P = 0.62), but a statistically significant difference between those two risk groups and poor-risk patients, who had an OS of only 65%, P < 0.001.ConclusionsWithin the contemporary USZ cohort of mGCC patients no improvements in PFS probabilities were observed compared with the ones predicted by the IGCCCG score for any prognostic category, but marked improvements in OS probabilities for intermediate- and poor-risk patients, possibly due to better salvage treatments.     

Novel implications of combined arterial resection for locally advanced pancreatic cancer in the era of newer chemo-regimens

IntroductionIn this study, we assessed the prognostic efficacy and feasibility of combined arterial resection (AR) for locally advanced pancreatic cancer (LAPC), and aimed to identify significant prognostic factors for patients who underwent combined AR.MethodsBetween 1981 and 2018, 733 consecutive patients who underwent pancreatic surgery for PC were identified. The 730 cases with detailed information were enrolled in the analysis.ResultsAmong 730 resected PC patients, 44 (6%) underwent AR including 21 hepatic (48%), 12 celiac (27%), five splenic (12%), four superior mesenteric (9%), and two other arteries (4%). The combined AR surgery showed significantly longer operative time (median, 608 vs 451 min, P < 0.0001), and the incidence of intraoperative blood transfusion was significantly higher in AR than surgery without AR (P = 0.0002), whereas there was no significant difference in the intraoperative blood loss (970 vs 1200 mL, P = 0.2) and occurrence of major complications (P = 0.5). In prognostic analysis of AR cases, multivariate Cox proportional hazard models revealed preoperative and postoperative therapy were the independent factors for both recurrence-free survival (RFS) and overall survival (OS) (preoperative therapy: RFS, HR = 0.21, P = 0.007; OS, HR = 0.18, P = 0.01; postoperative therapy: RFS, HR = 0.31, P = 0.003; OS, HR = 0.19, P = 0.002).ConclusionThis study showed the feasibility of combined AR for LAPC and robust association of pre- and postoperative therapy and survival after AR surgery. Preoperative therapy following combined AR surgery is potentially powerful strategy for LAPC.     

The survival difference between gastric cancer patients from the UK and Japan remains after weighted propensity score analysis considering all background factors

Background

Previous studies comparing survival between gastric cancer (GC) patients from the West and the East were based on the assumption that background factors and prognostic factors were identical. The aim of the current study was to compare the survival of GC patients from the UK and Japan using weighted propensity score analysis after identifying all different background factors.

Methods

Data from 464 patients from the Leeds Teaching Hospital NHS Trust, Leeds, UK (LTHT), and 465 patients from the Kanagawa Cancer Center Hospital, Yokohama, Japan (KCCH), who had surgery for GC were analyzed. Prognostic factors for overall survival (OS) and cancer-specific survival (CSS) were identified by univariate and multivariate analyses. Survival was compared by propensity score weighting after adjusting for all significantly different background factors.

Results

Most background factors were different between LTHT and KCCH patients. Unadjusted stage-specific OS and CSS were significantly better in KCCH. Independent prognostic factors for unadjusted OS and CSS were pT and pN in KCCH and in addition tumor location, pancreatectomy, resection margin status and number of examined lymph nodes in LTHT. Even after adjusting for all background characteristics, survival remained better in KCCH.

Conclusions

These results suggest that differences in background factors are unable to fully explain the survival difference of GC patients between UK and Japan. Comprehensive studies into the biology of GC and/or host factors are needed to fully understand the survival difference.

     

Survival analysis and prognostic factors of palliative radiotherapy in patients with metastatic colorectal cancer: a propensity score analysis

BackgroundRadiation therapy (RT) is known to have beneficial effects on the palliative treatment of patients with advanced cancer. However, valid data on this treatment method are limited, especially for patients with metastatic colorectal cancer (mCRC). This study aimed to identify prognostic factors and investigate the outcomes of mCRC patients who received palliative RT.MethodsA total of 488 mCRC patients who underwent systemic therapy with or without palliative RT between 2014 and 2019 were included in the study. Of the 488 patients, 155 received systemic treatment combined with palliative RT (RT group), while 333 were only administered systemic treatment (non-RT group). Propensity score matching (PSM) was conducted to eliminate possible bias, and overall survival (OS) was calculated using the Kaplan-Meier (KM) method. A log-rank test was used to compare the survival outcomes of each group, and a multivariate analysis was conducted using a Cox proportional hazards model.ResultsThe RT group had a higher OS than that of the non-RT group (P=0.001). After PSM, the median OS of the RT group was 50.8 months, and for the non-RT group it was 32.2 months (P=0.003). Subgroup analysis revealed that RT had a better effect on the OS of patients who had synchronous metastasis, or who didn’t receive targeted therapy or local treatment (including surgery, ablation, and intervention). Multivariate analysis of the whole cohort showed that palliative RT was associated with improved OS. Moreover, multivariate analysis of the RT group showed that systemic therapy before RT, and the site of RT was in the liver and lung, were independent prognostic factors affecting survival time.ConclusionsWe demonstrated that systemic treatment followed by palliative RT led to a better OS for mCRC patients. This combination method can therefore be seen as a suitable treatment approach for patients with mCRC.     

Surgical Management of Metastatic Colorectal Cancer: A Single-Centre Experience on Oncological Outcomes of Pulmonary Resection vs Cytoreductive Surgery and HIPEC

Purpose

Metastasectomy is accepted as standard of care for selected patients with colorectal pulmonary metastases (CLM); however, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM) is not universally accepted. We aim to compare oncological outcomes of patients with CLM and CPM after pulmonary resection and CRS-HIPEC, respectively, by comparing overall survival (OS) and disease-free survival (DFS).

Methods

A retrospective review of 49 CLM patients who underwent pulmonary resection, and 52 CPM patients who underwent CRS-HIPEC in a single institution from January 2003 to March 2015, was performed.

Results

The 5-year OS for CLM patients and CPM patients were 59.6 and 40.5%, respectively (p = 0.100), while the 5-year DFS were 24.0 and 14.2%, respectively (p = 0.173). CPM patients had longer median operative time (8.38 vs. 1.75 h, p < 0.001), median hospital stay (13 vs. 5 days, p < 0.001), a higher rate of intensive care unit (ICU) admissions (67.3 vs. 8.2%, p < 0.001), and a higher rate of high-grade complications (17.3 vs. 4.1%, p < 0.001). Multivariate analysis demonstrated that recurrent lung metastasis after metastasectomy was an independent prognostic factor for OS of CLM patients (OR = 0.045, 95%, CL 0.003–0.622, p = 0.021). There were no independent prognostic factors for OS in CPM patients by multivariate analysis. There were no independent prognostic factors for DFS in CLM patients by multivariate analysis, but peritoneal cancer index score, bladder involvement, and higher nodal stage at presentation of the initial malignancy were independent prognostic factors for DFS in CPM patients.

Conclusions

OS and DFS for CPM patients after CRS and HIPEC are comparable to CLM patients after lung resection, although morbidity appears higher. The prognostic factors affecting survival after surgery are different between CPM and CLM patients and must be considered when selecting patients for metastasectomy.

     

The association between the inflammatory response to surgery and postoperative complications in older patients with cancer; a prospective prognostic factor study

BackgroundAccurate prognostic biomarkers would substantially improve surgical planning and decisions making yet no studies have been reported exploring the inflammatory response in surgically treated older patients with cancer. The aim of this study was to explore inflammatory biomarkers as potential prognostic factors for postoperative complications within 30 days in older patients with cancer.MethodPatients 65 years and older undergoing surgery for removal of a solid malignant tumour were included in an observational cohort study. All complications occurring up to 30 days postoperatively were documented prospectively. Inflammatory markers were measured in plasma samples pre- and postoperatively: C-reactive protein (CRP), Interleukin-1 beta (IL-1β), IL-6, IL-10, IL-12, and Tumour necrosis factor-alpha (TNF-α). Associations between inflammatory markers and postoperative complications were explored using logistic regression analysis.ResultsBetween July 2010 and April 2014, plasma samples of 224 patients were collected. Median age was 72 (65–89) years and 116 (51.8%) patients were female. Approximately half of the patients developed postoperative complications (49.6%) of whom 62 patients (55.9%) developed >1 complication. An independent prognostic effect was observed for the inflammatory biomarkers IL-6 and IL-10 for the occurrence of postoperative complications.ConclusionThe perioperative inflammatory response is associated with complications, independently from patient and surgical factors which are also associated with outcome. Research is warranted towards further exploration of the perioperative inflammatory response with the aim to improve perioperative care and outcome, and might help to improve surgical planning and decision making for older patients with cancer.