External validation of three lymph node ratio-based nomograms predicting survival using an international cohort of patients with resected pancreatic head ductal adenocarcinoma

IntroductionLymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms using an international cohort.Materials and methodsConsecutive PDAC patients who underwent upfront pancreatoduodenectomy from six centers (Europe/USA) were collected (2000–2017). Patients with metastases, R2 resection, missing LNR data, and who died within 90 postoperative days were excluded. The updated Amsterdam nomogram, the nomogram by Pu et al., and the nomogram by Li et al. were selected. For the validation, calibration, discrimination capacity, and clinical utility were assessed.ResultsAfter exclusion of 176 patients, 1′113 patients were included. Median overall survival (OS) of the cohort was 23 months (95% CI: 21–25).For the three nomograms, Kaplan-Meier curves showed significant OS diminution with increasing scores (p < 0.01). All nomograms showed good calibration (non-significant Hosmer-Lemeshow tests). For the Amsterdam nomogram, area under the ROC curve (AUROC) for 3-year OS was 0.64 and 0.67 for 5-year OS. Sensitivity and specificity for 3-year OS prediction were 65% and 59%. Regarding the nomogram by Pu et al., AUROC for 3- and 5-year OS were 0.66 and 0.70. Sensitivity and specificity for 3-year OS prediction were 68% and 53%. For the Li nomogram, AUROC for 3- and 5-year OS were 0.67 and 0.71, while sensitivity and specificity for 3-year OS prediction were 63% and 60%.ConclusionThe three nomograms were validated using an international cohort. Those nomograms can be used in clinical practice to evaluate survival after pancreatoduodenectomy for PDAC.     

Development and external validation of a prediction model for survival in patients with resected ampullary adenocarcinoma

IntroductionAmpullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC.Materials and methodsAn international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006–2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score.ResultsOverall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73–0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73–0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival.ConclusionA prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.     

Preoperative misdiagnosis of pancreatic and periampullary cancer in patients undergoing pancreatoduodenectomy: A multicentre retrospective cohort study

IntroductionWhereas neoadjuvant chemo(radio)therapy is increasingly used in pancreatic cancer, it is currently not recommended for other periampullary (non-pancreatic) cancers. This has important implications for the relevance of the preoperative diagnosis for pancreatoduodenectomy. This retrospective multicentre cohort study aimed to determine the frequency of clinically relevant misdiagnoses in patients undergoing pancreatoduodenectomy for pancreatic or other periampullary cancer.MethodsData from all consecutive patients who underwent a pancreatoduodenectomy between 2014 and 2018 were obtained from the prospective Dutch Pancreatic Cancer Audit. The preoperative diagnosis as concluded by the multidisciplinary team (MDT) meeting was compared with the final postoperative diagnosis at pathology to determine the rate of clinically relevant misdiagnosis (defined as missed pancreatic cancer or incorrect diagnosis of pancreatic cancer).ResultsIn total, 1244 patients underwent pancreatoduodenectomy of whom 203 (16%) had a clinically relevant misdiagnosis preoperatively. Of all patients with a final diagnosis of pancreatic cancer, 13% (87/679) were preoperatively misdiagnosed as distal cholangiocarcinoma (n = 41, 6.0%), ampullary cancer (n = 27, 4.0%) duodenal cancer (n = 16, 2.4%), or other (n = 3, 0.4%). Of all patients with a final diagnosis of periampullary (non-pancreatic) cancer, 21% (116/565) were preoperatively incorrectly diagnosed as pancreatic cancer. Accuracy of preoperative diagnosis was 84% for pancreatic cancer, 71% for distal cholangiocarcinoma, 73% for ampullary cancer and 73% for duodenal cancer. A prediction model for the preoperative likelihood of pancreatic cancer (versus other periampullary cancer) prior to pancreatoduodenectomy demonstrated an AUC of 0.88.DiscussionThis retrospective multicentre cohort study showed that 16% of patients have a clinically relevant misdiagnosis that could result in either missing the opportunity of neoadjuvant chemotherapy in patients with pancreatic cancer or inappropriate administration of neoadjuvant chemotherapy in patients with non-pancreatic periampullary cancer. A preoperative prediction model is available on www.pancreascalculator.com.     

A prognostic nomogram to predict overall survival in patients with platinum-sensitive recurrent ovarian cancer

BackgroundPatients with platinum-sensitive recurrent ovarian cancer have variable prognosis and survival. We extend previous work on prediction of progression-free survival by developing a nomogram to predict overall survival (OS) in these patients treated with platinum-based chemotherapy.Patients and methodsThe nomogram was developed using data from the CAELYX in Platinum-Sensitive Ovarian Patients (CALYPSO) trial. Multivariate proportional hazards models were generated based on pre-treatment characteristics to develop a nomogram that classifies patient prognosis based on OS outcome. We also developed two simpler models with fewer variables and conducted model validations in independent datasets from AGO-OVAR Study 2.5 and ICON 4. We compare the performance of the nomogram with the simpler models by examining the differences in the C-statistics and net reclassification index (NRI).ResultsThe nomogram included six significant predictors: interval from last platinum chemotherapy, performance status, size of the largest tumour, CA-125, haemoglobin and the number of organ sites of metastasis (C-statistic 0.67; 95% confidence interval 0.65–0.69). Among the CALPYSO patients, the median OS for good, intermediate and poor prognosis groups was 56.2, 31.0 and 20.8 months, respectively. When CA-125 was not included in the model, the C-statistics were 0.65 (CALYPSO) and 0.64 (AGO-OVAR 2.5). A simpler model (interval from last platinum chemotherapy, performance status and CA-125) produced a significant decrease of the C-statistic (0.63) and NRI (26.4%, P < 0.0001).ConclusionsThis nomogram with six pre-treatment characteristics improves OS prediction in patients with platinum-sensitive ovarian cancer and is superior to models with fewer prognostic factors or platinum chemotherapy free interval alone. With independent validation, this nomogram could potentially be useful for improved stratification of patients in clinical trials and also for counselling patients.     

Delaying chemoradiation until after completion of adjuvant chemotherapy for pancreatic cancer may not impact local control

BackgroundTiming of administration of adjuvant chemoradiation (CRT) for pancreatic cancer has varied across studies. To date, the impact of timing of adjuvant CRT on long-term outcomes has not been evaluated. This study evaluates the effect of timing of adjuvant CRT on locoregional control (LRC) and overall survival (OS).Methods and MaterialsWe performed a review of 159 patients with resected pancreatic adenocarcinoma who received adjuvant CRT between 1998 and 2010. Median dose of CRT was 50.4 Gy. The primary study variable was timing of CRT, dichotomized as immediate CRT versus delayed CRT. Consistent with Radiation Therapy Oncology Group (RTOG) 9704, immediate chemoradiation was defined as after ≤ 1 cycle of chemotherapy, whereas delayed CRT was defined as after > 1 cycle. Cox multivariate analysis (MVA) was performed.ResultsMedian follow-up was 55 months. Seventy-four percent of patients received immediate CRT, and 26% patients received delayed CRT. Patients treated with delayed CRT were more likely to receive adjuvant gemcitabine (100% vs 53%; P < .001). Timing of adjuvant CRT was not associated with LRC or OS on univariate or MVA. Preoperative carcinoembryonic antigen ≥ 1.3 ng/mL (hazard ratio, 3.18; P = .017) and positive margins (hazard ratio, 5.35; P < .001) were associated with lower rates LRC on MVA. Higher lymph node positivity ratio and not receiving adjuvant gemcitabine were independently associated with worse OS.ConclusionsTiming of adjuvant CRT for resectable pancreatic cancer may not significantly affect LRC or OS. These findings support the ongoing RTOG 0848 trial design, and provide reassurance that delaying CRT until completion of chemotherapy should not significantly impact LRC.     

Development and Validation of a Breast Cancer Risk Prediction Model for Thai Women: A Cross-Sectional Study

Background: Breast cancer risk prediction models are widely used in clinical practice. They should be useful in identifying high risk women for screening in limited-resource countries. However, previous models showed poor performance in derived and validated settings. Therefore, we aimed to develop and validate a breast cancer risk prediction model for Thai women. Materials and Methods: This cross-sectional study consisted of derived and validation phases. Data collected at Ramathibodi and other two hospitals were used for deriving and externally validating models, respectively. Multiple logistic regression was applied to construct the model. Calibration and discrimination performances were assessed using the observed/expected ratio and concordance statistic (C-statistic), respectively. A bootstrap with 200 repetitions was applied for internal validation. Results: Age, menopausal status, body mass index, and use of oral contraceptives were significantly associated with breast cancer and were included in the model. Observed/expected ratio and C-statistic were 1.00 (95% CI: 0.82, 1.21) and 0.651 (95% CI: 0.595, 0.707), respectively. Internal validation showed good performance with a bias of 0.010 (95% CI: 0.002, 0.018) and C-statistic of 0.646(95% CI: 0.642, 0.650). The observed/expected ratio and C-statistic from external validation were 0.97 (95% CI: 0.68, 1.35) and 0.609 (95% CI: 0.511, 0.706), respectively. Risk scores were created and was stratified as low (0-0.86), low-intermediate (0.87-1.14), intermediate-high (1.15-1.52), and high-risk (1.53-3.40) groups. Conclusions: A Thai breast cancer risk prediction model was created with good calibration and fair discrimination performance. Risk stratification should aid to prioritize high risk women to receive an organized breast cancer screening program in Thailand and other limited-resource countries.     

Adjuvant chemotherapy and relative survival of patients with stage II colon cancer – A EURECCA international comparison between the Netherlands,Denmark, Sweden,England, Ireland,Belgium, and Lithuania

BackgroundThe aim of the present EURECCA international comparison is to compare adjuvant chemotherapy and relative survival of patients with stage II colon cancer between European countries.MethodsPopulation-based national cohort data (2004–2009) from the Netherlands (NL), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), and Belgium (BE) were obtained, as well as single-centre data from Lithuania. All surgically treated patients with stage II colon cancer were included. The proportion of patients receiving adjuvant chemotherapy was calculated and compared between countries. Besides, relative survival was calculated and compared between countries.ResultsOverall, 59,154 patients were included. The proportion of patients receiving adjuvant chemotherapy ranged from 7.1% to 29.0% (p < 0.001). Compared with NL, a better adjusted relative survival was observed in SE (stage II: relative excess risks (RER) 0.53, 95% confidence interval (CI) 0.44–0.64; p < 0.001), and BE (stage II: RER 0.84, 95% CI 0.76–0.92; p < 0.001), and in IE for patients with stage IIA disease (RER 0.80, 95% CI 0.65–0.98; p = 0.03).ConclusionThe proportion of patients with stage II colon cancer receiving adjuvant chemotherapy varied largely between seven European countries. No clear linear pattern between adjuvant chemotherapy and adjusted relative survival was observed. Compared with NL, SE and BE showed an improved adjusted relative survival for stage II disease, and IE for patients with stage IIA disease only. Further research into selection criteria for adjuvant chemotherapy could eventually lead to individually tailored, optimal treatment of patients with stage II colon cancer.     

Survival benefit of adjuvant chemoradiotherapy for positive or close resection margin after curative resection of pancreatic adenocarcinoma

BackgroundThis study was conducted to identify patients who may benefit from adjuvant chemoradiotherapy (CRT) for positive or close resection margin (RM) after curative resection of pancreatic adenocarcinoma.MethodsFrom 2004 to 2015, total of 472 patients with pancreatic adenocarcinoma underwent curative resection. After excluding patients with RM > 2 mm or unknown, remaining 217 patients were retrospectively analyzed. Forty-six (21.2%) patients were treated with adjuvant chemotherapy alone (CTx; mainly gemcitabine-based), 142 (65.4%) with adjuvant CRT (mainly upfront), and 29 (13.4%) patients didn’t receive any adjuvant therapy (noTx group).ResultsLocoregional recurrence rate was significantly lower in the CRT group (43.7%) than in the CTx group (71.7%) or noTx group (65.5%) (p = 0.001). Significant survival benefits of CRT over CTx (HR 0.602, p = 0.020 for overall survival (OS); HR 0.599, p = 0.016 for time to any recurrence (TTR)) were demonstrated in multivariate analysis. CRT group had more 5-year survivors than other groups. In the subgroup analysis, such benefits of adjuvant CRT over CTx was observed only in patients with head tumor & vascular RM > 0.5 mm, but not in patients with body/tail tumor or vascular RM ≤ 0.5 mm. In the CRT group, radiation dose≥54 Gy was significantly associated with better TTR and OS.ConclusionsAdjuvant CRT could improve TTR and OS compared to adjuvant CTx alone in patients with close RM under 2 mm. Radiation dose escalation may be beneficial when feasible. Modern CRT regimen–based randomized evidence is needed for these high-risk patients.     

Presence of low-grade IPMN at the pancreatic transection margin does not have prognostic significance after resection of IPMN-associated pancreatic adenocarcinoma

IntroductionResection margin status is a well-established prognosticator in pancreatic cancer. The prognostic impact of IPMN dysplasia at the pancreatic transection margin in IPMN-associated carcinoma (IPMN-Ca) remains unclear, hence institutional practices on additional resections vary.MethodsPatients undergoing partial pancreatectomy or attempted partial pancreatectomy converted to total pancreatectomy for IPMN-Ca between 04/2002 and 12/2018 were identified. Final pathology of the definitive pancreatic transection margin was identified. The association between the presence of IPMN dysplasia at the margin and overall survival (OS) was assessed.ResultsOf 302 patients with IPMN-Ca, 181 (59.9%) patients received partial pancreatoduodenectomy, 61 (20.2%) distal pancreatectomy, and 60 (19.9%) were converted to total pancreatectomy. Median OS was 98.6 months in R0 (≥1 mm), 39.3 months in R1 (<1 mm), and 22.0 months in R1(direct) resected patients, respectively (p < 0.0001). No IPMN dysplasia at the definitive margin was present in 103 (34.1%), low-grade in 131 (43.4%), and high-grade/R1 in 8 (2.6%) patients. Low-grade dysplasia or total pancreatectomy were not associated with shorter OS compared to dysplasia-free margin across the entire cohort. Sensitivity analyses confirmed a lack of prognostic relevance of low-grade IPMN dysplasia at the pancreatic margin in R0 resected IPMN-Ca and in R0 resected UICC stage IA/IB IPMN-Ca.ConclusionsLow-grade IPMN at the transection margin is not associated with shorter overall survival after partial pancreatectomy for IPMN-Ca. Additional resections for low-grade dysplasia, up to total pancreatectomy do not result in a survival benefit and should be omitted. Due to limited sample size, high-grade dysplasia could not be analyzed.     

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.     

Progression-free survival as a surrogate for overall survival in first-line chemotherapy for advanced pancreatic cancer

BackgroundOverall survival (OS), as the primary end-point in first-line chemotherapy trials, requires a prolonged follow-up time and may be confounded by subsequent regimens. This study aimed to evaluate the correlation between OS and surrogate end-points (progression-free survival [PFS], response rate and disease control rate), and to identify a potential surrogate for OS in advanced pancreatic cancer.MethodsBased on an electronic search, we identified randomized controlled phase II and III trials of first-line chemotherapy for advanced pancreatic cancer. Correlation analyses were performed between surrogate end-points and OS, and between improvements in surrogates and those in OS.ResultsFifty trials (II/II–III/III, 17/2/31) with 111 treatment arms were identified, and 15,906 patients were analysed. PFS was most strongly correlated with OS (correlation coefficient, 0.76). Weighted linear regression models revealed the greatest determinant coefficient of 0.84 between the hazard ratio (HR) of the experimental arms compared with the control arms of PFS and that of OS. The approximate equation was log HR_OS = 0.01 + 0.77 × log HR_PFS, indicating that risk reduction of OS via chemotherapy would translate into a 77% risk reduction of PFS. The surrogacy of PFS for OS was robust throughout our subgroup analyses: e.g., biologic versus non-biologic regimens, locally advanced versus metastatic disease.ConclusionsThe surrogacy of PFS for OS in pancreatic cancer was validated. Therefore, the use of PFS as the primary end-point in clinical trials could facilitate the early introduction of new effective chemotherapy regimens into clinical practice.     

Comparative Effectiveness of Total Neoadjuvant Therapy Versus Standard Adjuvant Chemotherapy for Locally Advanced Rectal Cancer

IntroductionThe use of total neoadjuvant therapy (TNT) for locally advanced rectal cancer has been increasing in recent years, but the long-term overall survival characteristics of this approach is currently unknown.MethodsWe performed a retrospective study of patients with clinical stage II/III rectal cancer within the National Cancer Database. Patients who received TNT (defined as chemotherapy, followed by CRT, followed by surgery) were propensity score matched to patients who received adjuvant therapy (defined as CRT, followed by surgery, followed by chemotherapy). We compared overall survival (OS) and rates of pathologic complete response (pCR) between the 2 arms.ResultsOf the 4300 patients in our cohort, 3502 (81%) received adjuvant therapy and 798 (19%) received TNT. At baseline, patients who received TNT were more likely to have higher clinical T and N stages (P< .001). The 5-year OS was 77% for both TNT and adjuvant therapy patients (hazard ratio [HR] 1.06, 95% confidence interval [CI], 0.88-1.28, P = .57). After propensity score matching and adjusting for potential confounders, there were no significant differences in OS (HR_adj 1.00, 95% CI, 0.71-1.40, P = .99). After propensity score matching, there were higher pCR rates among TNT patients (16.1%) compared to adjuvant therapy patients (12.0%) (P = .037).ConclusionIn this observational study, we found TNT was not associated with a lower OS compared to standard adjuvant chemotherapy. This finding potentially reassures clinicians choosing TNT as an alternative to adjuvant chemotherapy. However, future prospective data are needed to confirm these findings.     

Influence of age and comorbidity on prognosis and application of adjuvant chemotherapy in elderly Japanese patients with colorectal cancer: A retrospective multicentre study

BackgroundAdjuvant therapy for colorectal cancer (CRC) in patients aged ≥75 years is supported by inadequate evidence, although such patients are increasing in number worldwide.Patients and methodsWe assessed the influence of age and comorbidities on the prognosis of CRC in elderly patients using pooled data by the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer. In total, 4598 patients (3304 with colon cancer and 1294 with rectal cancer) who underwent curative surgery from 2004 to 2006 were analysed with respect to age, Charlson comorbidity score (CS), tumour marker positivity, adjuvant therapy and prognosis.ResultsThe number of patients aged <64, 65–74 and >75 years was 2007 (44%), 1614 (35%) and 977 (21%), respectively. Tumour location, tumour marker positivity, clinical stage, performance of adjuvant therapy, CS and overall survival (OS) were significantly different among these age groups (P < 0.0001). Among patients aged ≥75 years with stage III CRC, 35% with colon cancer and 21% with rectal cancer received adjuvant therapy; these proportions were much lower than those in younger patients. Application of adjuvant therapy was dependent on the CS in patients aged ≤74 years, but not in older patients. Sex, the carcinoembryonic antigen concentration and adjuvant therapy were significantly associated with OS in elderly patients with stage III CRC.ConclusionAge and comorbidities worsened the OS of patients with CRC who underwent curative surgery. However, patients aged ≥75 years were undertreated regardless of their CS despite the possibility of OS improvement by adjuvant therapy.     

A prediction model for treatment decisions in high-grade extremity soft-tissue sarcomas: Personalised sarcoma care (PERSARC)

BackgroundTo support shared decision-making, we developed the first prediction model for patients with primary soft-tissue sarcomas of the extremities (ESTS) which takes into account treatment modalities, including applied radiotherapy (RT) and achieved surgical margins. The PERsonalised SARcoma Care (PERSARC) model, predicts overall survival (OS) and the probability of local recurrence (LR) at 3, 5 and 10 years.AimDevelopment and validation, by internal validation, of the PERSARC prediction model.MethodsThe cohort used to develop the model consists of 766 ESTS patients who underwent surgery, between 2000 and 2014, at five specialised international sarcoma centres. To assess the effect of prognostic factors on OS and on the cumulative incidence of LR (CILR), a multivariate Cox proportional hazard regression and the Fine and Gray model were estimated. Predictive performance was investigated by using internal cross validation (CV) and calibration. The discriminative ability of the model was determined with the C-index.ResultsMultivariate Cox regression revealed that age and tumour size had a significant effect on OS. More importantly, patients who received RT showed better outcomes, in terms of OS and CILR, than those treated with surgery alone. Internal validation of the model showed good calibration and discrimination, with a C-index of 0.677 and 0.696 for OS and CILR, respectively.ConclusionsThe PERSARC model is the first to incorporate known clinical risk factors with the use of different treatments and surgical outcome measures. The developed model is internally validated to provide a reliable prediction of post-operative OS and CILR for patients with primary high-grade ESTS.Level of significancelevel III.     

The GLIM criteria as an effective tool for survival prediction in gastric cancer patients

BackgroundThe Global Leadership Initiative on Malnutrition released a new version of the malnutrition criteria (GLIM criteria). To investigate the influence of the GLIM criteria on the long-term efficacy of radical gastric cancer surgery and establish a nomogram to predict the long-term prognosis of patients with gastric cancer.MethodsA retrospective analysis of 1121 patients with gastric cancer in our department from 2010 to 2013 was performed. A nomogram was established to predict overall survival (OS) based on the GLIM criteria. Patients were divided into the low-risk group (LRG) and high-risk group (HRG) based on the established nomogram.ResultsMultivariate Cox regression analyses showed that GLIM criteria was an independent risk factor for the 5-year OS (HR = 1.768, Cl:1.341–2.329, p < 0.001). The C index, AUC and Time-ROC of the nomogram were significantly better than that of GLIM criteria and traditional criteria. The 5-year OS of patients receiving adjuvant chemotherapy in the high-risk group was significantly higher than that of patients without chemotherapy (45.77% vs. 24.73%,p < 0.001).ConclusionsThe GLIM criteria independently influence the long-term outcome of patients after radical gastric cancer surgery. The established nomogram can predict the long-term survival of patients with gastric cancer, and postoperative adjuvant chemotherapy for HRG can significantly improve the 5-year OS of patients.     

Neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian cancer: GOTIC-019 study

Introduction

Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice.

Patients and methods

We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy.

Results

Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93).

Conclusions

NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.

     

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.     

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.     

S100A2 is a predictive biomarker of adjuvant therapy benefit in pancreatic adenocarcinoma

BackgroundPrognosis of patients with pancreatic adenocarcinoma (PAC) remains poor. S100A2 has been recently suggested as a negative prognostic biomarker in PAC. We aimed to investigate its prognostic and/or predictive value in a large independent multicentric cohort of patients with resected PAC.MethodsSequential samples of 471 patients were retrospectively collected; 142 patients did not receive adjuvant treatment (30%) and 329 (70%) received an adjuvant treatment. We measured protein levels of S100A2 by semiquantitative immunohistochemistry with tissue microarrays and correlated with patients’ overall survival (OS) and disease-free survival (DFS).ResultsS100A2 protein status was obtained in 462 (98%) patients. Its expression was low, moderate or high in 59%, 12% and 2% of cases, respectively. It was not correlated with DFS or OS in the whole population, neither in the subgroup of patients who did not receive adjuvant treatment. However among patients who received an adjuvant therapy, moderate/high levels of S100A2 were significantly associated with longer OS and DFS in multivariate analysis (hazard ratios of 0.63, p = 0.022 and 0.67, p = 0.017, respectively), whereas low S100A2 was not. Interaction tests for adjuvant therapy were statistically significant both for the OS and the DFS (p = 0.001 and p = 0.023, respectively). On multivariate analysis, S100A2 retained independent predictive values (OS: p < 0.001, DFS: p = 0.003) with a significant benefit of adjuvant therapy for those patients with moderate/high S100A2.ConclusionsS100A2 expression predicts longer DFS and OS in patients treated with adjuvant therapy and should be evaluated as a predictive biomarker.     

Determining the role of adjuvant therapy in Invasive Intraductal Papillary Mucinous Neoplasms; a systematic review and meta-analysis

BackgroundConflicting evidence exists regarding the role of adjuvant therapy for Invasive Intraductal Papillary Mucinous Neoplasms (i-IPMN). This meta-analysis assessed whether adjuvant therapy improves Overall Survival (OS) in patients with resected i-IPMN.MethodsA systematic review and meta-analysis was performed. The primary endpoint was the effect of adjuvant therapy on OS. Secondary endpoint evaluated adjuvant therapy with regard to nodal disease, positive resection margins, tumour grade and differentiation. A meta-analysis of pooled hazard ratios (HRs) with an inverse variance and a random-effects model was performed. Risk of bias was determined with the GRADE approach and MINORS criteria.ResultsTen articles with a total of 3252 patients were included. No statistically significant difference in the OS was noted with adjuvant therapy for i-IPMN in the entire cohort (HR = 1; 95% CI = 0.75–1.35; P = 0.98). However, a survival benefit was noted in a subgroup of patients with an aggressive disease phenotype; nodal involvement (HR = 0.56; 95% CI = 0.39–0.79; P = 0.001) and advanced staged tumours (≥stage 2, HR = 1.42; 95% CI = 1.11–1.82; P = 0.005)ConclusionsThe concurrent evidence base for adjuvant therapy for i-IPMN is limited. After acknowledging the limitations of the data, the current literature suggests that adjuvant therapy should be reserved for patients with resected i-IPMN that have adverse tumour biology.