Prediction of survival in patients with oesophageal or junctional cancer receiving neoadjuvant chemoradiotherapy and surgery.

BACKGROUND: The value of conventional prognostic factors is unclear in the era of multimodal treatment for oesophageal cancer. This study aimed to quantify the impact of neoadjuvant chemoradiotherapy (nCRT) and surgery on well established prognostic factors, and to develop and validate a prognostic model. METHODS: Patients treated with nCRT plus surgery were included. Multivariable Cox modelling was used to identify prognostic factors for overall survival. A prediction model for individual survival was developed using stepwise backward selection. The model was internally validated leading to a nomogram for use in clinical practice. RESULTS: Some 626 patients who underwent nCRT plus surgery were included. In the multivariable model, only pretreatment cN category and ypN category were independent prognostic factors. The final prognostic model included cN, ypT and ypN categories, and had moderate discrimination (c-index at internal validation 0·63). CONCLUSION: In patients with oesophageal or oesophagogastric cancer treated with nCRT plus surgery, overall survival can best be estimated using a prediction model based on cN, ypT and ypN categories. Predicted survival according to this model showed only moderate correlation with observed survival, emphasizing the need for new prognostic factors to improve survival prediction.

Pattern of recurrence in patients with a pathologically complete response after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) and surgery is a widely used treatment for locally advanced resectable oesophageal cancer, with 20-50 per cent of patients having a pathological complete response (pCR). Disease, however, still recurs in 20-30 per cent of these patients. The aim of this study was to assess the pattern of recurrence in patients with a pCR after nCRT and surgery. METHODS: All patients with a pCR after nCRT and surgery included in the phase II and III CROSS (ChemoRadiotherapy for Oesophageal followed by Surgery Study) trials (April 2001 to December 2008) and after the CROSS trials (September 2009 to October 2017) were identified. The site of recurrence was compared with the applied radiation and surgical fields. Outcomes were median time to recurrence, and overall and progression-free survival. RESULTS: A total of 141 patients with a median follow-up of 100 (i.q.r. 64-134) months were included. Some 29 of 141 patients (20,6 per cent) developed recurrence. Of these, four had isolated locoregional recurrence, 15 had distant recurrence only, and ten had both locoregional and distant recurrence. Among the 14 patients with locoregional recurrences, five had recurrence within the radiation field, seven outside the radiation field, and two at the border. Median time to recurrence was 24 (10-62) months. The 5-year overall survival rate was 74 per cent and the recurrence-free survival rate was 70 per cent. CONCLUSION: Despite good overall survival, recurrence still occurred in 21 per cent of patients. Most recurrences were distant, outside the radiation and surgical fields.

Long-term outcomes 1-20 years after autotransplantation of teeth: clinical and radiographic evaluation of 66 premolars and 8 molars.

In this retrospective study we investigated the long-term survival of autotransplanted premolars and molars with incompletely developed roots. The presence of the transplanted teeth and their outcome after autotransplantation was ascertained from clinical and radiographic evaluation by a maxillofacial surgeon or dentist. Kaplan Meier survival curves were estimated for the total population and for the two groups (premolars and molars). Fifty-one patients with 74 transplanted teeth were included, and the median duration of follow-up was 10 (range 1-20) years. Four of 66 premolars and one of 8 molars were removed and the cumulative survival was 95.4% (95% CI 90.3 to 100). The difference in survival between the premolars and molars was not significant. These results show that the long-term survival of autotransplanted teeth is good. Replacement of a single tooth by autotransplantation should therefore always be considered and is preferred when a suitable donor tooth is available.

The importance of glycine-30 for enzymatic activity of phospholipase A2.

The nearly conserved glycine-30 in porcine pancreatic phospholipase A2 has been replaced by serine. The resulting mutant G30S was expressed in Escherichia coli, purified and characterized. The mutation caused a significant drop in enzymatic activity towards monomeric and aggregated substrates, but had a limited effect on substrate binding. In contrast the affinity for calcium ions, the essential cofactor, was reduced 10-fold. The reduced enzymatic activity is attributed to a reduced stabilization of the transition state. The results are discussed in view of naturally occurring inactive phospholipase A2 homologues from snake venom.

Induction chemotherapy followed by surgery for advanced oesophageal cancer.

BACKGROUND: Patients with locoregionally advanced oesophageal tumours or disputable distant metastases are referred for induction chemotherapy with the aim to downstage the tumour before an oesophagectomy is considered. STUDY DESIGN: Patients who underwent induction chemotherapy between January 2005 and December 2012 were identified from an institutional database. Treatment plan was discussed in the multidisciplinary team. Response to chemotherapy was assessed by CT. Survival was calculated using the Kaplan Meier method. Uni- and multivariable analyses were performed to identify prognostic factors for survival. RESULTS: In total 124 patients received induction chemotherapy mainly for locoregionally advanced disease (n = 80). Surgery was withheld in 35 patients because of progressive disease (n = 16) and persistent unresectability (n = 19). The median overall survival of this group was 13 months (IQR: 8-19). The remaining 89 patients underwent surgery of which 13 still had unresectable tumour or distant metastases. Of the 76 patients that underwent an oesophagectomy, 50 patients had tumour free resection margins (66%) with an estimated 5-year survival of 37%. A positive resection margin (HR 4.148, 95% CI 2.298-7.488, p < 0.0001) was associated with a worse survival in univariable analysis, but only pathological lymph node status with increasing hazard ratio's (6.283-10.283, p = 0.001) remained significant after multivariable analysis. CONCLUSION: Induction chemotherapy downstages the tumour and facilitates a radical oesophagectomy in patients with advanced oesophageal cancer. Pathological lymph node status is an independent prognostic factor for overall survival.