The role of solar forcing upon climate change

Evidence for millennial-scale climate changes during the last 60,000 years has been found in Greenland ice cores and North Atlantic ocean cores. Until now, the cause of these climate changes remained a matter of debate. We argue that variations in solar activity may have played a significant role in forcing these climate changes. We review the coincidence of variations in cosmogenic isotopes (14C and 10Be) with climate changes during the Holocene and the upper part of the last Glacial, and present two possible mechanisms (involving the role of solar UV variations and solar wind/cosmic rays) that may explain how small variations in solar activity are amplified to cause significant climate changes. Accepting the idea of solar forcing of Holocene and Glacial climatic shifts has major implications for our view of present and future climate. It implies that the climate system is far more sensitive to small variations in solar activity than generally believed.

Salvage Robot-Assisted Minimally Invasive Esophagectomy (RAMIE) for T4b Esophageal Cancer After Definitive Chemoradiotherapy

BACKGROUND: Patients with esophageal cancer that invades adjacent structures (cT4b) are precluded from surgery and usually treated with definitive chemoradiotherapy (dCRT). dCRT might result in sufficient downstaging to enable a radical resection, possibly improving survival. This study aimed to assess the perioperative and oncologic outcomes of a salvage robot-assisted minimally invasive esophagectomy (RAMIE) in patients with cT4b esophageal cancer after dCRT. METHODS: Between June 2012 and November 2019, patients who underwent a RAMIE with a gastric conduit reconstruction after completion of dCRT for cT4b esophageal carcinoma were identified from a prospectively maintained surgical database at the University Medical Center Utrecht. RESULTS: In total, 24 patients with a histopathologically confirmed T4b adenocarcinoma or squamous cell carcinoma of the esophagus were included. The adjacent organs involved were the tracheobronchial tree (67%), aorta (21%) or both (13%). No conversions or major intraoperative complications were observed. A radical resection was achieved in 22 patients (92%), and a pathologic complete response was observed in 13 (54%) patients. Postoperative grade 2 or higher complications occurred in 20 patients (83%). The disease-free survival at 24 months was 68% for the patients in whom a radical resection was achieved. CONCLUSION: In patients with cT4b esophageal cancer treated with dCRT followed by a salvage RAMIE, a radical resection rate of 92% was achieved, with acceptable complications and promising survival rates. These results demonstrate the feasibility of a curative surgical treatment for patients with initially irresectable esophageal cancer but underscore the importance of a proper preoperative patient selection

Detection, Treatment, and Survival of Pancreatic Cancer Recurrence in the Netherlands A Nationwide Analysis

OBJECTIVE: To evaluate whether detection of recurrent pancreatic ductal adenocarcinoma (PDAC) in an early, asymptomatic stage increases the number of patients receiving additional treatment, subsequently improving survival. SUMMARY OF BACKGROUND DATA: International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence. METHODS: A nationwide, observational cohort study was performed including all patients who underwent PDAC resection (2014-2016). Prospective baseline and perioperative data were retrieved from the Dutch Pancreatic Cancer Audit. Data on follow-up, treatment, and survival were collected retrospectively. Overall survival (OS) was evaluated using multivariable Cox regression analysis, before and after propensity-score matching, stratified for patients with symptomatic and asymptomatic recurrence. RESULTS: Eight hundred thirty-six patients with a median follow-up of 37 months (interquartile range 30-48) were analyzed. Of those, 670 patients (80%) developed PDAC recurrence after a median follow-up of 10 months (interquartile range 5-17). Additional treatment was performed in 159/511 patients (31%) with symptomatic recurrence versus 77/159 (48%) asymptomatic patients (P < 0.001). After propensity-score matching on lymph node ratio, adjuvant therapy, disease-free survival, and recurrence site, additional treatment was independently associated with improved OS for both symptomatic patients [hazard ratio 0.53 (95% confidence interval 0.42-0.67); P < 0.001] and asymptomatic patients [hazard ratio 0.45 (95% confidence interval 0.29-0.70); P < 0.001]. CONCLUSIONS: Additional treatment of PDAC recurrence was independently associated with improved OS, with asymptomatic patients having a higher probability to receive recurrence treatment. Therefore, standardized postoperative surveillance aiming to detect PDAC recurrence before the onset of symptoms has the potential to improve survival. This provides a rationale for prospective studies on standardized surveillance after PDAC resection

Detecting Interval Distant Metastases With 18F-FDG PET/CT After Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Cancer

PURPOSE: Patients with esophageal cancer can develop distant metastases between the start of neoadjuvant chemoradiotherapy (nCRT) and planned surgery (ie, interval distant metastases). 18F-FDG PET/CT restaging after nCRT detects interval distant metastases in ~8% of patients. This study aimed to identify patients for whom 18F-FDG PET/CT restaging after nCRT could be omitted using an existing prediction model predicting for interval distant metastases or by using clinical stage groups. PATIENTS AND METHODS: Patients with locally advanced esophageal cancer who underwent baseline and restaging 18F-FDG PET/CT, nCRT, and were planned for esophagectomy between 2017 and 2021 were eligible for inclusion in this retrospective study. The primary outcome was the existing model's external performance (ie, discrimination and calibration) for predicting interval distant metastases. The existing model predictors included tumor length, cN status, squamous cell carcinoma histology, and baseline SUVmax. The secondary outcome determined the clinical stage groups (AJCC/UICC eighth edition) for adenocarcinoma and squamous cell carcinoma for which the incidence of interval distant metastases was <10%. RESULTS: In total, 127 patients were included, of whom 17 patients developed interval distant metastases (13%; 95% confidence interval [CI], 8%-21%) and 9 patients were deemed to have false-positive lesions on 18F-FDG PET/CT (7%; 95% CI, 2%-11%). Applying the existing model to this cohort yielded a discriminatory c-statistic of 0.56 (95% CI, 0.40-0.72). The calibration of the existing model was poor (ie, mostly underestimating the actual risk). The incidence of true-positive versus false-positive interval distant metastases for patients with clinical stage II disease was 5% versus 0%; clinical stage III, 14% versus 8%; and clinical stage IVa, 22% versus 9%. CONCLUSIONS: The existing prediction model cannot reliably identify patients at risk for developing interval distant metastases after nCRT for esophageal cancer. Omission of 18F-FDG PET/CT restaging after nCRT could be considered in patients with clinical stage II esophageal cancer

Tumor volume regression during neoadjuvant chemoradiotherapy for esophageal cancer: a prospective study with weekly MRI

Background: Neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer causes tumor regression during treatment. Tumor regression can induce changes in the thoracic anatomy, with smaller target volumes and displacement of organs at risk (OARs) surrounding the tumor as a result. Adaptation of the radiotherapy treatment plan according to volumetric changes during treatment might reduce radiation dose to the OARs, while maintaining adequate target coverage. Data on the magnitude of the volumetric changes and its impact on the thoracic anatomy is scarce. The aim of this study was to assess the volumetric changes in the primary tumor during nCRT for esophageal cancer based on weekly MRI scans.Material and methods: In this prospective study, patients with adeno- or squamous cell carcinoma of the esophagus treated with neoajduvant chemoradiotherapy according to the CROSS regimen (carboplatin + paclitaxel + 23 × 1.8 Gy) were included. Of each patient, six sequential MRI scans were acquired: one prior to nCRT, and five in each subsequent week during nCRT. Tumor volumes were delineated on the transversal T2 weighted images by two radiation oncologists. Volumetric changes were analyzed using linear mixed effects models.Results: A total of 170 MRI scans from 29 individual patients were included. The mean (± standard deviation (SD)) tumor volume at baseline was 45 cm3 (± 23). Tumor volume regression started after the first week of nCRT with a significant decrease in tumor volumes every subsequent week. A decrease to 42 cm3 (91% of initial volume), 38 cm3 (81%), 35 cm3 (77%), and 32 cm3 (72%) was observed in the second, third, fourth and fifth week of nCRT, respectively.Conclusion: Based on weekly MRI scanning during nCRT for esophageal cancer, a considerable decrease in tumor volume was observed during treatment. Volume regression and consequential anatomical changes suggest the possible benefit of adaptive radiotherapy

Nationwide trends in incidence, treatment and survival of pancreatic ductal adenocarcinoma

Background: In recent years, new treatment options have become available for pancreatic ductal adenocarcinoma (PDAC) including 5-fluorouracil, leucovorin, irinotecan and oxaliplatin. The impact hereof has not been assessed in nationwide cohort studies. This population-based study aimed to investigate nationwide trends in incidence, treatment and survival of PDAC. Materials and methods: Patients wi