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  • br A br Years br Netherlands br

    2020-07-27


    A
    Years
    Netherlands
    Moffitt
    B
    Years
    Netherlands
    Moffitt
    C
    Years
    Netherlands
    Moffitt
    and median survival time were similar in young and older patients, al-though bone marrow suppression and hematological toxicity of grade 3 or more was seen more frequently in older patients and older patients tended to need dose reduction of gemcitabine in the first Coelenterazine [24]. The benefits of chemotherapy are clearly linked to baseline performance status, and there is no evidence of a benefit for patients with poor ECOG performance status. On the other hand, with proper supportive care such as e.g. provided with a geriatric oncology program, older pa-tients maintain quite well their functional status despite side effects of chemotherapy [41]. 
    Table 4
    Adjusted HR for patients treated at Moffitt (with Netherlands as reference category), strat-ified for stage, age and type of hospital in the Netherlands.
    Stage 3-years survival Adjusted HR (Moffitt) p-value
    Stratified according to age
    other
    other
    other
    Adjusted for sex, grade, year and age.
    A large number of studies compared younger and older patients who received surgery, however the results with respect to survival are diffi-cult to interpret due to selection bias. Nonetheless these studies show that pancreatoduodenectomy can be safely performed in selected older patients [13,47–50], although some series show that age is one of the determinants for postoperative mortality [10]. Recently there have been unquestioned advancements in patient selection, techniques, perioperative care and management of complications, which resulted in better outcomes for patients who underwent pancreatic resection [51,52]. In the present study, the proportion of patients who underwent surgery in each country was not significantly different between the two cohorts for early stage patients, although this might be due to a low number of patients in this group. For patients with T3 or node positive disease, there was a 10% difference in surgery rate with a higher propor-tion in the Netherlands. This higher proportion of surgery was especially marked for academic hospitals in the Netherlands. This can be explained by centralization of pancreatic cancer care in academic hospitals in the Netherlands. Chronological age is a poor predictor for functional status (physically, mentally and medical) [6] and selecting appropriate ther-apy for older patients remains challenging because of concerns with re-spect to the patients comorbidities, their functional and nutritional status, cognitive function, social support and their expected survival [6,53,54]. An accurate estimation of the expected perioperative morbid-ity and mortality is based on thorough preoperative (geriatric) patient assessment and is central to surgical decision-making with respect to the risks and benefits for an individual patient [33]. As a Whipple resec-tion is a major surgery, treating physicians may hesitate to refer elderly patients for surgery, concerned with the risk of poor post-operative quality of life [42]. There is however a lack of evidence with respect to quality of life studies for older patients with pancreatic cancer, although it is known from the literature that older patients have a higher compli-cation rate and a significant proportion will be admitted to a chronic care facility after surgery. Studies showed that one out of five patients (21%) over the age of 80 years in the first study and 59% in the second were discharged to an outside health care facility and that 51% of the pa-tients developed complications [6,43]. Comorbidities and functional
    reserve might have a key role in the postoperative morbidity (and mor-tality); the presence of comorbidities such as hyperlipidemia, diabetes and coronary artery disease were shown to be possible risk factors for major complications [3,44]. Despite this, one of the few quality of life studies in older patients who underwent pancreatoduodenectomy in a high-volume referral center showed that within 3 months after surgery, quality of life scores were lower yet comparable to their matched con-trols undergoing laparoscopic cholecystectomy [42]. A gradual rather than a rapid recovery process was observed for the older patients, and fatigue was common, lasting for 3 to 6 months after surgery [42]. Other studies have shown a higher prevalence of postoperative depres-sion in the older population [45,46], which was confirmed in this study by a longer emotional recovery in older patients [42].
    The present study showed a higher survival rate for patients treated at Moffitt; these differences seem to be largely explained by differences in treatment strategy between the Netherlands and Moffitt. However, the lower number of patients at Moffitt might have affected the power to detect differences between the cohorts and impact the treatment ef-fect. The assumptions for the instrumental variable methodology were assessed: country was indeed related to the chance of a certain treat-ment strategy and there were large differences between both countries; second, there were no differences in known patient and tumor charac-teristics between the countries that are associated with the outcome, apart from age for T3 or node positive stage. Stratification for age showed that the survival difference was more pronounced for the pa-tients above the age of 75 years. The third assumption, that country should not influence outcome other than through the chance to receive a certain treatment strategy, is difficult to assess with the data. Although differences in health care systems do exist between the Netherlands and Moffitt, patients included in this cohort were of Medicare age. Besides, a previous study comparing both countries, showed that there are no marked differences between patients who resided inside or outside the catchment area of Moffitt Cancer Center [55]. As pancreatic surgical care is centralized in the larger hospitals in the Netherlands, we per-formed a sensitivity analysis to compare the survival stratified by type of hospital. This showed smaller survival differences for patients treated at an academic hospital in the Netherlands compared to Moffitt, espe-cially for patients with T3 or node positive disease. Another drawback in the present comparison is related to the administration of neoadju-vant treatment, which is not part of the Dutch guidelines. Some patients treated at Moffitt with T3 or node positive disease progressed during neoadjuvant chemoradiation and thus became not surgical candidates. Last, for older patients with pancreatic cancer, it is essential to balance quality of life and expected survival. Unfortunately, we had no quality of life information for the patients in these cohorts.