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  • br c Typically initiated as

    2020-08-12


    c Typically initiated as neo-adjuvant treatment, however detection of liver metastases resulted in cancellation of the surgery.
    Table 3
    Short-term survival for older pancreatic cancer patients, according to stage.
    OS NL (%) OS Moffitt (%) Comparison HR (95%CI)a p-value 1-year Overall Survival
    Netherlands as reference cohort. a Adjusted for age, sex, grade and year.
    b Additionally adjusted for treatment.
    might provide a more accurate evaluation and management plan for older patients. In addition, a more favorable health status of older patients at Moffitt compared with the nationwide Dutch cohort cannot be ruled out.
    4.2. Adjuvant Systemic Treatment
    Differences in the administration of adjuvant chemoradiation and chemotherapy were also observed in the present study, with a larger proportion of patients receiving adjuvant therapy for Moffitt in both early stage and T3 or node positive patients. Decision-making in choosing adjuvant chemotherapy or chemoradiation is complex with contradictory results reported [16,34,35,36,17,18]. The survival benefit of adjuvant chemotherapy after surgical resection was however clearly demonstrated in two RCTs [18,19]. Whereas few older patients were included in RCTs, a recent retrospective series demonstrated a longer survival in patients 75 and older from adjuvant chemoradiation [37]. However, others have also shown that older patients less often receive adjuvant chemotherapy. Many factors contribute to this differ-ence, some are patient driven and some physician driven; factors that are mentioned in studies are the observation that older patients are more often discharged to a rehabilitation facility, and have a longer recovery period after surgery and consequently are less likely to pur-sue further therapy [33]. Besides, older patients who undergo surgical resection with the intention of receiving adjuvant therapy might never receive it because of complications [33]. Studies in older patients are however scarce and more evidence is needed regarding the efficacy and safety of chemotherapy for older patients and for appropriate patient selection [24].
    The difference in receipt of systemic treatment is particularly strik-ing for advanced disease: 85% of Moffitt patients received chemother-apy and/or radiation therapy, versus only 20% of the Dutch patients. A significant difference in one year overall survival was observed for these patients: 27.7% (21.1–34.6) for patients at Moffitt versus 8.2% (6.9–9.8). This might be due to various factors; one PEG300 might be the differences in cultural perception of the benefit of giving pallia-tive chemotherapy to pancreatic cancer patients. Transcultural percep-tions were explored in detail between French and American patients [38]. Interestingly enough, whereas older non-cancer patients were less interested in moderate chemotherapy on the European side, nearly 
    all older cancer patients were interested in the option on either side of the Atlantic Ocean. It might however be that Dutch patients more often declined chemotherapy, or experienced more often complications after which the chemotherapy was omitted, or physicians might have been more reserved to prescribe chemotherapy; these details are how-ever at this moment unknown in the cancer registry data. Given the associated survival benefit, this indicates that there might be a need for a reconsideration of the general avoidance of chemotherapy observed in our cohort of Dutch patients. Although one might hypothe-size some referral bias at Moffitt, it should be noted that in Dutch academic centers, only 54% of patients with advanced disease did receive systemic treatment. Therefore in our opinion, this would only explain a small proportion of the inter-country variance. The Moffitt practice appears representative of the practice at other American Com-prehensive Cancer Centers with geriatric oncologists. A recent series in pancreatic cancer patients with metastatic disease showed that 65% of patients above age 65 did receive chemotherapy, compared with 75% of younger ones [39]. In that series, receipt of chemotherapy, preferably with two agents, was also associated with a survival benefit at all ages. It might have been that patients at Moffitt received more often a combina-tion therapy as compared to the Netherlands during the included years; future studies might study differences in chemotherapy regimens, adherence and outcomes specifically for older patients. Unfortunately, we had no details with respect to the chemotherapy regimens used in the present study or whether patients were included in clinical trials.
    Whereas survival is improved with palliative systemic treatment, this benefit might be counterbalanced by quality of life concerns. FOLFIRINOX was studied in patients below the age of 76 with ECOG 0–1(median 61) and has significant side effects. However, a recent se-ries showed that 57% of the patients needed a dose reduction; but that this reduction did not impact the overall survival (11.7 (6.9–16.4 com-pared to 16.6 (0.37–32.8; p = .69) months without dose reduction in patients aged 70 and older, which is comparable to that obtained in younger patients [37]. However this comes at the cost of a greater im-pact on quality of life as a larger proportion experienced grade 3 neuro-toxicity, and most older patients are treated with gemcitabine or a gemcitabine doublet. Studies for older patients are also scarce in this area [24]. One retrospective study compared older and younger patients who received gemcitabine and patients under best supportive care [24]. The response rate, disease stabilization, improvement of tumor makers