Prioritization and Resource Allocation in the Context of the COVID-19 Pandemic: Recommendations for Colorectal and Pancreatic Cancer in Germany.

In the context of the COVID-19 pandemic, there has been a scarcity of resources with various effects on the care of cancer patients. This paper provides an English summary of a German guideline on prioritization and resource allocation for colorectal and pancreatic cancer in the context of the pandemic. Based on a selective literature review as well as empirical and ethical analyses, the research team of the CancerCOVID Consortium drafted recommendations for prioritizing diagnostic and treatment measures for both entities. The final version of the guideline received consent from the executive boards of nine societies of the Association of Scientific Medical Societies in Germany (AWMF), 20 further professional organizations and 22 other experts from various disciplines as well as patient representatives. The guiding principle for the prioritization of decisions is the minimization of harm. Prioritization decisions to fulfill this overall goal should be guided by (1) the urgency relevant to avoid or reduce harm, (2) the likelihood of success of the diagnostic or therapeutic measure advised, and (3) the availability of alternative treatment options. In the event of a relevant risk of harm as a result of prioritization, these decisions should be made by means of a team approach. Gender, age, disability, ethnicity, origin, and other social characteristics, such as social or insurance status, as well as the vehemence of a patient's treatment request and SARS-CoV-2 vaccination status should not be used as prioritization criteria. The guideline provides concrete recommendations for (1) diagnostic procedures, (2) surgical procedures for cancer, and (3) systemic treatment and radiotherapy in patients with colorectal or pancreatic cancer within the context of the German healthcare system.

Neglected geriatric assessment and overtreatment of older patients with pancreatic cancer - Results from a prospective phase IV clinical trial.

BACKGROUND: Older patients with metastatic pancreatic cancer may suffer increased toxicity from intensive chemotherapy. Treatment individualization by geriatric assessment (GA) might improve functional outcome. METHODS: We performed a multicenter, phase IV, open label trial in patients ≥70 years with metastatic pancreatic adenocarcinoma. Patients underwent GA and were assigned to one of three categories based on their scores: Go-Go, Slow-Go, or Frail. These categories were intended to guide physician's treatment decisions when choosing to treat patients with nab-paclitaxel/gemcitabine (arm A), gemcitabine (arm B), or best supportive care (arm C). Primary objective was a stable (loss of five points or less) Barthel's Activities of Daily Living (ADL) score during chemotherapy; secondary endpoints included GA scores during therapy, safety, quality of life, response and survival rates. RESULTS: Thirty-two patients were enrolled in the trial in six centers in Germany (out of 135 planned), resulting in termination due to low recruitment. Fifteen patients were allocated to nab-paclitaxel/gemcitabine, fifteen to gemcitabine, and two to best supportive care by their physicians, although according to their GA scores 29 patients (91%) were categorized as Slow-Go and three (9%) as Go-Go. Thus, fifteen of 32 (47%) patients were misclassified and given a course of treatment inconsistent with their GA scores. Median progression-free survival (PFS) were 3.3 months and 9.1 months and median time to quality-of-life deterioration 13 days and 29 days in the nab-paclitaxel/gemcitabine and gemcitabine monotherapy arms, respectively. Serious adverse events were reported in 11 (78.6%) patients in the nab-paclitaxel/gemcitabine and 8 (53.3%) patients in the gemcitabine arm. CONCLUSIONS: Clinical evaluations by investigators differed markedly from geriatric assessments, leading to potential overtreatment. In our modest sample size study, those patients undergoing more intensive therapy had a less favorable course.

A multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/- nab-paclitaxel in elderly pancreatic cancer patients (GrantPax).

BACKGROUND: In the group of elderly patients (≥70 years) with metastatic pancreatic ductal adenocarcinoma (mPDAC), it is not known who benefits from intensive 1st line nab-paclitaxel/gemcitabine (nab-p/gem) combination chemotherapy or who would rather suffer from increased toxicity. We aim to determine whether treatment individualization by comprehensive geriatric assessments (CGAs) improves functional outcome of the patients. METHODS/DESIGN: GrantPax is a multicenter, open label phase 4 interventional trial. We use a CGA to stratify elderly patients into three parallel treatment groups (n = 45 per arm): 1) GOGO (nab-p/gem), 2) SLOWGO (gem mono) or 3) FRAIL (best supportive care). After the 1st cycle of chemotherapy (or 4 weeks in FRAIL group) another CGA and safety assessment is performed. CGA-stratified patients may not decline in their CGA performance in response to the first cycle of chemotherapy (primary objective), measured as a loss of 5 points or less in Barthels activities of daily living. Based on the second CGA, patients are re-assigned to their definite treatment arm and undergo further CGAs to monitor the course of treatment. Secondary endpoints include CGA scores during the course of therapy (CGA1-4), response rates, safety and survival rates. DISCUSSION: GrantPax is the first trial implementing a CGA-driven treatment to personalize therapy for elderly patients with pancreatic cancer. This may lead to standardization of therapy decisions for elderly patients and may optimize standard of care for this increasing group of patients. TRIAL REGISTRATION: NCT02812992 , registered 24.06.2016.

Application of proteome analysis to the assessment of prognosis and response prediction in clinical oncology.

In Europe more than 3 million individuals develop a malignancy annually. Despite recent progress in screening, diagnosis and therapy of most cancers, prognosis remains poor and only a minority of patients are cured. This owes to the fact that most cancers are diagnosed in advanced stages and due to the fact that treatment options for most cancers are limited. While there has been a substantial improvement in systemic therapy for many cancers it remains difficult to assess the potential responsiveness of the cancers towards these newly developed drugs, which include small molecules and monoclonal antibodies. Therefore various strategies have been developed in order to assess the prognosis and predict the expected tumor response in order to individualize the treatment, thereby offering the patient a tailored therapy which accounts for the tumor- and patient-specific morphological and molecular characteristics of the disease. This review summarizes recent efforts, challenges and limitations of proteome analysis in the assessment of prognosis and response-prediction in human cancers.

Comparison of two enzyme immunoassays for the assessment of Helicobacter pylori status in stool specimens after eradication therapy.

OBJECTIVES: Assessment of Helicobacter pylori antigen in stool specimens has recently been proposed as a valid method for the noninvasive detection of H. pylori infection, especially as posttreatment control. After the development of an enzyme immunoassay based on polyclonal antibodies (Premier Platinum HpSA) a monoclonally based test has recently been developed (FemtoLab H. pylori). The aim of the present study was to assess the diagnostic accuracy of both tests in adult patients undergoing H. pylori eradication therapy. METHODS: Stool samples were collected and the 13C-urea breath test performed in 148 patients (79 females and 69 males aged 21-75 yr) 4-6 wk after eradication therapy. The FemtoLab H. pylori and Premier Platinum HpSA tests were performed in accordance with the manufacturers' protocols. A receiver operator characteristics analysis was performed to define the optimal cutoff value on the basis of the results of the 13C-urea breath test. RESULTS: H. pylori eradication was successful in 113 of the 148 patients (76%). After adjusting the cutoff, the sensitivity of FemtoLab H. pylori was found to be higher than that of the Premier Platinum HpSA (94.3% vs 80.0%, ns). Specificity, positive predictive value, and negative predictive value of the two tests were comparable (93.8% vs 95.6%, 82.8% vs 85.2%, and 98.1% vs 93.8%, respectively). CONCLUSIONS: The new stool antigen test (FemtoLab H. pylori) is an excellent tool for diagnosing H. pylori infection after eradication therapy, and its accuracy is comparable with that of the Premier Platinum HpSA. Adjustment of the cutoff after H. pylori eradication therapy increases the overall accuracy.