Background. The effects of calorie or sugar control on health and disease has been a hot
topic. While established evidence has proven the health benefits of long-term calorie
restriction, recent preclinical studies show encouraging results of the beneficial effects of
short-term fasting on cancer treatment. In particular, short-term calorie control seems to be
safe and has the potential to increase cancer cell's sensitivity to chemotherapy whereas
protect normal cells from chemotherapy-induced toxicity. More human trials are needed before
translating this intervention into clinical practice.
Study purpose and aims. The overall goal of this study is to examine if nutrition status and
an intervention of sugar and calorie modification will affect patient outcomes in patients
with diffuse large B-Cell lymphoma (DLBCL) receiving R-CHOP. The specific aims are: (1) to
investigate the demographic information and nutrition status (e.g., body mass index, albumin
level, fasting sugar, and hyperglycemic episode) of patients with DLBCL before and during
R-CHOP; (2) to examine the relationships between nutrition status and treatment outcomes of
patients with DLBCL; (3) to evaluate the safety and feasibility of applying the protocol of
calorie modification to patients with DLBCL undergoing R-CHOP; (4) to determine the
short-term impacts of calorie modification on patient outcomes by measuring and comparing the
following parameters between two groups a week after starting each R-CHOP cycle: symptoms,
hematologic parameters (i.e., erythrocyte-, thrombocytes-, and leucocyte counts), metabolic
parameters (i.e., insulin, glucose, insulin growth factor 1), inflammatory response
(C-reactive Protein), and nutrition status (i.e., weight, albumin level, and lean body mass);
(5) to determine how calorie modification affects the therapeutic effects of R-CHOP by (a)
using positron emission tomography and computed tomography (PET/CT scan) at three time
points: before treatment, upon completion of the third cycle, and upon completion of the
whole R-CHOP regimen and (b) following up with the progression-free-survival a year post
treatment.
Methods and sampling. This 5-year research project with three phases will be conducted at
National Taiwan University Hospital. The first phase is a case control, observational study.
By reviewing electronic charts of patients who (1) were newly diagnosed with DLBCL within the
past 5 years, (2) received R-CHOP, (3) were 20-year-old or older at diagnosis, we seek to
examine specific aim 1 and 2. About 500 cases are needed in this phase to achieve 80% power.
The second phase is a pilot study requiring 50 participants to assess feasibility of the
protocol. The third phase is a prospective cohort study in which the safety, feasibility, and
effects of a calorie modification protocol are examined (aim 3, 4, and 5), participants will
be randomized to experimental and comparison group. While comparison group will receive
standard care, experimental group will follow the protocol of calorie modification. The
results of this phase will help finalize the calorie modification protocol and determine the
sample size for the third phase which is a larger randomized controlled trial. For phase two
and three, the inclusion criteria are patients who are (1) diagnosed with advanced DLBCL, (2)
receiving R-CHOP regimen and do not have hypersensitivity reaction, and (3) 20-year-old or
older.
Data analysis. Descriptive statistics, Pearson partial correlation, and multiple linear
regression will be used to analyze relationship among interested variables. Independent-t
test, paired t-test, and Mann-Whitney U test are selected to determine the differences
between groups.
Expecting results. The current study is one among the first few translational research
programs implementing calorie modification strategies in real practice. It is particularly
valuable and innovative in terms of its comprehensive design, extensive scope, and focus of
unexplored population. Results of the current study have a great potential to change current
nutrition recommendations for cancer patients receiving chemotherapy and enhance
evidence-based care.
