A Retrospective Study On the Efficacy of Relative Dose Intensities of Non-Hodgkin's Lymphoma Treatments: Response to Chemotherapy and Overall Survival.
Authors: Wang Gary J , Glinert Keren , Henry David H. 
Published: October 2019

Abstract
Abstract 1388
Poster Board I-410

Introduction:
A common problem with chemotherapy treatments is reduced dose-intensities from treatment delays due to chemotherapy induced toxicities. In 2004, Lyman and colleagues assessed the overall incidence of reduced dose-intensities for 4,522 non-Hodgkin's lymphoma (NHL) patients. They determined that 53% of the patients, due to treatment delays of >7 days (24%) or reduced doses of >15% (40%), received a relative dose intensity (RDI) of <85% compared to NCCN standard dosage, with a mean RDI of 80.57% and a median of 86.48% (Lyman et al 2004 J Clin Onc). A similar study conducted by Lepage et al found 28% of 311 lymphoma patients were treated with <70% of the standard NCCN dose. These patients exhibited decreased chemotherapy response rates and shorter 2 year survival rates, with 61% surviving two or more years compared to 72% of patients getting >70% RDI (Lepage et al 1993 Annals Onc). In light of these studies, we conducted a retrospective chart analysis to assess the average RDI for NHL patients treated at our outpatient oncology clinic between 2006 and 2008, and determine if RDIs had a noticeable impact on patient responses to treatment.

Methods:
The primary objective of our chart review was to calculate the delivered dose intensities of chemotherapy for 60 NHL patients, and determine if a higher RDI resulted in better responses to chemotherapy and 2 year survival rates. We included only patients who received the 21-day cycle cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen, Rituximab-CHOP (R-CHOP) regimen, cyclophosphamide, vincristine, prednisone and rituximab (R-CVP) regimen, or the 14-day cycle R-CHOP regimen. Patients received between 3 and 8 cycles of chemotherapy over a period of 2 to 4 months. We calculated RDI by entering the dates of each cycle of chemotherapy, and the dose delivered of each drug in the regimen, into the Nearspace Inc. RDI calculator (http://www.nearspace.com/medical%2Dcalculator/rdi/). Any delays and/or reductions in the dosage (compared to the standard NCCN 21 or 14 day cycle CHOP/CVP regimen dosages) would result in a lower overall RDI.

Results:
Twelve (25%) of the 60 NHL patients received an RDI of less than 85%, and 5 patients (8.3%) received less than 70% of the standard NCCN dose. Nine patients (15%) received dose reductions of >15% and 10 patients (17%) had treatment delays of >7 days. The mean RDI was 91% and the median was 95%. There was minimal difference between the average RDIs for the treating regimens (CHOP = 91%, R-CHOP 14 = 91%, R-CHOP 21 = 91% and R-CVP = 88%). Patients over the age of 65 received an average RDI of 85% whereas patients under the age of 65 received an average RDI of 94%. Stage I patients (n=10, 16.7%) received an average RDI of 95%, stage II patients (n=11, 18.3%) received an average RDI of 90%, stage III patients (n=17, 28.5%) received an average RDI of 92%, and stage IV patients (n=22, 36.5%) received an average RDI of 87%. Forty-seven patients (78.3%) had a complete response to chemotherapy (average RDI = 92%), 4 patients (6.7%) exhibited a partial response (average RDI = 90.75%), 5 patients (8.3%) showed signs of stable disease (average RDI = 80.6%), and 4 patients (6.7%) had progressive disease (average RDI = 91%). The overall 2 year survival rate for all patients was 93.3%: the survival rate of patients with RDIs <85% and patients with RDIs >85% were both 93.3%.

Conclusion:
Both the mean and median RDI we found were higher than those found in the study by Lyman et al (91% and 95% respectively compared to 81% and 86%), and only 25% of patients received <85% RDI compared to 53% of patients in the study by Lyman and colleagues (Lyman et al 2004 J Clin Onc). The average RDI for our 60 patients was higher than that noted in previous studies (91% vs. 80.57% and 79%), and the overall 2 year survival rate was also correspondingly increased (93.3% vs. 61%) (Lepage et al 1993 Annals Onc; Lyman et al 2004 J Clin Onc). Our study is limited by its small sample size, and is inconclusive regarding whether a RDI of above or below the NCCN standard 85% does impact overall survival (both lower and higher RDI groups had a 93.33% survival rate). However we did find that fewer reduced doses and/or delayed treatments does in fact increase overall 2 year survival rates (93% compared to 72%, Lepage et al 1993) and had a positive impact on chemotherapy responses (87% exhibiting a complete response compared to 53%, Lyman et al 2004). Our study highlights the significance of limiting dose delays and reductions in chemotherapy regimens in order to improve patient responses.

Disclosures:
No relevant conflicts of interest to declare.