Amelioration of oral mucositis pain by NASA near-infrared light-emitting diodes in bone marrow transplant patients.

PURPOSE: This study seeks to investigate the use of extra-orally applied near-infrared phototherapy for the reduction of oral pain secondary to chemotherapy- and radiation therapy-induced mucositis in adult and pediatric hematopoietic stem cell transplant (HSCT) patients. METHODS: Eighty HSCT patients were divided into regular (R) and low (L) risk groups, then to experimental (E) and placebo (P) groups, resulting in four groups (ER, EL, PR, PL). Experimental subjects received 670 (± 10) nm gallium-aluminum-arsinide light-emitting diode device for 80 s at ~50 mW/cm(2) energy density and power exposure of 4 J/cm(2). Placebo patients received the same procedures, but with a placebo phototherapy (identical device but <5 mW/cm(2) energy density). Patients received their respective light therapy once per day starting on the day of the HSCT (day 0) and continued through day +14. Blinded evaluators examined the patients three times per week and scored their oral tissues and patient-reported pain assessments at each evaluation utilizing the WHO, NCI-CTCAE, and OMAS scales. RESULTS: Analysis of the mean scores at each observation demonstrate that the extra-oral application of phototherapy resulted in a significant reduction in patient-reported pain between the ER and PR patients (p < 0.05) at day +14 when graded via the WHO criteria. The ER and EL patients were improved in almost all other categories and assessment scales, but the differences were not statistically significant. CONCLUSION: Phototherapy demonstrated a significant reduction in patient-reported pain as measured by the WHO criteria in this patient population included in this study. Improvement trends were noted in most other assessment measurements.

Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.

INTRODUCTION: Cyclophosphamide-based adjuvant chemotherapy is a mainstay of treatment for women with node-positive breast cancer, but is not universally effective in preventing recurrence. Pharmacogenetic variability in drug metabolism is one possible mechanism of treatment failure. We hypothesize that functional single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes (DMEs) that activate (CYPs) or metabolize (GSTs) cyclophosphamide account for some of the observed variability in disease outcomes. METHODS: We performed a retrospective cohort study of 350 women enrolled in a multicenter, randomized, adjuvant breast cancer chemotherapy trial (ECOG-2190/INT-0121). Subjects in this trial received standard-dose cyclophosphamide, doxorubicin and fluorouracil (CAF), followed by either observation or high-dose cyclophosphamide and thiotepa with stem cell rescue. We used bone marrow stem cell-derived genomic DNA from archival specimens to genotype CYP2B6, CYP2C9, CYP2D6, CYP3A4, CYP3A5, GSTM1, GSTT1, and GSTP1. Cox regression models were computed to determine associations between genotypes (individually or in combination) and disease-free survival (DFS) or overall survival (OS), adjusting for confounding clinical variables. RESULTS: In the full multivariable analysis, women with at least one CYP3A4 *1B variant allele had significantly worse DFS than those who were wild-type *1A/*1A (multivariate hazard ratio 2.79; 95% CI 1.52, 5.14). CYP2D6 genotype did not impact this association among patients with estrogen receptor (ER) -positive tumors scheduled to receive tamoxifen. CONCLUSIONS: These data support the hypothesis that genetic variability in cyclophosphamide metabolism independently impacts outcome from adjuvant chemotherapy for breast cancer.

Benchmarks in clinical productivity: a national comprehensive cancer network survey.

PURPOSE: Oncologists in academic cancer centers usually generate professional fees that are insufficient to cover salaries and other expenses, despite significant clinical activity; therefore, supplemental funding is frequently required in order to support competitive levels of physician compensation. Relative value units (RVUs) allow comparisons of productivity across institutions and practice locations and provide a reasonable point of reference on which funding decisions can be based. METHODS: We reviewed the clinical productivity and other characteristics of oncology physicians practicing in 13 major academic cancer institutions with membership or shared membership in the National Comprehensive Cancer Network (NCCN). The objectives of this study were to develop tools that would lead to better-informed decision making regarding practice management and physician deployment in comprehensive cancer centers and to determine benchmarks of productivity using RVUs accrued by physicians at each institution. Three hundred fifty-three individual physician practices across the 13 NCCN institutions in the survey provided data describing adult hematology/medical oncology and bone marrow/stem-cell transplantation programs. Data from the member institutions participating in the survey included all American Medical Association Current Procedural Terminology (CPT®) codes generated (billed) by each physician during each organization's fiscal year 2003 as a measure of actual clinical productivity. Physician characteristic data included specialty, clinical full-time equivalent (CFTE) status, faculty rank, faculty track, number of years of experience, and total salary by funding source. The average adult hematologist/medical oncologist in our sample would produce 3,745 RVUs if he/she worked full-time as a clinician (100% CFTE), compared with 4,506 RVUs for a 100% CFTE transplant oncologist. RESULTS AND CONCLUSION: Our results suggest specific clinical productivity targets for academic oncologists and provide a methodology for analyzing potential factors associated with clinical productivity and developing clinical productivity targets specific for physicians with a mix of research, administrative, teaching, and clinical salary support.

Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer.

BACKGROUND: The prognosis for women with primary breast cancer and 10 or more involved axillary lymph nodes is poor. High-dose chemotherapy with autologous hematopoietic stem-cell transplantation has been reported to be effective in the adjuvant setting for patients at high risk for relapse. METHODS: We randomly assigned 540 female patients with primary breast cancer and at least 10 involved ipsilateral axillary lymph nodes to receive either six cycles of adjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or the same adjuvant chemotherapy followed by high-dose chemotherapy with cyclophosphamide and thiotepa and autologous hematopoietic stem-cell transplantation. RESULTS: Among the 511 eligible patients, there was no significant difference in disease-free survival, overall survival, or the time to recurrence between those who received CAF alone and those who received CAF plus high-dose chemotherapy and stem-cell transplantation. Among 417 patients fulfilling strict eligibility criteria, the time to recurrence was longer for patients who underwent stem-cell transplantation than for those who received CAF alone. In the transplantation group, nine patients died of transplantation-related complications and a myelodysplastic syndrome or acute myeloid leukemia developed in nine. CONCLUSIONS: The addition of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation to six cycles of adjuvant chemotherapy with CAF may reduce the risk of relapse but does not improve the outcome among patients with primary breast cancer and at least 10 involved axillary lymph nodes. Conventional-dose adjuvant chemotherapy remains the standard of care for such patients.