Time to loading and locoregional control in perioperative high-dose-rate brachytherapy: The tumor bed effect revisited.
OBJECTIVE
To determine whether the time to loading (TTL) affects locoregional control.


METHODS
Locoregional control status was determined in 301 patients enrolled in several perioperative high-dose-rate brachytherapy (PHDRB) prospective studies conducted at the University of Navarre. The impact of the time elapsed from catheter implantation to the first PHDRB treatment (TTL) was analyzed. Patients treated with PHDRB alone (n = 113), mainly because of prior irradiation, received 32 Gy in eight twice-a-day treatments or 40 Gy in 10 twice-a-day treatments for negative or close/positive margins, respectively. Patients treated with PHDRB + external beam radiation therapy (EBRT) (n = 188) received 16 Gy in four twice-a-day treatments or 24 Gy in six twice-a-day treatments for negative or close/positive margins followed by 45 Gy of EBRT in 25 treatments.


RESULTS
After a median followup of 6.5 years (range, 2-13.6+), 113 patients have failed (37.5%), 65 in the PHDRB-alone group (57.5%) and 48 in the combined PHDRB + EBRT group (25.5%). Patients who started PHDRB before Postoperative Day 5 had a 10-year locoregional control rate of 66.7% and patients who started PHDRB on Postoperative Day 5 or longer had a 10-year locoregional control rate of 51.8% (p = 0.009). Subgroup analysis detected that this difference was only observed in the recurrent cases treated with PHDRB alone (Subset 2; n = 99; p = 0.004). No correlation could be detected between locoregional control rate and TTL in the other patient subsets although a trend toward a decreased locoregional control rate after a longer TTL was observed when they were grouped together (p = 0.089).


CONCLUSIONS
Patients should start PHDRB as soon as possible to maximize locoregional control especially in those recurrent cases treated with PHDRB alone. The time effect in other disease scenarios is less clear.
Department of Radiation Oncology, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain. Electronic address: rmartinezm@unav.es.
Rafael
R
Martínez-Monge
Department of Radiation Oncology, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain.
Germán
G
Valtueña
Department of Medical Oncology, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain.
Marta
M
Santisteban
Department of Radiation Oncology, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain.
Mauricio
M
Cambeiro
Department of Radiation Oncology, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain.
Leyre
L
Arbea
Department of Radiation Oncology, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain.
Luis I
LI
Ramos
Department of Radiation Oncology, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain.
Alicia
A
Olarte
Department of Orthopedic Surgery, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain.
Mikel
M
San-Julián
Department of Otolaryngology, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain.
Juan
J
Alcalde
Department of Oral Surgery, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain.
Luis
L
Naval-Gías
Department of Gynecology, Clínica Universidad de Navarra, University of Navarre, Pamplona, Navarre, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarre, Spain.
Matías
M
Jurado
D001918:Brachytherapy / Q000379:methods*; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D018365:Neoplasm, Residual / Q000532:radiotherapy*; D009369:Neoplasms / Q000628:therapy*; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D017211:Treatment Failure; D059016:Tumor Microenvironment / Q000528:radiation effects*
Locoregional control; Perioperative high-dose-rate brachytherapy; Time to loading