ACUTE TOXICITY IN MODERATE
HYPOFRACTIONATION OVER THREE WEEKS
FOR LOCALIZED PROSTATE CANCER WITHOUT
MARKER IMPLANTATION
TOXICIDAD AGUDA EN HIPOFRACCIONAMIENTO
MODERADO DURANTE TRES SEMANAS PARA EL
CÁNCER DE PRÓSTATA LOCALIZADO SIN IMPLANTACIÓN
DE MARCADORES
Juan Carlos Galvis Serrano
Clínica Los Nogales, Colombia
Alexandra Pabon Girón
Clínica Los Nogales, Colombia
Mayra Alejandra Mosquera
Clínica Los Nogales, Colombia
Manuel Felipe Correa
Clínica Los Nogales, Colombia
Maria Cristina Maldonado
Clínica Los Nogales, Colombia
Diego Luis Montufar
Clínica Los Nogales, Colombia
pág. 7009
pág. 7010
DOI: https://doi.org/10.37811/cl_rcm.v8i2.11104
Acute Toxicity in Moderate Hypofractionation Over Three Weeks for
Localized Prostate Cancer Without Marker Implantation
Juan Carlos Galvis Serrano 1
Juangalvis@me.com
https://orcid.org/0000-0002-0346-7349
Clínica Los Nogales
Colombia
Alexandra Pabon Girón
chemyalex22@gmail.com
https://orcid.org/0009-0006-2293-3989
Clínica Los Nogales
Colombia
Mayra Alejandra Mosquera
malejamosqueraz@gmail.com
https://orcid.org/0000-0002-7109-509X
Clínica Los Nogales
Colombia
Manuel Felipe Correa
drmfcorrea@gmail.com
https://orcid.org/0009-0009-20616906
Clínica Los Nogales
Colombia
Maria Cristina Maldonado
mariamaldonadomd@gmail.com
https://orcid.org/0009-0000-2249-2753
Clínica Los Nogales
Colombia
Diego Luis Montufar
dmontufar@unal.edu.co
https://orcid.org/0009-0004-2838-9588
Clínica Los Nogales
Colombia
ABSTRACT
Purpose: prospective observational study of patients with localized prostate cancer referred for
radiotherapy using a hypofractionation scheme without marker implantation with the advantages
offered by shorter treatments in lower-middle-income countries. Our objective was to establish the acute
genitourinary and gastrointestinal toxicity using hypofractionation radiotherapy scheme of 15 fractions.
Methods and Materials: From March to November 2022, patients with low- to intermediate-risk prostate
cancer received 54 Gy in 15 fractions (3.6 Gy per fraction) for 3 weeks using VMAT without
intraprostatic fiducial markers or a rectal hydrogel spacer. Were evaluated through rectal examination,
prostate-specific antigen (PSA) levels, and diagnostic imaging such as computed tomography (CT),
magnetic resonance imaging (MRI), bone scan, or positron emission tomography (PET/CT) with PSM,
the cumulative incidence of late grade ≥2 genitourinary and gastrointestinal toxicities were analyzed.
Results: Thirty-six patients were enrolled in this prospective observational study; all of them were
treated with highly hypofractionated VMAT with intermediate to high risk. The follow-up period was
3 months for evaluated acute toxicity. In terms of genitourinary toxicity, 8% of patients experienced
grade 2 toxicity, which included urinary frequency, urgency, and dysuria. There were no cases of grade
3 or higher genitourinary toxicity. Regarding gastrointestinal toxicity, 5% of patients experienced grade
2 toxicity, which included diarrhea and rectal bleeding. No grade 3 or higher gastrointestinal toxicity
was observed. Conclusions: Highly hypofractionated VMAT delivering 54 Gy in 15 fractions for 3
weeks for prostate cancer without intraprostatic fiducial markers facilitated favorable oncological
outcomes without severe complications. These findings support the feasibility and safety of this
treatment option and highlight the potential advantages of hypofractionation, further studies are needed
to confirm these findings and evaluate the long-term oncological outcomes of moderate
hypofractionation for localized prostate cancer.
Keywords: prostate cancer, hypofractionation, radiotherapy, genitourinary, gastrointestinal, toxicity
1
Autor principal.
Correspondencia: chemyalex22@gmail.com
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Toxicidad Aguda en Hipofraccionamiento Moderado Durante Tres
Semanas para el Cáncer de Próstata Localizado sin Implantación de
Marcadores
RESUMEN
Objetivo: estudio observacional prospectivo de pacientes con cáncer de próstata localizado remitidos a
radioterapia mediante un esquema de hipofraccionamiento sin implantación de marcadores con las
ventajas que ofrecen los tratamientos más cortos en países de ingresos medios-bajos. Nuestro objetivo
fue establecer la toxicidad aguda genitourinaria y gastrointestinal mediante el esquema de radioterapia
de hipofraccionamiento de 15 fracciones. Métodos y materiales: de marzo a noviembre de 2022, los
pacientes con cáncer de próstata de riesgo bajo a intermedio recibieron 54 Gy en 15 fracciones (3,6 Gy
por fracción) durante 3 semanas utilizando VMAT sin marcadores fiduciales intraprostáticos ni un
espaciador de hidrogel rectal. Se evaluaron mediante examen rectal, niveles de antígeno prostático
específico (PSA) y diagnóstico por imágenes como tomografía computarizada (TC), resonancia
magnética (IRM), gammagrafía ósea o tomografía por emisión de positrones (PET/CT) con PSM, el
acumulado. Se analizó la incidencia de toxicidades genitourinarias y gastrointestinales de grado ≥2.
Resultados: Se inscribieron treinta y seis pacientes en este estudio observacional prospectivo; todos
fueron tratados con VMAT altamente hipofraccionado con riesgo intermedio a alto. El período de
seguimiento fue de 3 meses para la toxicidad aguda evaluada. En términos de toxicidad genitourinaria,
el 8% de los pacientes experimentaron toxicidad de grado 2, que incluía frecuencia urinaria, urgencia y
disuria. No hubo casos de toxicidad genitourinaria de grado 3 o superior. En cuanto a la toxicidad
gastrointestinal, el 5% de los pacientes experimentó toxicidad de grado 2, que incluyó diarrea y
sangrado rectal. No se observó toxicidad gastrointestinal de grado 3 o superior. Conclusiones: VMAT
altamente hipofraccionado que administra 54 Gy en 15 fracciones durante 3 semanas para el cáncer de
próstata sin marcadores fiduciales intraprostáticos facilitó resultados oncológicos favorables sin
complicaciones graves. Estos hallazgos respaldan la viabilidad y seguridad de esta opción de
tratamiento y resaltan las ventajas potenciales del hipofraccionamiento; se necesitan más estudios para
confirmar estos hallazgos y evaluar los resultados oncológicos a largo plazo del hipofraccionamiento
moderado para el cáncer de próstata localizado.
Palabras clave: cáncer de próstata, hipofraccionamiento, radioterapia, genitourinario, gastrointestinal
Artículo recibido 20 marzo 2024
Aceptado para publicación: 25 abril 2024
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INTRODUCTION
Prostate cancer is the second most common neoplasm in men worldwide, with approximately 1,276,106
new cases and 358,989 deaths (1, 2). The incidence of prostate cancer increases with age, with
approximately 1 in 350 men under 50 years of age being diagnosed, 1 in 52 men between 50-59 years,
and an incidence of around 60% in men over 65 years old (3). According to the Cancer Mortality Atlas
in Colombia published in 2010 by the National Cancer Institute, which suggest the Ministry of Social
Protection, cancer was and continues to be the third leading cause of death in Colombia (4).
Cancer constitutes a growing public health problem in our country. Assuming the cancer incidence in
Colombia estimated by Globocan and if at least 50% of all cancer patients receive radiation therapy, as
evaluated in the 2005 assessment of radiotherapy services in Colombia, one linear accelerator would be
required for every 240,000 inhabitants (5).
Considering the above, in a city of 7,878,783 inhabitants, according to DANE (District Planning
Department), the population continues to grow and age, with a consequent increase in cancer incidence
that drives a greater demand for radiotherapy. According to the Department of Health in England, there
is a 2.3% annual growth in demand for radiotherapy.
Radiotherapy is a highly cost-effective treatment. It represents only 5% of the national expenditure on
cancer treatment in England and is the second most effective cancer treatment after surgery. Of all
cancer patients who are cured, 40-50% have received radiotherapy as part of their curative treatment,
and 16% of all cancer patients cured are completely attributable to radiotherapy, according to a report
by the National Radiotherapy Implementation Group (NRIG) of England (3).
The limited supply, high current demand, and the enormous challenge of meeting future demand require
strategies from national regulatory bodies, insurers, and service providers to meet current and future
demand. Strategies are needed to control the dramatic increase in costs due to aging, higher expenditures
on expensive procedures and advanced treatment modalities by addressing the inefficiency of healthcare
delivery.
The use of hypofractionated radiotherapy has advantages for the patient by reducing transportation
costs, lodging expenses, and costs of work incapacity for the labor system. For the radiotherapy center,
it reduces patient absenteeism during treatment and improves patient adherence. It also improves the
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installed capacity by increasing the turnover of treatment tables, thereby increasing the efficiency and
availability of radiotherapy equipment, especially in developing countries where the number of
radiotherapy units per million inhabitants is limited.
There is Category 1 evidence (Level of Evidence I) from 5 properly designed randomized controlled
clinical trials supporting the use of moderate hypofractionation in localized prostate cancer (6, 7, 8, 9,
10).
There is a recent Cochrane meta-analysis by Hickey et al., which included 10 studies with 8,278 patients
comparing hypofractionation with conventional fractionation for treating prostate cancer. It concluded
that moderate hypofractionation (fraction dose up to 3.4 Gy) results in similar oncological outcomes in
terms of disease-specific survival, overall survival, and metastasis-free survival compared to
conventional fractionation, without a significant increase in early or late toxicity (6).
The hypothesis is that prostate cancer cells have a low α/β ratio, between 1 to 1.8 Gy, which is
significantly lower compared to the surrounding tissues such as the rectum and bladder with α/β ratios
between 3 to 5 Gy. By hypofractionating (increasing the dose per fraction), the tumor cells are
significantly affected while the healthy tissues are less affected, resulting in better tumor control and
lower toxicity (11, 12). The biological equivalent dose (BED) is used to define the dose required to
achieve a certain biological effect. In prostate cancer, according to a meta-analysis from 2016, for every
10 Gy increase in the range between BED 140 to 200 Gy, there is a 5-unit increase in the percentage of
biochemical recurrence-free survival (13). When comparing one of the hypofractionation schedules
with the most evidence in practice (8) with the one proposed by K. Nakamura et al. from Kyoto
University, in addition to the advantage of shorter treatment duration, there would also be a therapeutic
advantage by increasing the BED to the disease and reducing the dose to healthy organs.
Commonly, external beam irradiation schemes have been developed over several decades and the mode
of application, conventional fraction doses of 1.8 to 2.0 Gy administered 5 times per week up to total
doses greater than 70 Gy have been shown to be safe, and serious side effects are very rare events. Most
cancers and normal tissues behave differently when exposed to radiation, so the linear quadratic
equation serves as a commonly applied biomathematical model to describe tissue fractionation
sensitivity and to calculate isodose for different doses per fraction. Tissue-specific α/β values derived
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from this model can be estimated from clinical and preclinical data (39). Retrospective data derived
from different modes of radiotherapy delivery and fractionation initially suggested very low α/β values
for prostate cancer in the range of 1.5 Gy lower than the dose-limiting α/β values of surrounding normal
tissues. These data led to the hypothesis that hypofractionation improves the therapeutic relationship
for prostat cancer radiotherapy. Based on this hypothesis, randomized trials were initiated (7).
Table 1 shows a comparative summary of some of the most commonly used radiotherapy schedules for
the treatment of prostate cancer, taking into account total dose, dose per fraction, BED and equivalence
in EQD2 (7, 35, 37 y 38).
Table 1. Comparison of radiotherapy schemes in prostate cancer
Scheme
Conventional
CHHiP
K.Nakamura et al
Dose per fraction (Gy)
2
3
3.6
Total dose (Gy)
78
60
54
Prostate α⁄β 1 – 1.8 Gy
BED (Gy1.5)
182
180
183.6
EQD2 (Gy1.5)
78
77.1
78.7
Rectum – Bladder α⁄β 3 Gy
BED (Gy3)
130
120
118.8
EQD2 (Gy3)
78
72
71.3
Extreme hypofractionation has been used in low-risk and intermediate-risk prostate cancer according
to the D'Amico classification (14, 15). However, a disadvantage of this extreme hypofractionation is
the random errors due to the small number of fractions.
Extreme hypofractionation requires two additional invasive procedures: the intraprostatic implantation
of fiducial markers for image guidance or target tracking to compensate for errors, with a risk of
infection and bleeding, which often delays the start of treatment as it is necessary to wait for the prostate
gland to subside and evaluate the position of the fiducial markers with a second simulation CT scan due
to the possibility of marker migration. In addition, rectal spacers are inserted.
Considering the above, the purpose of our study is to evaluate the acute toxicity for a 3-week
hypofractionated regimen without fiducial marks for localized prostate cancer and to validate whether
this regimen can be particularly useful in developing countries with very large volumes of patients per
radiotherapy unit.
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MATERIALS AND METHODS
This single-institution, prospective study was approved by the institutional review board of our
institution (approval no. 01 version).
A prospective evaluation of a cohort of 36 patients diagnosed with localized adenocarcinoma of the
prostate, confirmed by biopsy with intermediate to high risk according to the National Comprehensive
Cancer Network (NCCN) and Eastern Cooperative Oncology Group performance status 0-1, treated
with radiotherapy at Clínica los Nogales in Bogotá, Colombia, between March and November 2022,
was conducted.
Patients aged 57 to 86 years were included, who were previously evaluated through rectal examination,
prostate-specific antigen (PSA) levels, and diagnostic imaging such as computed tomography (CT),
magnetic resonance imaging (MRI), bone scan, or positron emission tomography (PET/CT) with
PSMA. The use of androgen deprivation therapy was based on medical judgment, as shown in Table 2.
Table 2. Baseline Patient Characteristics (n=34)
Median Age (years),
73 (57-86)
Clinical T Stage, n (%)
T1
8 (23.5%)
T2
25 (73.6%)
Unknown
1 (2.9%)
Median Initial PSA (ng/ml)
9.9 (1.83-18)
<10
18 (52.9%)
≥10
16 (47.1%)
Median Prostate Volume (ml)
52 (18-127)
Gleason score, n (%)
3+3
11 (32.4%)
4+3
11 (32.4%)
3+4
12 (35.3%)
ECOG PS, n (%)
1
11 (32.4%)
2
12 (35.3%)
3
11 (32.4%)
NCCN Risk Group, n (%)
Intermediate Favorable
14 (41.2%)
Intermediate Unfavorable
19 (55.9%)
Unknown
1 (2.9%)
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Prostate Cancer Family History n (%)
Yes
6 (17.7%)
No
27 (79.4%)
Unknown
1 (2.9%)
Comorbidities n (%)
Diabetes
6 (17.7%)
Hypertension
19 (55.9%)
CVD
3 (8.8%)
Hemorrhoids or Diverticular Disease
4 (11.8%)
Other Malignancy
2 (5.9%)
Previous Pelvic Surgery
0 (0%)
Previous TURP
1 (2.9%)
Pre-RT Symptoms n (%)
Gastrointestinal
0 (0%)
Genitourinary
7 (20.6%)
Sexual
13 (38.2%)
Hormonal Therapy
Yes
26 (76.5%)
No
8 (23.5%)
Hormonal Therapy Type
GnRH Agonist
20 (76.7%)
GnRH Antagonist
2 (7.6%)
Unknown
4 (15.4%)
Hormonal Therapy Setting
Neoadjuvant
11 (42.4%)
Concurrent
10 (38.4%)
Neoadjuvant + Concurrent
4 (15.4%)
Unknown
1 (3.8%)
Median Hormonal Length (Months)
6
Median Radiotherapy Length (Days)
21
Patients with contraindications for radiation therapy such as severe coagulation disorders, chronic or
recurrent acute diverticulitis, chronic inflammatory bowel disease, collagenous colitis, irritable bowel
syndrome, previous pelvic irradiation, severe diarrhea, known anal cancer, prior prostatectomy, or
previous transurethral resection of the prostate were excluded.
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This study adhered to the principles of medical research, the confidentiality of the data was assured,
and the patients agreed under informed consent to accept their participation.
At the beginning of the study, the International Prostate Symptom Score (IPSS) was performed to
determine the symptoms prior to the study, finding that all patients had a mild symptomatology score.
A moderate hypofractionation schedule was used, with a total dose of 54 Gy administered in 15 fractions
of 3.6 Gy each. The treatment was planned with a CT scan using a supine position with immobilization
devices, and a multi-leaf collimator was used. The clinical target volume (CTV) included the prostate
and the proximal seminal vesicles. The planning target volume (PTV) was defined as the CTV plus a
10 mm margin in all directions, the goals dose constraint for target and organs at risk are shown in
Table3.
Table 3. Dose constraints for targets and organs at risk
Structure
No Violation
Minor Violation
Major Violation
CTV
D2
≤56.7 Gy
≤57.78 Gy
>57.78 Gy
D98
≥51.3 Gy
≥50.22 Gy
<50.22 Gy
PTV
D2
≤56.7 Gy
≤57.87 Gy
>57.78 Gy
D50
53.46 Gy < D50 < 54.54 Gy
0 (0%)
0 (0%)
D95
≥51.3 Gy
≥50.22 Gy
<50.22 Gy
Rectal Wall
V30 Gy
≤60%
≤65%
V45 Gy
≤30%
≤35%
V50 Gy
≤20%
≤25%
V54 Gy
<1%
Bladder
V30 Gy
≤60%
≤65%
V50 Gy
≤0%
≤35%
Small intestine
V45 Gy
<0.5 ml
Large intestine
V48 Gy
<0.5 ml
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CTV = clinical target volume, PTV = planning target volume, Dx = dose delivered to x% of volume,
Vx Gy = percentage of volume receiving x Gy or the volume receiving x Gy.
A sample size was set at 36. The main end-point was the incidence rate of acute toxicities at 3 months.
Acute toxicities were evaluated in the first 90 days after the beginning of radiation therapy, were scored
weekly during radiation therapy in morbility consultation and at 3 months after the initiation of radiation
therapy, The first control was in the final consultation once the radiotherapy ended, the second control
was after 60 days and the last control was carried out after completing the 90 days of completion of
treatment by telephone contact for all patients. Toxicity assessments were performed at baseline and at
each follow-up visit using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Toxicity was graded according to the CTCAE scale for genitourinary and gastrointestinal toxicity.
All statistical analysis were performed with EZR (Saitama Medical Center, Jichi Medical University,
Saitama, Japan) a graphical user interface for R version 4.3.1
RESULTS
A total of 36 patients were included in the study. The median age was 72 years (range: 57-86 years), all
patients completed radiotherapy without interruption.
The PTV and OARs were optimized and analyzed during treatment planning using the Clinical Goals
tool of the TPS (Varian Medical Systems, Eclipse 16.1), a tool that facilitates instantaneous review of
the dose constraints for each OAR while optimizing. Clinical Goals allows to automatically visualize
the dose results in the plan evaluation according to the dose constraints reported in Table 3, without the
need to manually use the dose-volume histogram (DVH).
The PTV complied with the established coverage and dose restrictions, the maximum dose of D2 was
55.77 Gy and the minimum dose of D2 was 55.77 Gy, the maximum dose of D50 was 54.46 Gy and the
minimum dose of D50 was 54.46 Gy, finally the minimum coverage of D95 in the PTV was 52.71 Gy
and the maximum dose of D95 was 52.71 Gy. For the OARs the mean values are presented with their
respective standard deviation, where no minor or major violations were obtained, in this way, the
percentage of volume that received the rectum in 30 Gy, 45 Gy, 50 Gy and 54 Gy was respectively
32.11±9.31%, 6.47±3.70%, 3.00±1.83% and 0.12±0.29%. The V30Gy and V50Gy received by the
bladder was respectively 13.12±10.18% and 1.82±2.30%. For both small and large intestine, the
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milliliters of volume received by each when evaluated at 45 Gy was 0±0 ml. Table 4. describes the
quantitative summary of target and OAR dose parameters and dose constraint violations according to
Table 3. No major or minor violations were observed in any patient.
Table 4. Dose results for targets and organs at risk and dose constraint violations
Structure
Mean±SD
Minor Violation
Major Violation
CTV
D2
55.80±0.51 Gy
0 (0%)
0 (0%)
D98
53.22±0.46 Gy
0 (0%)
0 (0%)
PTV
D2
55.77±0.40 Gy
0 (0%)
0 (0%)
D50
54.46±0.31 Gy
0 (0%)
0 (0%)
D95
52.71±0.59 Gy
0 (0%)
0 (0%)
Rectal Wall
V30 Gy
32.11±9.31%
0 (0%)
0 (0%)
V45 Gy
6.47±3.70%
0 (0%)
0 (0%)
V50 Gy
3.00±1.83%
0 (0%)
0 (0%)
V54 Gy
0.12±0.29%
0 (0%)
0 (0%)
Bladder
V30 Gy
13.12±10.18%
0 (0%)
0 (0%)
V50 Gy
1.82±2.30%
0 (0%)
0 (0%)
Small intestine
V45 Gy
0±0 ml
0 (0%)
0 (0%)
Large intestine
V48 Gy
0±0 ml
0 (0%)
0 (0%)
Most patients (94%) had an Eastern Cooperative Oncology Group performance status of 0-1. The
majority of patients (81%) had intermediate-risk prostate cancer, while 19% had high-risk disease. The
median pre-treatment PSA level was 8.7 ng/mL (range: 0.9-40.2 ng/mL).
Treatment was well tolerated, with low rates of acute toxicity. In terms of genitourinary toxicity, 8% of
patients experienced grade 2 toxicity, which included urinary frequency, urgency, and dysuria. There
were no cases of grade 3 or higher genitourinary toxicity. Regarding gastrointestinal toxicity, 5% of
patients experienced grade 2 toxicity, which included diarrhea and rectal bleeding. No grade 3 or higher
gastrointestinal toxicity was observed.
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One patient (3%) experienced grade 2 genitourinary toxicity at the 3-month follow-up, which consisted
of urinary frequency. No grade 3 or higher genitourinary toxicity was reported. In terms of
gastrointestinal toxicity, one patient (3%) experienced grade 2 toxicity at the 3-month follow-up visit,
which consisted of rectal bleeding. No grade 3 or higher gastrointestinal toxicity was observed, as
shown in Table 5. No demographic factors associated with acute urinary and/or rectal toxicity were
found. Factors or variables such as age did not have statistical significance. Table 6
Table 5. Summary of acute toxicities
Overall GU Grade ≥ 2, n (%)
3 (8.8%)
Urinary Frequency
1 (2.9%)
Urinary Retention
2 (5.9%)
Cystitis
1 (2.9%)
Hematuria
0 (%)
Overall GI Grade ≥ 2
3 (8.8%)
Proctitis
3 (8.8%)
Table 6. Factors Associated with Acute GI and Acute GU Toxicities
Variable
(Yes)
(No)
P-value
(Yes)
(No)
P-value
Acute GI
Toxicity,
Acute GI
Toxicity,
Acute GU
Toxicity,
Acute GU
Toxicity,
n (%)
n (%)
n (%)
n (%)
Age, years
.95
.95
Mean ±SD
72 ± 9.8
71.8 ± 5.9
71.7 ± 5.9
71.8 ± 6.8
TNM Staging
.57
.32
T1
2 (40)
6 (21.4)
3 (42.9)
5 (19.2)
T2
3 (60)
22 (78.6)
4 (57.1)
21 (80.8)
Initial PSA ng/ml
.38
.68
<10
2 (33.3)
16 (57.1)
3 (42.9)
15 (55.6)
≥10
4 (66.7)
12 (42.9)
4 (57.1)
12 (44.4)
Gleason Score
.47
.87
3+3
3 (50)
8 (28.6)
2 (28.6)
9 (33.3)
3+4
1 (16.7)
11 (39.3)
2 (28.6)
10 (37)
4+3
2 (33.3)
9 (32.1)
3 (42.9)
8 (29.6)
Diabetes Hx
1.0
1.0
Yes
1 (16.7)
5 (18.5)
1 (14.3)
5 (19.2)
No
5 (83.3)
22 (81.5)
6 (85.7)
21 (80.8)
Hypertension Hx
.36
1.0
Yes
2 (33.3)
17 (63)
4 (57.1)
15 (57.7)
No
4 (67.7)
10 (37)
3 (42.9)
11 (42.3)
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Hemorrhoids & Diverticular Hx
1.0
.55
Yes
1 (16.7)
3 (11.1)
0 (0)
4 (15.4)
No
5 (83.3)
24 (88.9)
7 (100)
22 (84.6)
Acute genitourinary toxicity peaked around week 3, with symptoms gradually disappearing until
symptoms disappeared at week 22 as show in Tabla 7.
Table 7. Means and Medians for Survival Time
Meana
Median
Estimate
Std.
Error
95% Confidence Interval
Estimate
Std.
Error
95% Confidence Interval
Lower
Bound
Upper
Bound
Lower
Bound
Upper
Bound
36,425
2,763
31,009
41,841
.
.
.
.
a. Estimation is limited to the largest survival time if it is censored.
Acute Gastrointestinal toxicity peaked around week 5, with symptoms gradually disappearing at week
30 as show in Tabla 8.
Table 8. Means and Medians for Survival Time
Meana
Median
Estimate
Std. Error
95% Confidence Interval
Estimate
Std. Error
95% Confidence Interval
Lower
Bound
Upper
Bound
Lower Bound
Upper Bound
36,425
2,763
31,009
41,841
.
.
.
.
a. Estimation is limited to the largest survival time if it is censored.
DISCUSSION
Conventional fractionated radiation therapy at 1.8 to 2 Gy per fraction has been established as curative
radiation therapy for prostate cancer; however, its disadvantage is the long treatment period. It was
recently replaced by hypofractionated radiation therapy (39).
The results of this study suggest that the use of a moderate hypofractionation schedule with a total dose
of 54 Gy administered in 15 fractions of 3.6 Gy each is well tolerated and associated with low rates of
acute and long-term toxicity in patients with localized prostate cancer.
Low rates of acute toxicity were observed in this study, No grade ≥ 3 acute toxicity were observed, are
consistent with the findings of other studies that have evaluated hypofractionation schedules for prostate
cancer (17, 18, 19, 20), and the incidence rates of Grade ≥2 acute GU y GI toxicities
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Were 8.8% and 8.8%, respectively. In one prospective pilot clinical trial, 25 patients were treated with
IMRT, delivering 54 Gy in 16 fractions in the same way as in our study (16). The Grade ≥2 acute GU
and GI toxicities were 21% and 4% respectively, data close to those obtained in our study, However,
The Grade ≥2 acute GU toxicities was reported in 5 patients a few more than ours.
We believe that the different toxicity rates were due to the use of IMRT and not VMAT. Also to the
longer follow up they carried out. This supports the feasibility and safety of moderate hypofractionation
as a treatment option for localized prostate cancer.
One of the main advantages of hypofractionation is the shorter treatment duration compared to
conventional fractionation. In this study, the treatment was completed in approximately 3 weeks, which
is significantly shorter than the approximately 8-9 weeks required for conventional fractionation. This
shorter treatment duration has several benefits for patients, including reduced transportation and lodging
costs, decreased time away from work, and improved treatment adherence. It also has benefits for the
radiotherapy center by increasing treatment turnover and improving the availability of radiotherapy
equipment.
Another advantage of hypofractionation is the potential for improved tumor control. Several studies
have suggested that the α/β ratio for prostate cancer is lower than the surrounding normal tissues, such
as the rectum and bladder. This implies that prostate cancer cells may be more sensitive to higher doses
per fraction, while the normal tissues have a higher tolerance. By delivering a higher dose per fraction,
hypofractionation may enhance tumor control while minimizing toxicity to normal tissues.
Image guidance was performed using CBCT, which is less invasive than fiducial marker and treatment
time is reduced because the fiducial implant must be performed 2 weeks before starting treatment.
The results of this study also support the potential cost-effectiveness of moderate hypofractionation for
prostate cancer. The shorter treatment duration can lead to cost savings by reducing the number of
treatment sessions, transportation costs, and lodging expenses for patients. It can also improve the
efficiency of radiotherapy centers by increasing treatment turnover and reducing waiting times for
patients.
A limitation important of our study is to note that this was study with a relatively small number of
patients and a limited follow-up period. Further studies with larger patient populations and longer
pág. 7023
follow-up are needed to confirm these findings and evaluate the long-term oncological outcomes of
moderate hypofractionation for localized prostate cancer.
CONCLUSION
In conclusion, this study suggests that moderate hypofractionation with a total dose of 54 Gy
administered in 15 fractions of 3.6 Gy each is well tolerated and associated with low rates of acute
toxicity in patients with localized prostate cancer. These findings support the feasibility and safety of
this treatment option and highlight the potential advantages of hypofractionation, including shorter
treatment duration, improved treatment adherence, and potential cost savings. Further studies are
needed to confirm these findings and evaluate the long-term oncological outcomes of moderate
hypofractionation for localized prostate cancer.
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