Federico Lorenzo1*, Georgina Miralda2, Sergio Aguiar3 and Aldo Quarneti4
1Assistant Professor, Radiation Oncology Department, Udelar
2Resident, Radiation Oncology Department, Udelar
3Associate Professor, Radiation Oncology Department, Udelar
4Chief Professor, Radiation Oncology Department, Udelar
Submission: May 13, 2019; Published: May 28, 2019
*Corresponding Address: Federico Lorenzo, Radiation Oncology Department. “Dr. Manuel Quintela” Clinics Hospital, Faculty of Medicine, University of the Republic (Udelar), Montevideo, Uruguay, South America
How to cite this article:Federico Lorenzo, Georgina Miralda, Sergio Aguiar, Aldo Quarneti. Truths and Myths of Radiotherapy. Canc Therapy & Oncol Int J. 2019; 13(5): 555875. DOI:10.19080/CTOIJ.2019.13.555875
Radiation Oncology is a highly specialized discipline with a constant and vigorous information update. In this study, we addressed 8 questions that may have a controversial response, of interest for both Radiotherapist and related specialties.
Radiation oncology is a highly specialized therapeutic discipline that requires important radiophysical, radiobiological and clinical knowledge. Radiotherapy uses ionizing radiation, mainly X-rays, gamma and accelerated electrons, and its relationship with living matter as therapeutic means. It is a procedure of physical nature, of locoregional action fundamentally. Working day to day in this exciting discipline, we have heard some concepts that can be controversial, in this study we carry out a systematized bibliographic search to answer these questions.
i. It is contraindicated to wash the irradiated skin during Radiotherapy for breast cancer.
ii. A previously irradiated site of head and neck can’t be re-irradiated.
iii. Irradiation at the breast CTV by tangent fields achieves an acceptable coverage of axillary nodal levels I and II.
iv. The “triple plan” treatment and the use of antifungals is effective for the prophylaxis of mucositis in head and neck radiotherapy.
v. Radiotherapy of verrucous carcinoma (Akerman) is contraindicated.
vi. Radiotherapy is a risk factor for the development of second tumors.
vii. Renal carcinoma is “radioresistant”.
viii. The effectiveness of radiotherapy decreases with a hemoglobin lower than 10 g/dl.
A bibliographic search was performed in pubmed using the key words referring to the proposed controversial statements, sorting searches by reference articles, recent studies and clinical trials. All the abstracts of the selected papers were read in a first instance and at last, a second review was made to choose a maximum of five articles per statement
Radiation therapy techniques for breast cancer have evolved over time. These can affect the incidence and severity of skin reactions. Acute radiation reactions occur between the second and fourth week of treatment and may persist for two to four weeks after the end of treatment. Washing the treated skin could play a preventive role by reducing the incidence of wet desquamation, caused by bacterial and fungal growth, which increase the inflammatory response and damage to basal cells .
In a randomized study, Campbell and Illingworth  analyzed two hypotheses for washing deprivation: first, moisteningthe treated skin increased the severity of the acute skin reaction.
Second, they state that it is not the water itself, but the use associated
with soap and friction caused by washing and drying, which
damages the skin. The patients who performed skin wash presented
less pruritus than those who did not wash, with a statistically
significant difference. Another associated sign was erythema,
which was significantly reduced in patients who performed
skin washing. In the wash group, desquamation decreased by the
eighth week of treatment, while those of non-washing continued
to rise. Little difference was found between the washing groups
with water alone and with soap and water; overall, acute skin
reactions were lower in patients who wash the treated skin.
In a study by Roy et al. , 33% of the patients who did not
wash their skin presented wet desquamation, compared to 14%
of those who did. Although the results were not statistically
significant, they showed a tendency to lower toxicity. This may
indicate that there is actually a positive effect, but that it has
not been demonstrated due to the limited number of patients.
Studies have demonstrated that skin washing influences the
acceptance of treatment, and we believe that it should not be
discouraged during radiotherapy treatment in breast cancer.
Until the 1970s, there were no studies about irradiating
previously treated sites of head and neck, since the concept
of “non-re-irradiable” tissues was the premise of those times
due to the concern of possible serious side effects. By the
early 1990s, the first publications with a significant number of
patients began. One of the main challenges in any re-irradiation
plan is the correct selection of patients, with re-staging studies
including PET-CT, and thus achieve a balance between disease
control and adverse effects. In this selection, it is relevant to
consider some factors such as patient’s performance status, GTV,
radiation dose received previously, time elapsed between the
first course of radiotherapy and the new one  De Crevoisier
 re-irradiated 169 patients with head and neck carcinoma at
radical doses, obtaining an average survival of 10 months and a
rate of side effects grade 3 or 4 of 36% and grade 5 of 3%.
More recent studies analyze different types of fractionation,
use of brachytherapy, fractionated stereotactic radiotherapy
plans, obtaining 2-year local control rates of 30-40%. There
have been further studies with new technologies, such as IMRT,
and using different and to pursuit better conformational doses.
Lee, N  re irradiated 105 patients with IMRT technique, with
an average dose of 59.4 Gy, obtaining a global survival rate at
2 years of 37% and a rate of severe late complications of 11%.
Salama et al. , re irradiate 115 patients with a significant
difference in overall survival at 3 years of 3% vs 30% in a dose
cohort of 58 Gy Therefore, it is plausible to irradiate head and
neck tumors, considering a multidisciplinary behavior and
individual characteristics of the patients.
Several factors such as patient´s age, lymph node status,
molecular profile, among others, influence in the decision of
treating axillary territories in an adjuvant treatment for breast
cancer. In some occasions, it is argued to contour only level III,
inferring that levels I and II are covered satisfactorily by tangent
fields. In our review we found several studies that address this
issue, with a heterogeneous coverage of such levels. Belkacemi
et al. , analyzed the coverage by classic tangent fields with
3D conformal radiotherapy in 105 patients, obtaining in level I
a dose range from 1 to 57 Gy, and in level II from 0 to 46 Gy; 95%
of the prescribed dose was received by of 10% of level I and 3%
of level II, increasing this coverage in the 50% isodose curve to
45% and 11% respectively.
Reznick et al.  analyzed a series of 35 patients. The results
obtained suggest that tangential fields designed to treat only the
breast, do not cover adequately the axillary region, therefore,
prophylactic therapy of the axilla cannot be relied upon. Thus,
obtaining a better conformational dose in level II over level I.
Another study included 15 patients with tumours no greater
than 25mm, who underwent conservative surgery and adjuvant
radiotherapy. The average dose at level I was 48.7% with a
range of 5 to 80% . According to the analyzed studies, the
dose coverage at the axillary levels I and II is heterogeneous,
insufficient and therefore not acceptable for adjuvant treatment
at such levels.
Oral mucositis occurs in approximately 20% up to 40% of
patients receiving conventional chemotherapy, and almost all
patients who receive radiation therapy. Typically, it appears at
the second or third week after starting the treatment and may
persist for months . Mucositis can affect the continuity of the
radiotherapy, due to severe pain, which also affects nutritional
intake, oral hygiene and quality of life. It has been demonstrated
that doses as low as 1000-2000 cGy can cause mucositis.
Benzydamine hydrochloride is a topical nonsteroidal agent that
has anti-inflammatory, analgesic/anesthetic, and antimicrobial
effects. There have been various studies that demonstrate a
reduction in the severity of mucositis in patients with head and
neck cancer. Benzydamine mouthwash is well tolerated, and
favorable effects continue even in the seventh week of treatment
when the majority of patients had received the total dose of
more than 60 Gy .
The mucosal barrier injury related to radiation allows
microbial colonization and infection, which in turn leads to
the amplification of tissue injury. The prevention of a candida
infection should reduce the severity of radiation mucositis .The “triple plan” treatment is usually used for the prophylaxis
of mucositis secondary to radiotherapy. This consists of
combining a topical anesthetic (lidocaine), an antihistamine
(diphenhydramine) and an antacid (aluminum or magnesium
hydroxide); accompanied or not by an antifungal agent. Miller
et al. , in a phase III, randomized study, evaluated the
efficacy of mouthwashes with oral doxepin and triple therapy
with diphenhydramine/lidocaine/antacid versus placebo in the
treatment of oral mucositis. Pain related to radiotherapy was
reduced significantly, compared to placebo
The most frequently isolated species from patients during
radiotherapy are Candida albicans and Candida glabrata. Given
the high prevalence of oral fungal infections during the treatment,
mycological examinations are recommended to identify their
species and determine their sensitivity to drugs in order to
prevent complications. Another study evaluated prophylaxis
with fluconazole and its impact on the severity of oral mucositis
during head and neck radiotherapy. There was a significantly
beneficial impact on the incidence of prolonged interruptions of
radiotherapy related to mucositis, grade 3 or 4, and supported
the hypothesis that candidiasis plays an important role in the
severity of radiation mucositis .
According to the MASCC / ISSO guidelines , an evidencebased
recommendation is the use of benzydamine mouthwash
or low-level laser therapy to prevent oral mucositis in patients
with head and neck cancer, receiving a moderate dose radiation
therapy without concomitant chemotherapy. There was no
evidence regarding the use of sucralfate in the prevention or
treatment of mucositis in patients receiving chemo-radiotherapy.
The triple plan showed benefits in pain relief, however there
is no evidence regarding the prevention of mucositis. On the
other hand, there is evidence that the use of fluconazole and
benzydamine can prevent this effect
Verrucous carcinoma is an unusual variant of well
differentiated squamous cell carcinoma, which was first
described in the oral cavity by Lauren Ackerman in 1947. He
noted that this tumor had a distinctive morphological appearance
and a specific clinical behavior, therefore it should be separated
from the other squamous cell carcinomas. Verrucous carcinoma
has a favorable prognosis even with locoregionally advanced
lesions . Three arguments have been exposed in detriment
of radiotherapy: anaplastic transformation, increased incidence
of post-radiotherapy metastasis, and less local control with
radiotherapy vs surgery.
Given the peculiarity and histopathological difficulties in the
diagnosis of this pathology, in our research, we found less than
5 retrospective studies and no prospective clinical trials. These
studies report from 0 to 7% of anaplastic transformation after
radiant treatment, also occurring in patients undergoing surgicaltreatment. No increase in the incidence of post-radiotherapy
metastasis was demonstrated in any of the series reported
[17-19]. Although local control was significantly greater with
surgery than radiotherapy 85% vs 47.7%, surgically rescued
patients have the same local control rate compared with patients
operated on the first instance . Therefore, we can emphasize
that patients suitable for surgical resection with low morbidity,
is a good primary choice. Patients who require surgery with high
impact on morbidity, radiotherapy is a possible option, and in
no case “anaplastic transformation” will affect the therapeutic
Carcinogenesis is one of the most challenging stochastic
effects of radiotherapy. The main risk factors measured in the
studies of second tumors have been age, size of the treatment
field, the radiotherapy technique, and the use of chemotherapy,
among others. It is estimated that cancer survivors have a
14% higher risk of developing a second tumor compared to
the general population. Tumors are considered secondary
when they have the following characteristics: they are caused
by ionizing radiation effects, they appear inside the radiation
field, those histologically different from the primary, they have
a latency period of several years, they do not exist at the time of
initial diagnosis, and that the patient is not a carrier of a cancerprone
A systematic review of clinical and epidemiological studies
measured the dose-volume distribution and second reported
tumors. These happens in approximately 3 to 40% of cancer
survivors, in a period of 10 to 40 years after the diagnosis of the
first tumor. According to the data obtained, they suggest that
the risk of second tumors in organs and tissues adjacent to or
near the target volume, increases with larger fields of irradiation
. In a study with patients who had second tumors, treated
previously with radiotherapy, 50% of them were in the range
of the initial treatment volume, and 10% within the field. There
was an increase in the frequency of tumors within the volume
of low doses of less than 6 Gy. The latency period for the clinical
manifestation of the second tumors was 18 years for low energy
X-rays and 6 years for gamma rays .
The choice of the least toxic radiation modality in children
and adolescents is essential due to their high radio sensitivity
and lower body surface area. A study of pediatric patients with
brain, head and neck tumors, compared the advantages of proton
therapy with respect to the IMRT and VMAT techniques. They
suggest that the advantage of proton therapy is its ability to limit
the exposure of neighboring organs due to the lack of exit dose.
Therefore, the risk of a second malignant disease is lower when
protons are used compared to conventional photon therapy or
IMRT techniques . The evidence shows that radiotherapy
is a risk factor for the development of second tumors. Moderntechniques, including IMRT, SBRT and particle therapies, can
deliver highly conformed dose distributions, allowing dose
escalation to the target volume, while decreasing it to adjacent
normal tissues, thus reducing the subsequent risk of second
The incidence of renal cell carcinoma is 3% of the tumors in
adults. A large percentage of them are diagnosed in locoregionally
advanced stages, given their retroperitoneal location, and usually
for not presenting symptoms until the tumor has a considerable
volume. The lymph node involvement, renal capsule extension,
involvement of the renal vein and inferior venous thrombosis,
are well known as indicators of poor prognosis, especially if
patients present two or more of these factors .
In these patients, therapeutic strategies have been sought
after surgical treatment in order to improve overall and/or
disease-free survival. For that matter, the role of radiotherapy
has been discussed, taking into account the concept of “radio
resistance”. Three prospective studies were carried out between
the 70s and the 80s, in which the results have been unclear,
unfortunately these works used old techniques, extensive
treatment fields and high fractionation [25-27]. In recent
years, several retrospective studies with diverse results were
presented. Tunio et al.  performed a meta-analysis in which
they concluded that post-operative radiotherapy reduces
locoregional failure significantly, without an impact on the rate
of disease-free survival or global survival. Up to date, there is no
clear evidence of the benefit of adjuvant radiotherapy in renal
carcinoma. New randomized clinical trials with new techniques
and modern technologies are required to unveil this question.
Over the years, several studies have shown an association
between the hemoglobin level and the effectiveness of
radiotherapy. The effects of ionizing radiation on tumor cells are
based on the formation of oxygen free radicals that react with
DNA, inducing cell death. It is presumed that hemoglobin supplies
oxygen to tumor cells, therefore, hypoxia is a determining factor
for radio resistance. A radiation dose, approximately twice or
three times higher, is needed to destroy hypoxic cells compared
to well oxygenated cells. A low concentration of hemoglobin
is a predictor for a decrease in local control and survival after
radiotherapy for cancer of the cervix, bladder, lung, and head
and neck .
In a retrospective analysis, the effects of the hemoglobin
level with respect to the tumor response were compared in
patients with cervical cancer, taking values between 10 g/
dl and> 11 g/dl. In the accelerated hyper fractionation group,
patients with Hb> 11 g/dl had a greater complete response,
statistically significant, compared with those with Hb of 10-
10.9 g/dl. There was no significant difference in the groupthat received concurrent chemotherapy and radiotherapy. The
relative benefit of an adequate level of hemoglobin appears to
be much greater for patients treated with exclusive radiotherapy
than for patients treated with concurrent chemoradiotherapy. It
is possible that the radio sensibilization effect of the improved
hemoglobin levels may compensate, to some extent, the non-use
of concurrent chemotherapy .
Another study evaluated the effect of low hemoglobin levels
pre-treatment in locally advanced squamous cell carcinoma of
the head and neck, with complete resection. Hemoglobin levels
of <12 and> 12 g / dl were associated with 3-year survival rates
of 55% and 87%, respectively, and 5-year survival rates of 25%
and 71%, respectively (p <0.001). Therefore, they suggest that
tumor cell oxygenation and the correction of anemia appear to
be important even after the R0 resection .
Lee WR et al. . confirm the importance of the hemoglobin
level in a prospective, randomized trial in patients with advanced
squamous cell carcinoma of the head and neck. Hemoglobin
levels were stratified as normal (> 14.5 g / dl for men,> 13 g
/ dl for women) or anemic (<14.5 g / dl for men, <13 g / dl for
women). Anemic patients according to conventional criteria,
before starting radiotherapy had a reduction of approximately
40% in survival and increased 30% the locoregional failure
compared to similar patients with normal hemoglobin levels.
There is evidence that tumor control is improved with optimal
hemoglobin levels, however, no consensus has been reached
regarding the exact minimum level that should be maintained
during radiotherapy treatment.
Miller RC, Le-Rademacher J, Sio TTW (2016) A phase III, randomized double-blind study of doxepin rinse versus Magic Mouthwash versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy (Alliance A221304). Int J Radiat Oncol Biol Phys 96(5): 938.
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