Statistics Comparing Radiation Therapies
Healthcare Policy, 1(2) : 152-167
Research Papers
Waiting Time for Radiation Therapy in Breast Cancer Patients in Quebec from 1992 to 1998
Bernard Fortin, Mark S. Goldberg, Nancy E. Mayo, Marie-France Valois, Susan C. Scott and James Hanley
Abstract
Background : This study was conducted among surgically treated breast cancer patients in Quebec to determine waiting time between surgery and post-operative radiation therapy and factors influencing it.Methods : Records of fee-for-service claims and hospitalizations were obtained for all women who, between 1992 and 1998, underwent an invasive procedure for non-metastatic breast cancer. Waiting time was defined as the time between either the last surgical procedure or the last cycle of chemotherapy and the initiation of radiation therapy. Hierarchical linear regression models were used to identify predictors of waiting time.
Results : Over seven years, 29,072 episodes of breast cancer treatments were identified, of which 17,684 included radiation therapy. The number of cases increased by 5.5% per year, but concurrent broadening of indications for radiation therapy led to an increase in the number of breast cancer patients receiving radiation therapy of 9% per year. In hierarchical linear modelling, comparing 1998 to 1992, median waiting time increased by 63% (95% confidence interval [CI] 35%-97%) in patients not receiving chemotherapy and by 35% (95% CI 3%-88%) in patients receiving chemotherapy. Other predictors of shorter waiting times were localized cancer stage, breast-conserving surgery, early consultation with a radiation oncologist, having surgery in a centre with a radiation therapy facility, living close to a radiation therapy facility and living in a higher socio-economic area.
Interpretation : Using administrative databases to evaluate waiting times is feasible. Explanations of the increased waiting time include increased demand, insufficient resources and changes in the indications for breast-conserving surgery and radiation therapy.
[To view the French abstract, please scroll down.] During the last 20 years, the management of breast cancer has changed dramatically. With screening, tumours are smaller, and randomized controlled trials have shown equivalence between mastectomy and breast-conserving surgery followed by radiation therapy (Verkonesi et al. 1990; Sarrazin et al. 1989; van Dongen et al. 1992; Blichert-Toft et al. 1992; Jacobson et al. 1995; Fisher et al. 2002). This, combined with the aging of the population (Wiener and Tilly 2002; Gouvernement du Québec 2001), has generated a continually increasing demand for radiation therapy in treating breast cancer. There are concerns that this increasing demand will reduce the availability of radiation treatments (Mackillop et al. 1995; Benk et al. 1998; Mackillop et al. 1994; Mayo et al. 2001).
Increased waiting times may be important, as the local recurrence rate after conservative surgery and radiation therapy appears to be about 5% but is 20% to 50% after conservative surgery alone (Fisher et al. 2002). However, there is no consensus as to the optimal time to offer radiation.
We knew from a recently published study (Mayo et al. 2001) that waiting times for the surgical component of breast cancer treatment were increasing in Quebec. An earlier report from Ontario on wait times for radiotherapy also depicted a situation that was deteriorating over time (Mackillop et al. 1994). In 1991, the median time between the completion of surgery and initiation of post-operative radiation for breast cancer was 57.8 days - an increase of 102.7% compared to 1982. In 1994, the same researchers surveyed major radiation centres in the United States and in Canada (Mackillop et al. 1995). Their study showed that the median waiting time before radiation therapy was 40 days in the United States and 73 days in Canada. A report from a single centre in Quebec in 1992 showed a median waiting time of 68 days (Benk et al. 1998). Some literature from Europe suggests that waiting times are comparable to those seen in the United States, with a Spanish report showing an overall maximum waiting time of only 60 days for all cancer types and centres in that country (Esco et al. 2003).
Because of the concerns about availability of services, we conducted the present study to estimate secular trends in waiting time for radiation therapy after breast cancer surgery and to identify factors that may influence waiting time.
Subjects and Methods
This study was approved by the McGill University Faculty of Medicine Institutional Review Board and by the Commission d'accès à l'information du Québec. It was population based and included all women aged 20 years and over who had an invasive procedure for the diagnosis or treatment of breast cancer in the province of Quebec between 1992 and 1998.We used the database of physician fee-for-service claims maintained by the Régie de l'Assurance Maladie du Québec (RAMQ) to obtain data on diagnostic and surgical procedures related to the breast including chemotherapy, radiotherapy and visits to radio-oncologists. This was possible because all these procedures have specific codes and are performed by specific specialists, namely, surgeons, oncologists and radiation oncologists, who have unique specialty identifiers. The validity of the RAMQ database has been verified and shown to be high in another setting (Tamblyn et al. 2000). Since no radiation therapy facility in Quebec is private and doctors must bill specific procedure codes to the RAMQ in order to get paid, completeness of the data was expected to be high. During the study period, all breast cancer related procedures were performed in day surgery, thus requiring hospitalization. For that reason, the hospital discharge file (MedEcho) was used to capture additional details concerning the treatments and any missing breast cancer episodes. MedEcho is a mandatory database concerning all the procedures performed during hospital stays. For confidentiality reasons, the only personal patient information provided in the dataset from RAMQ was the women's age in 1992, in five-year categories.
We made use of prior (1980-1991) and subsequent (1999) data to avoid truncating episodes that spanned administrative time periods. The 1996 Canadian census database was used to obtain, for each Forward Sorting Area (first three characters of the postal code), the median income (categorized as high if the median income was higher than the 75th percentile), the proportion of households in which one or more persons had completed high school (categorized as "educated" if more than two-thirds of households in the area included at least one person with a high school diploma) and the distance of the patient's residence to the nearest radiation therapy facility (categorized as 0-100 km, 101-400 km and ≥401 km because the often very wide geographical area covered by each Forward Sorting Area did not permit finer stratification). There were 10 radiation therapy centres in Quebec in 1991, and three new centres were opened in the province during the study period.
Since routine mammograms are usually spaced at intervals of at least six months, we considered consecutive surgical procedures to the breast that were separated in time by five months or less to be related to a single breast cancer that was operated on more than once (e.g., the biopsy, the definitive surgery and then a re-excision for positive surgical margins) and not to multiple breast cancers. Any non-surgical treatments delivered later than one year after breast cancer surgery were considered not to be related to that surgical procedure but rather to another cancer event. Topography and morphology codes listed in the hospital discharge database were used to estimate the stage of breast cancer.
Only episodes including breast surgery followed by adjuvant radiotherapy were retained. Excluded were episodes with a diagnosis of disseminated disease, with localized breast cancer occurring after an episode for metastatic cancer and where radiotherapy was begun before surgery.
For patients who did not receive chemotherapy between their surgery and radiation therapy, waiting time was calculated as the number of days between the last surgery in an episode (accounting for possible multiple surgeries) and radiotherapy. For patients who received chemotherapy, the time before the end of the chemotherapy was considered as part of planned treatment and, thus, the waiting time was calculated as the time from the last post-operative chemotherapy code to the initiation of radiation therapy (Figure 1).
[Figure 1]
Statistical methods
Secular trends were analyzed using simple linear regression and logistic regression. To evaluate factors associated with waiting time, hierarchical linear regression models were used. We used the natural logarithm scale for waiting time because it was log-normally distributed. We used hierarchical models because waiting times may be more similar for patients treated in a given hospital (Bryk and Raudenbush 1992). We used a two-level hierarchical model to try to isolate the effects of individual-level variables on waiting time (e.g., tumour stage, type of surgery) from the variation in waiting times explained by the radiation therapy centres' differing waiting lists. This model allowed each radiation therapy centre to have its own median value for waiting time. The effect of any individual-level variable was then analyzed according to that centre-specific median.All statistical tests were two-sided. The reported confidence intervals (CI) were evaluated at the 95% level, and all covariates were adjusted for the others in the retained model.
Results
Demographic characteristics
Between 1992 and 1998, there were 30,446 episodes of surgically treated breast cancers among 27,734 patients. Of these, 1,374 episodes were metastatic, thus leaving 29,072 cancer episodes for analysis.
[Table 1]
[Table 2]
Table 1 shows that the distributions of age and stage of breast
cancer were fairly stable during the study period. Apparent changes
in the age distribution over time are explained by the fact that
age was provided in the database as the patient's five-year age
category in 1992 rather than when she was diagnosed. Table 2 shows
that there was a statistically significant average increase in the
number of breast cancer cases (5.5% per year, 95% CI 3.7%-7.4%), in
the proportion of patients treated with breast-conserving surgery
(average of 0.7% per year, 95% CI 0.3%-1.1%) and in the number of
patients receiving radiation (9% per year; 95% CI 5.7%-12.4%). For
patients treated with breast-conserving surgery, the proportion of
subjects receiving radiation increased from 65% to 77% (annual
increase of 1.8%; 95% CI 1.0%-2.6%). The overall use of
chemotherapy (26% of patients) and radiation therapy for patients
treated with mastectomy (22%) was stable.
Waiting time for radiation therapy
Post-operative radiation therapy was provided in 17,684 (60.8%) of the cancer episodes. Of these, 4,821 contained an indication that chemotherapy was received after surgery and before radiation.
[Figure 2]
Figure 2 shows the median and 95% CI of the waiting time, by year
of treatment, for the group without chemotherapy and for the group
with chemotherapy. For the former group, the median waiting time
was 69 days in 1992 and 88 days (28% longer) in 1998; for the group
receiving post-surgery chemotherapy, the median waiting time was 17
days in 1992 and 22 days (32% higher) in 1998.
[Figure 3]
For patients not receiving chemotherapy, the unadjusted proportion
of patients having to wait more than eight weeks before radiation
therapy increased from 70% in 1992 to 82% in 1998 (Figure 3). If a
12-week cut-off is used, the proportion increased from 36% in 1992
to 57% in 1998.
Tables 3 and 4 show the predictors of waiting time, expressed as the percentage change in the median. The effect estimates of the patient-specific covariates are provided in the first column and the estimated between-centre variation in the patient-specific covariates effects is presented in the second column.
[Table 3]
In the non-chemotherapy group (Table 3), waiting times between 1992
and 1998 increased on average by 63%. There was considerable
variation by radiation centre, explaining 30% of the variability in
waiting times. For example, the 95% confidence interval for the
mean change (63%) between 1992 and 1998 in median wait times across
centres was -11% to +199%. The large variability is due partly to
the opening of radiation centres (with shorter waiting times) in
the later years. Individual-level factors associated with waiting
time were regional cancer spread (9% increase), having had a
mastectomy instead of breast-conserving surgery (25% increase),
living farther than 100 km from a radiation therapy centre (10%
increase), seeing a radiation oncologist before having surgery (30%
decrease), having surgery in a centre where there is a radiotherapy
service (13% decrease) and coming from an area in which the average
level of education is higher (3% decrease). The individual-level
variables in the model explained a small part (15%) of the
variation in waiting times. The only centre-specific variable that
contributed to the model was the proportion of patients from a
high-income area (2% decrease for each 10% increase). The number of
patients that the centres treated per year did not influence
waiting times.
[Table 4]
For the chemotherapy group (Table 4), the radiation therapy centre
at which a given patient was treated explained only 2% of the
variation in waiting times, while the patient-level variables
explained 10% of that variation. The association between
individual- level variables and waiting time in this group was
similar in direction to what was found in the non-chemotherapy
group: regional cancer spread (28% increase), having had a
mastectomy instead of breast-conserving surgery (31% increase) and
having surgery in a centre with a radiotherapy service (-18%). A
trend towards longer waiting times was found in the later years
(35% longer in 1998 than in 1992). The parameters estimates in the
chemotherapy group are less stable because the cohort was
smaller.
Discussion
The main findings from this study are that waiting times for receiving radiation therapy after surgery for breast cancer increased over the study period. The increase in the group receiving chemotherapy is disturbing, because there should have been sufficient time to schedule radiotherapy during the planned delay of three to six months.Most of the variation in waiting times cannot be explained by the available data. This result is not surprising given that this study is based on administrative databases that contain very little data on personal characteristics, medical histories and limited contextual variables. This should not, however, affect the validity of the findings. It was troubling to find an increase in waiting time by distance from the nearest radiation therapy centre. This finding may have been due to difficulties in communication between the treating surgeon and the radiation oncologist. Supporting this observation was a favourable effect on waiting time for patients who had surgery in a centre with a radiation therapy facility on site. These centres are located mainly within large tertiary centres. Some possible explanations for this effect include improved communication between specialists, faster access to diagnostic tests and higher volumes of patients treated by these surgeons.
Other factors adversely affecting waiting time were having had a mastectomy and having regional disease spread. The longer waiting time could have been due to longer healing time after a more extensive surgery or to more thorough investigation and treatment for a more severe disease.
In addition, the effect of socio-economic status and education on waiting time, though small, was surprising considering the universal health insurance coverage in the province of Quebec. This finding may reflect an ability of some women to influence more timely treatment.
Some radiation therapy centres performed better than others. Because each hospital designation code was encrypted, it is difficult to explore possible causes such as total radiation therapy workload, staff shortages and case mix. However, it is likely that some of the radiation centres were newly created and thus may not have had the same backlog as the older ones. It also demonstrates that during the study period, patients could have waited less if they had been transferred from centres with long waiting lists to centres with shorter ones.
A strength of this study is that it is population based and that the data are robust: physicians are paid on the basis of services rendered, and completeness and accuracy of reporting have monetary incentives attached. Because of the universality of medicare, very few procedures would have been performed at private clinics and, thus, coverage of the data is close to 100%. The waiting times for radiation therapy reflected in this study are thus a precise depiction of the situation in Quebec between 1992 and 1998.
A limitation of this study is that these results cannot be used to distinguish system delays from patient delays, as our data sources contain only records for procedures performed by physicians. Nevertheless, in an oncology setting, the delay for which the patient is responsible is often only the time from the appearance of symptoms until the first contact with a healthcare professional, as subsequent diagnostic and therapeutic procedures are usually scheduled on behalf of the patient.
There are no data to suggest an optimal waiting time. As treatment decisions involve major life-altering choices for women, an "appropriate" amount of time is required to choose the best treatment approach (Coates 1999), and this may vary considerably among women. On the other hand, women and their families may face considerable anxiety because of delays. What is of more concern is that long waits may also affect recurrence and survival, as suggested by theory and experience with other cancer sites (Robertson et al. 1998; van der Voet et al. 1998; Petereit et al. 1995; Fortin et al. 2002).
There is only one randomized clinical trial (Recht et al. 1996) and few retrospective studies investigating the effects of delays on breast cancer control (Buchholz et al. 1993; Clarke et al. 1985; Nixon et al. 1994; Buzdar et al. 1993; Vujovic et al. 1998; Froud et al. 2000; Slotman et al. 1994; Recht et al. 1991; Hartsell et al. 1995). In the randomized trial, 244 patients with early breast cancer were assigned, after breast-conserving surgery, to receive a 12-week course of chemotherapy given either before or after breast radiotherapy. There was lower overall survival (73% vs. 81%) and a higher incidence of distant metastasis (36% vs. 25%), but a lower rate of local recurrence (5% vs. 14%), in the group receiving radiotherapy early (thus delaying chemotherapy). These observations have led to the practice of prioritizing chemotherapy over radiation therapy for patients who require it.
A pooled analysis of the retrospective studies (Huang et al. 2003) compared local breast cancer recurrence rates for patients treated later than eight weeks to those receiving their post-operative radiation therapy within eight weeks. The pooled odds ratio of recurrence among patients treated later compared to those treated within eight weeks was 1.62 (95% CI 1.21-2.03), representing a 62% higher risk of recurrence among those receiving radiation more than eight weeks after surgery.
The existing data do not show a relationship between local cancer recurrence rates and survival. The usually slow tumour kinetics of breast cancer (which lead to under-detection of late recurrences in studies with short observation periods) and the option to perform a mastectomy in patients with local recurrence after breast-conserving surgery are possible explanations for this lack of obvious relationship between local recurrences and cancer death.
Because waiting time usually reflects accessibility to services, some measures have been implemented in the province since 1998 to address this issue - for example, centralized management of the waiting lists of all radiation therapy centres and transfer of patients to centres with shorter waiting lists, opening of new radiation therapy units and a significant increase in admissions to the radiation oncology residency program and the radiation technologist training programs.
One has to remain conscious, though, of the unrelenting increase in the total number of breast cancer cases over the years, as shown in this study. As a consequence, we believe that the problem of waiting lists must be kept under close scrutiny if we want to maintain the highest standards of cancer treatment for our population, and the available administrative databases provide a tool to do so.
Temps d'attente pour la radiothérapie chez les femmes atteintes de cancer du sein au Québec de 1992 à 1998
Résumé
Contexte: Cette étude a été menée auprès de femmes atteintes du cancer du sein et qui ont reçu un traitement chirurgical au Québec en vue de déterminer le temps d'attente entre la chirurgie et la radiothérapie postchirurgicale, ainsi que les facteurs influençant le temps d'attente.Méthodes: Nous avons obtenu les données sur les demandes de paiement d'honoraires à l'acte et les hospitalisations pour toutes les femmes qui ont subi une intervention chirurgicale invasive pour un cancer du sein sans métastase entre 1992 et 1998. Le temps d'attente a été défini comme étant le délai entre la dernière intervention chirurgicale ou le dernier cycle de chimiothérapie et le début du traitement de radiothérapie. Des modèles de régression linéaire hiérarchique ont été utilisés pour déterminer les facteurs de prédiction du temps d'attente.
Résultats: Sur une période de sept ans, 29,072 épisodes de traitement contre le cancer du sein ont été répertoriés, dont 17,684 comportaient une radiothérapie. Le nombre de cas a augmenté de 5,5 % par an, mais une hausse concomitante des recommandations de traitement de radiothérapie a entraîné une augmentation de 9 % du nombre de femmes atteintes du cancer du sein qui reçoivent un tel traitement. Lorsqu'on compare 1998 à 1992, le temps d'attente moyen a augmenté de 63 % (intervalle de confiance [IC] de 95 % : 35 à 97 %) chez les patientes n'ayant pas besoin de chimiothérapie et de 35 % (IC de 95 % : 3 à 88 %) chez celles qui reçoivent des traitements systémiques. Parmi les autres facteurs permettant de prédire un temps d'attente plus court, citons le cancer localisé, le traitement chirurgical conservateur, la consultation précoce d'un oncoradiologiste, la chirurgie dans un centre offrant des traitements de radiothérapie, le fait de résider à proximité d'un centre de radiothérapie et l'appartenance à un milieu socio-économique plus favorisé.
Interprétation: Il est possible d'utiliser des bases de données administratives pour évaluer le temps d'attente. Parmi les raisons pouvant expliquer l'augmentation du temps d'attente, citons la demande accrue, les ressources insuffisantes et les changements dans les recommandations de traitement chirurgical conservateur et de radiothérapie.
About the Author
Bernard Fortin, MD, FRCPC
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University
Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal
Mark S. Goldberg, PHD
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University
Division of Clinical Epidemiology, McGill University Health Centre
Department of Medicine, McGill University
Department of Oncology, McGill University
Nancy E. Mayo, PHD
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University
Division of Clinical Epidemiology, McGill University Health Centre
Department of Medicine, McGill University
Marie-France Valois, MSC
Department of Medicine, McGill University
Susan C. Scott, MSC
Division of Clinical Epidemiology, McGill University Health Centre
James Hanley, PHD
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University
Division of Clinical Epidemiology, McGill University Health Centre
Department of Medicine, McGill University
Acknowledgment
Correspondence may be directed to: Dr. Bernard Fortin, Dept. of Radiation Oncology, Centre Hospitalier de l'Université de Montréal, 1560 Sherbrooke East, Montréal, QC H2L 4M1.
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Comments
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You must sign in to comment.The goals of radiation treatment are to eliminate or shrink a tumor, to prevent cancer recurrence, or to relieve a patient’s pain or discomfort that is caused by growing tumors, also known as palliative care. To most effectively treat some forms of cancer, radiation therapy is frequently administered as an adjuvant treatment in which it is given in combination with other treatments to enhance the benefit of either or both treatments. Most commonly radiation therapy is paired with surgery and chemotherapy, but is sometimes used with hormone therapy and other treatments.
There are different types of radiation therapy and different ways that it can be delivered. For more information, see the previous Benchmarks article on Radiation Therapy.
Aradhana Kaushal, M.D., is a staff clinician in NCI’s Radiation Oncology Branch and her work focuses on radiation treatment for prostate and pediatric cancers. Benchmarks talked with Dr. Kaushal about radiation therapy and discussed some of the techniques that are being studied at NIH.
What are the main factors that your look at or that help determine the type of radiation treatment/techniques to be used to treat various cancers?
A number of factors must be evaluated when making decisions about radiation treatment. Key factors are how extensive the tumor is and, when treating the primary tumor, whether any draining lymph node [lymph nodes that drain lymph from the area around the tumor] are affected or might be at high enough risk for harboring disease. The location of the tumor is also important. We have to take into consideration any surrounding critical structures, such as major organs, the spinal cord, or normal bowels that may also receive radiation, and monitor the doses of radiation that these structures are getting. The location of the tumor also determines how the fields of radiation are arranged. For example, if the tumor is in the breast or on the arm, we arrange the fields depending upon where the tumor is in relation to the critical structures.
MRI and CT are decade’s old technologies – how are these older techniques being incorporated into newer types of radiation therapy?
When planning treatment for prostate cancer, we use both CT (computed tomography) and MRI (magnetic resonance imaging). Combining the two methods provides a good picture of the area that needs to be treated, as MRI offers very superior visualization of the prostate versus CT scan.
Endorectal coil MRI scan with contrast is being incorporated more into pretreatment decision making to help determine the best therapies for a prostate cancer patient. [For this test, a tube (the endorectal coil) is placed in the rectum, just behind the prostate, to increase the amount of signal received by the MR unit. During the scan, a contrast agent is injected through an intravenous line to brighten the images.] It’s just one of the pieces of the many pieces of information that we use to determine if a patient is a better surgical candidate or a better radiation treatment candidate. With this technique, we look at various sequences to assess a patient’s extent of disease, meaning the extent of the lesions (abnormalities) in the prostate and the risk of lesions in the prostate for being cancerous. However, MRI is still not considered standard in the community for cancer treatment and only some medical centers, like NIH, use it. It is an area of ongoing investigation.
In a low-risk prostate cancer patient treatment plan, we use MRI in the therapeutic setting to look at what we consider lesions in the prostate, to assess their risk, to biopsy them, and to help us guide the dose of radiation to the suspicious nodule in the treatment. Radiologists need specialized training to read the endorectal MRI scan and at this time there are a limited number of trained professionals.
How does functional MRI compare to positron emission tomography (PET) in terms of trying to detect metabolic activity use as a guideline for treatment?
PET is a functional scan, so it’s not used much in prostate cancer treatment, just because of the way prostate cancer behaves. PET is used more in the treatment of other cancers, such as some gynecological malignancies, head and neck cancers, and various types of lymphoma. At NIH, we are working hard on devising prostate cancer-specific functional imaging techniques.
Much of your research focuses on imaging-based radiation treatment approaches. What advantages do adding an imaging component to radiation treatment offer and what are some obstacles that you face with these techniques?
Imaging assists in diagnosing the cancer and in making treatment decisions. When developing a patient’s treatment plan, we often use multiple imaging methods. For example, one of my colleagues treats brain cancer patients, so if he has an MRI scan of the brain, we often use the MRI along with a planning CT scan to visualize where the tumor is located. Likewise for head and neck cancer patients, we often use a PET scan together with our CT planning scan.
In treating patients, imaging helps us guide the radiation. This is important for treating prostate cancer, because these organs are very mobile inside the body. The prostate moves up and down, side to side, and front to back. In daily radiation treatments for prostate cancer patients, image-guided radiation helps locate the prostate and more accurately direct the radiation so that less normal tissue is exposed to the radiation.
There have been a lot of ads on TV/radio lately for Cyberknife–do you have a sense of whether this technology is better than other radiation delivery tools? How does proton beam therapy compare to Cyberknife?
Cyberknife is still a relatively new technology. It gives what we call hypofractionation –this means that a large dose of radiation is given over fewer days, whereas standard radiation involves a smaller dose of radiation administered daily over more days. What makes this technique a cyberknife is the way you can image and sort of have real-time imaging as well as the conformality or the shaping of the radiation, which allows tumors to be treated that are very close to critical structures. A concern with Cyberknife is that we don’t have much long-term follow-up data. When a larger dose of radiation is given on a daily basis, there may be more potential of late-term toxicities; that’s the classic teaching of radiation oncology. But we don’t know if this is true for Cyberknife because it is still new. We don’t have 10 to15 years of follow-up data to see how patients treated with Cyberknife are doing.
Proton beam radiation is a different technology than Cyberknife that allows potentially more shaping of the radiation. The rationale behind using protons is the way protons behave is they fall off at the end of their spectrum very quickly, so that potentially more normal tissue can be spared. This steep fall-off allows the proton beam to be more targeted than with IMRT (intensity-modulated radiation therapy) or other photon-based methods. Whether this actually translates into a benefit, it’s still too early to tell. For prostate cancer, proton therapy is still an area of controversy in the medical field because IMRT for prostate does such a good job of treating the disease.
Brachytherapy is an internal radiation therapy in which the radioactive material sealed in implants such as wires, tubes, or seeds, is placed very close to or inside a tumor. Is this delivery mechanism falling out of favor? How does brachytherapy affect later surgery?
For prostate cancer specifically, brachytherapy is still being used quite a bit in the medical community. I do not do it currently at NIH, but we are going to start a high-dose rate program for brachytherapy in the near future, which is different from seeds. At NIH, brachytherapy is used to treat gynecologic cancers, because it is considered standard of care. However, brachytherapy is not widely used at a lot of facilities to treat other types of cancer, such as sarcomas. Brachytherapy is very involved because the patient is given a high dose of radiation concentrated in a specific area, so it is time intensive on the physician’s part and on the physics planning part. The decision to use prostate brachytherapy versus other therapies is sometimes a personal philosophy/decision. Many times a patient is a great candidate for external beam radiation, brachytherapy, or surgery. In those cases the patient preference makes the decision.
The ideal prostate cancer candidate for brachytherapy is someone who is low risk, meaning a low Gleason score [A system of grading prostate cancer tissue based on how it looks under a microscope and indicate how likely it is that a tumor will spread], low PSA level [prostate-specific antigen which may be higher than normal in the blood of men who have prostate cancer, benign prostatic hyperplasia (BPH), or infection or inflammation of the prostate gland], and someone who does not have a lot of urinary symptoms. Also, someone who has a low AUA (American Urological Association) symptom score [a method to help men determine how bothersome their urinary symptoms are and to check how effective their treatment is]. The ideal candidate is someone who is relatively healthy but can tolerate the risk of anesthesia, has low urinary symptoms to start with and someone who does not want to commit to the eight weeks of external beam radiation treatment.
Once a patient has had definitive radiation treatment, be it external beam or brachytherapy, doing surgery becomes difficult because there is potentially an increased risk of any surgical complications, such as fistula (an opening) of the bladder or the rectum, because the radiation changes the tissues in the area that is treated. In treating prostate cancer, the prostate, the rectum, and the bladder are all exposed to the radiation so surgery is more complicated and it can potentially be fraught with higher complications.
Have any comparative effectiveness studies been conducted that compared surgery, brachytherapy, and external beam radiation?
For low-risk prostate cancer patients, there’s has never been a randomized trial that looks at surgery vs. brachytherapy vs. external beam. There never will be a study comparing all three of these treatments head to head because you can’t randomize patients, and there is so much patient bias and so much physician bias. So we look at the studies that focus on surgery, that focus on external beam, that focus on brachytherapy and long-term local control [absence of progression] and biochemical-free survival [a patient's PSA level does not rise]. Control is usually excellent for someone who is low risk. It’s great for surgery, external beam, or brachytherapy. As a whole, there’s been an over 85 percent cure rate and in some sub-group of patients it actually higher than that.
What are some other novel technology and/or imaging-based approaches to radiation therapy treatment that are currently in development?
In the future, I think there’s going to be more and better daily guided-imaging radiation that’s going to expand to other cancer sites. New approaches to deliver radiation to make it more sophisticated and more conformal, or targeted, will enable us to target the tumor as accurately as possible and to give it a higher dose of radiation, but spare more of the surrounding structures and tissues. Much work is being done in laboratories at many facilities to develop instruments that can target more towards the tumor and at the cellular level. Investigations on agents that are radioprotectant [substances that protect tissues or lessen the effects of radiation] for noncancerous tissues are also underway.
What factors determine whether you are going to treat a prostate cancer patient with radiation or surgery?
Many factors have to be considered when making this decision. Big picture speaking, we classify patients in terms of risk of disease. We group patients by low risk, intermediate risk, and high risk. For prostate cancer, the risk groups are based on Gleason score, PSA level, digital rectal exam to see how bulky the prostate is, and also whether there is any lymph node involvement or disease that has spread elsewhere. Generally, low-risk patients, someone who has a very small, localized prostate tumor, may be a potential candidate for surgery or radiation, but we also look at their urinary function, sexual function before hand, and also other co-morbidities or illnesses they may have.
What would be the ideal surgical patient and the ideal radiation patient?
For prostate cancer, the ideal surgical patient is a gentleman whose has minimal comorbidities that may pose an anesthesia risk, who has a lower PSA level, generally below 10, who has confined disease, such as heart disease or other factors that could make surgery a risk. That being said, there are some intermediate-risk patients who are good surgical candidates. Our practice at NIH, and I think also in general radiation practice, is that if a person is higher risk, higher Gleason score, and higher PSA level, then they be a better potential candidate for radiation and hormones. However, some physicians still operate on these patients, based on individual patient factors.
For other types of cancer, the decision to do radiation treatment or surgery depends on the type of cancer and where it is located in the body. It’s hard to make a blanket statement, because patient preference also is a factor. It’s an individual choice.
Radiation therapy is often given in combination with chemotherapy. Is there any clear consensus on whether radiation should be given before chemotherapy or vice versa or is it something that will continue to be decided on a cancer by cancer or patient by patient basis?
In terms of deciding whether to treat with chemotherapy first, radiation second or vise versa, it is very cancer specific. The decision depends on the site of the disease and the stage of the cancer, so it is hard to make a blanket statement about all types of cancer. For the initial diagnosis of prostate cancer, chemotherapy is generally not a first-line treatment unless someone is involved in a protocol through one of the various cooperative oncology groups [These groups include researchers, cancer centers, and community physicians that work with NCI to design and conduct clinical trials]. For a gentleman who has high-risk prostate cancer, hormonal therapy is often used in conjunction with radiation as a first-line treatment.
One of your two areas of focus is pediatric cancers. How difficult or different is it to treat children with radiation vs. adults? What are the long-term effects on children of radiation therapy vs. chemotherapy?
The patients at Children’s Hospital are referred to NIH through NCI’s Pediatric Oncology Branch, and we work together as a team to give these children radiation treatments. There are many challenges and differences with treating children with radiation treatment as opposed to adults. Many of the children do not understand what is happening to them, so they are not able to cooperate and remain still for the radiation; therefore we have to give them anesthesia. You can tell an adult to stay still, but you can’t tell a 5-year-old child to stay still and to participate in being put into a radiation immobilization mask on a daily basis. They don’t understand and it’s very frightening for them.
Another issue is that tolerance of radiation is not totally understood in children as well as it is in adults. We try to minimize the dose of radiation in all patients, but particularly in children. In adults, most their cells are fully developed, whereas children are still growing and their cells have not had a chance to get to maturity. Radiation is a therapy that can potentially affect the cell development process. For example, in a young patient with brain cancer, their neurons and brain tissue are still maturing. Unfortunately, as young patients grow older they can have more neurocognitive and neuropsychological symptoms related to radiation treatment than an adult patient may have. There can be growth functional abnormalities and hormonal abnormalities. If a young patient is treated in the brain or skull or head, there is a potential risk for change in the way the patient looks, the way the patient grows, the way the patient matures, and performs in school.
The development of a secondary cancer due to radiation therapy is also a concern with pediatric patients. We discuss this with the patient’s parents and the patient if they are old enough to understand. Some of the children that we treat are so young, 4- or 5-years-old, that they have so many years ahead of them to develop secondary cancers that can occur decades into the future. However, someone who is 70, 80, or 90 years old doesn’t have as much time to develop a secondary cancer.
There’s a huge emotional aspect when treating cancer patients in general, but I think it’s much harder on the staff when it’s children. Nevertheless, it is very rewarding and the staff here at the NIH very much value and enjoy treating the children.
Unfortunately only three percent of adults with cancer enroll in clinical trials. Is the enrollment rate any better here?
Clinical trials are a collaborative effort. With our multidisciplinary prostate cancer clinic, I think we have increased enrollment a lot, and I think we have increased our patient satisfaction as well. Patients come in and instead of running from doctor’s office to doctor’s office, they get to see all of their doctors, such as their urologic oncologist, medical oncologist, radiation oncologist, at one time, after we have conferenced together and reviewed their pathology and radiographic studies as a team. I think this increases patient satisfaction and comfort level, and I think we’ve gotten a lot more patients on clinical trials because of it. Also, I can’t emphasize enough the importance of having all the various doctors weigh in on each patient’s case.
To patients considering participating in a clinical trial, I would like to say that clinical trials are a great way to help further cancer treatment knowledge. Clinical trials are generally under great scrutiny, so there’s always someone checking and double checking on the patients. A patient should feel comfortable in enrolling in a cooperative group clinical trial, after careful scrutiny on their part, of course. They should make sure they understand what they are choosing. I can’t emphasize enough the importance of participating in a clinical trial. If people don’t enroll, we aren’t going to make cancer treatment better five to 10 years from now. Treatments are going to stay where they are today.
What makes clinical work at NIH special?
I want people to realize that the research that we do here at the NIH, and at other cancer facilities, is really important. We know how to treat certain types of cancers today and have a good cure rate for some classes of cancer because someone did research on it 20 or 30 years ago. What was experimental at that time is now considered standard of care. Much important work is also being conducted in the research labs. Also, the patient care staff (doctors, nurses, and radiation therapists) are really energetic about their work and invested in the patients’ well-being and improving cancer care–patient satisfaction is extraordinarily high here. NIH is a very special place to work indeed
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Radiation therapy is a type of cancer treatment that uses high-energy beams or particles to kill cancer cells or reduce tumor size. Radiation therapy damages cells by destroying the genetic material that controls how cells grow and divide. . Radiation therapy is mainly used to treat solid tumors.
