Neoplasms

Skin and Connective Tissue Diseases

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Breast Neoplasms

Breast Diseases

Skin Diseases

WBI 5 fractions SIB 5 fractions if needed

WBI 15 fractions SIB 15 fractions if needed

WBI 5 fractions SIB 5 fractions if needed LNI 5 fractions

WBI 15 fractions SIB 15 fractions if needed LNI 15 fractions

TWI 5 fractions SIB 5 fractions if needed LNI 5 fractions

TWI 15 fractions SIB 15 fractions if needed LNI 15 fractions

External beam radiotherapy in 5 fractions of 5,7Gy

WBI 5 fractions

External beam radiotherapy in 15 fractions of 2,67Gy

WBI 15 fractions

External beam radiotherapy in 5 fractions of 5,4Gy

LNI 5 fractions

LNI 15 fractions

Simultaneous boost of 5 x 6,2Gy (6,5Gy in case of involved resection margins) if needed

SIB 5 fractions if needed

Simultaneous boost of 15x3,12Gy (3,33Gy in case of involved resection margins) if needed

SIB 15 fractions if needed

TWI 5 fractions

TWI 15 fractions

Liv Veldeman, M.D., PhD

This study will evaluate the effect of highly accelerated external beam radiotherapy (EBRT) in 5 fractions over 10 days compared to 15 fractions over 3 weeks for early as well as locally-advanced stage breast cancer.

Primary endpoint will be chronic toxicity (breast deformation and retraction). Secondary endpoints are acute toxicity, loco-regional and distant tumor control, patient reported QoL and cosmetic satisfaction. Patients with lymph node irradiation will be closely monitored for radiation induced plexopathy.

Over the age of 65, uptake of adjuvant radiotherapy after surgery for breast cancer declines, even in women with poor prognostic stage or adverse tumor characteristics.

Lowering the number of fractions may reduce reluctancy for radiotherapy in this age group.

In a preceding prospective phase I-II trial, evaluating EBRT over 10 days, results on technical feasibility and acute toxicity were positively evaluated.

However, data on the chronic effects of breast irradiation using high doses per fraction are still sparse.

This trial is developed to compare standard hypo-fractionation in 15 fractions (if needed with simultaneously integrated boost - SIB) with highly accelerated radiotherapy in 5 fractions.

Patients referred for adjuvant radiotherapy after breast conserving surgery will preferably be randomized, depending on the indication, to a study-arm with whole breast irradiation (WBI) +/- SIB or to a study-arm with WBI+/- SIB and lymph node irradiation (LNI).

If patients after breast conserving surgery (BCS) have a strong preference for 5 or 15 fractions, they will be invited to enter the parallel observational arm (patient preference).

Patients referred for adjuvant radiotherapy after mastectomy +/- LNI accepting to participate, can choose a 5 or 15-fraction schedule. No randomization is foreseen in this last observational group.

Outcome of 15 Versus 5 Fractions in Adjuvant Breast Radiotherapy in Women Over 65 Years

A Partially Randomized Patient Preference Trial, Comparing Adjuvant Hypofractionated Radiotherapy in 15 Versus 5 Fractions After Breast Conserving Surgery or Mastectomy for Early or Locally Advanced Breast Cancer in Women Above 65 Years

Patients can accept clinical trial but refuse randomization. In this case they will be allocated to a patient preference study arm, existing also of a 5 or 15 fraction-schedule. The choice of the patient: acceptance or non-acceptance of study, acceptance or non-acceptance of randomization, in case of patient preference arm: acceptance or 5 or 15 fractions.

Measurement of frailty using G8 geriatric screening tool

Cost effectiveness analysis comparing 5 with 15 fractions

Percentage of patients able to perform prone positioning on new breast board: yes or no.

Percentage of patients able to perform breath-hold procedure in prone position: yes or no.

Breast Cancer Conservative treatment.core (BCCT.core) objective measurement

Grade 1: mild; Grade 2: moderate, limiting activity of daily living (ADL); grade 3: severe, limiting ADL

Grade 1: mild, localized topical intervention; Grade 2: intense, oral intervention, skin changes

BREAST-Q questionnaire: Patient reported outcome, evaluating satisfaction with esthetic outcome.

If a screening reveals unilateral pain, loss of function or muscular atrophy in the ipsilateral arm, an EMG will be performed to confirm/exclude RIBP

Ipsilateral or regional breast recurrence

Number of patients alive and without breast cancer recurrence at 2 and 5 years after adjuvant radiotherapy

Number of patients alive, 2 and 5 years after adjuvant radiotherapy

University Hospital, Ghent

WBI: 5 x 5.7Gy Thoracic wall: 5 x 5.7Gy R0 boost: 5 x 6.5Gy R1 boost: 5 x 6.9Gy

Dose-integrated accelerated EBRT in pN0 breast cancer

WBI: 5 x 5.7Gy Thoracic wall: 5 x 5.7Gy R0 boost: 5 x 6.5Gy R1 boost: 5 x 6.9Gy Lymph node region: 5 x 5.4Gy

Dose-integrated accelerated EBRT in pN+ breast cancer

Adjuvant radiotherapy in breast cancer improves local control, also in the elderly. Hormonal therapy in hormone sensitive tumors improves results but can not substitute radiotherapy. Improved local control leads to less breast cancer related morbidity and mortality, also in an older population (Schonberg, JCO, 2011).

Unfortunately, in older patients with lower life expectancy, adjuvant radiotherapy is often omitted. Following reasons are invoked:

* frailty of the patient
* fear for toxicity
* impaired mobility, rendering transportation and positioning more difficult
* dependency for transportation to and from the radiotherapy departement
* negative cost effectiveness ratio, due to high cost (especially for complex techniques and long schedules) and lower benefit (lower life expectancy)

Hypofractionation is feasible without increased toxicity, and combines better local control with patient comfort and lower costs. Further lowering the number of fractions (from 15-21 to 5) will further improve patient comfort, but is challenging when different doses are needed in the same target volume. This problem is addressed using advanced techniques permitting dose-integration.

In the elder with cancer, several unrecognized geriatric problems, including depression and cognitive impairment, can be detected by CGA . Some problems do interact with cancer treatment. In this study screening and assessment is provided to support patients and to develop an inventory of radiotherapy obstacles.

Our study includes breast cancer patients, ≥70 years old, referred for adjuvant radiotherapy after surgical treatment. A schedule of 5 fractions is offered, encompassing different targets of treatment.

Adjuvant radiotherapy in breast cancer improves local control and overall survival, also in the elderly. Hormonal therapy in hormone sensitive tumors improves results but can not substitute radiotherapy (EBCTCG, Lancet, 2011). Improved local control, leads to less breast cancer related morbidity and mortality, also in an older population (Schonberg, JCO, 2011).

Unfortunately, in older patients with lower life expectancy, adjuvant radiotherapy is often perceived as too cumbersome. As a consequence, patients who could have benefit from breast conserving therapy are referred for mastectomy. Even when breast-conserving surgery is chosen, adjuvant radiotherapy is sometimes omitted in frail patients over 70 years fearing the burden of daily transportation to the radiation department. However, omitting radiotherapy results in a higher risk of loco-regional recurrence. It has been shown that older patients have a worse prognosis due to suboptimal treatment, especially in locally advanced breast cancer (Schonberg, JCO, 2011).

Following reasons are invoked by the patients or the care-givers:

* frailty of the patient
* fear for (mostly acute) toxicity
* impaired mobility, rendering transportation and positioning more difficult
* dependency on third parties (family, services) for transportation to and from the radiotherapy departement
* negative cost effectiveness ratio, due to high cost (especially for complex techniques and long schedules) and lower benefit (lower life expectancy)

Hypofractionation and acceleration are proven to be feasible in recent trials (cf. Start Trial, Fast Trial).

Based on these data and in order to overcome above mentioned obstacles for radiotherapy in breast cancer, we start a study with accelerated radiotherapy in women above 70 years old.

As we are experienced in advanced techniques as IMRT, VMAT, simultaneous dose-integration and IGRT, we will use simultaneous dose integrated protocols to permit inclusion of early as well as locally advanced breast cancer.

Integration of doses within one global volume encompasses several advantages:

* number of fractions can be maintained, regardless of the indication
* imprevisible high doses due to overlap of adjacent fields in tangential techniques is avoided
* high dose volume is more adequately limited to the actual region of high risk, as dose difference is smaller.

In order to evaluate the impact of accelerated radiotherapy on the well being of the patient and on the treatment cost, quality of life (QoL) will be measured and a cost-analysis will be performed.

Methodology of research At the radiotherapy intake consultation, patients with age ≥70 years are extensively informed on the advantages and the possible risks of accelerated irradiation. A written documentation of the study is provided to permit consultation of family and general practitioner before consent for participation. Until 1 week before the start of radiotherapy, patients can decide wether or not to participate in this study without impact on the starting day. Inclusion is performed after signing the informed consent.

The aim is to include 70 patients aged ≥ 70 years, who, after signing the informed consent, will be treated with the accelerated schemes over 10 days (5 sessions, every other day). Following doses are prescribed

* Breast: 5x5,7Gy
* R0 boost: 5x6.5Gy
* R1 boost: 5x6.9Gy
* Thoracic wall: 5x5.7Gy
* Lymph nodes: 5x5.4Gy --\> these doses are simultaneously integrated, and regions are prescribed according to our standard protocol .

Positioning of the patient depends on technical possibilities and patient rigidity:

* for breast irradiation without lymph nodes, prone positioning is preferred if feasible, if not the patient is positioned in supine
* for thoracic irradiation with or without lymph node irradiation, patient is always installed in supine position
* for breast + lymph node irradiation, patients are installed in supine position.

End points of our study are acute and chronic toxicity, loco-regional control and QoL.

The study is divided in two different strata (first group without lymph node irradiation, second group with lymph node irradiation) for following reasons:

1. these groups represent different outcomes with lymph node invasion having a negative impact on morbidity, loco-regional control and overall survival
2. a higher frequency of acute moist desquamation might occur in the second group (lymph nodes included) as compared to the first group, due to a larger target volume.
3. the brachial plexus is a special concern, as it lies close or even within the target volume. Therefore we will monitor closely the effects on the brachial plexus for the second group. Nevertheless, as the total dose is lower than with normo-fractionation, the risk for brachial neuropathy is maximally reduced.

Groups

* 40 patients in group 1: irradiation of breast/thoracic wall with or without integrated boost without lymph node irradiation
* 30 patients in group 2: irradiation of breast/thoracic wall with or without integrated boost and with lymph node region irradiation

An application for funding to perform geriatric assessment is introduced. In the elder with cancer, several unrecognized geriatric problems, including depression and cognitive impairment, can be detected bij CGA . Some of these problems even interact with cancer treatment. In this study screening and assessment is provided to develop an inventory of obstacles for undergoing radiotherapy.

When screening scores positive (G8 score ≤ 14/17) geriatric assessment will be performed to evaluate the problems and needs of the patient. Patients will be referred for appropriate treatment and support. As described by Schönberg, treatment in early stage breast cancer might even lead to improved morbidity and mortality when compared to a non-cancer population, due to the 'healthy user' effect, detecting otherwise unrevealed problems. In the scope of this study, this effect can not be evaluated.

Power analysis To estimate the number of patients needed, we applied the Wilson score confidence interval test for binomial proportion, which is a 2-sided exact method for power analysis, using "SAS Power and Sample Size".

Group 1:

To achieve a conditional probability of 87% with an alpha-error of 0,1, a number of 35 patients would be needed. To compensate for drop-outs, we include 40 patients in this study-arm.

Group 2 To achieve a conditional probability of \>95% with an alpha-error of 0,1, a number of 25 patients would be needed. To compensate for drop-outs, we include 30 patients in this study-arm.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Outcome of 15 Versus 5 Fractions in Adjuvant Breast Radiotherapy in Women Over 65 Years	NCT03121248	Breastcancer	WBI 5 fractions WBI 15 fraction... LNI 5 fractions LNI 15 fraction... SIB 5 fractions... SIB 15 fraction... TWI 5 fractions TWI 15 fraction...	65 Years -	University Hospital, Ghent
Highly Accelerated Dose-Integrated Radiotherapy in 5 Fractions in Breast Cancer	NCT04098926	Breast Cancer Radiotherapy	Dose-integrated... Dose-integrated...	70 Years -	University Hospital, Ghent
Outcome of 15 Versus 5 Fractions in Adjuvant Breast Radiotherapy in Women Over 65 Years	NCT03121248	Breastcancer	WBI 5 fractions WBI 15 fraction... LNI 5 fractions LNI 15 fraction... SIB 5 fractions... SIB 15 fraction... TWI 5 fractions TWI 15 fraction...	65 Years -	University Hospital, Ghent
Highly Accelerated Dose-Integrated Radiotherapy in 5 Fractions in Breast Cancer	NCT04098926	Breast Cancer Radiotherapy	Dose-integrated... Dose-integrated...	70 Years -	University Hospital, Ghent

Spots Global Cancer Trial Database for older women

Every month we try and update this database with for older women cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for older women

Every month we try and update this database with for older women cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for older women cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.