Elizabeth S. Bloom

Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial

IMPORTANCE The most appropriate dose fractionation for whole-breast irradiation (WBI) remains uncertain. OBJECTIVE To assess acute and 6-month toxic effects and quality of life (QOL) with conventionally fractionated WBI (CF-WBI) vs hypofractionated WBI (HF-WBI). DESIGN, SETTING, AND PARTICIPANTS Unblinded randomized trial of CF-WBI (n = 149; 50.00 Gy/25 fractions + boost [10.00-14.00 Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56 Gy/16 fractions + boost [10.00-12.50 Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287 women 40 years or older with stage 0 to II breast cancer for whom WBI without addition of a third field was recommended; 76% of study participants (n = 217) were overweight or obese. Patients were enrolled from February 2011 through February 2014 and observed for a minimum of 6 months. INTERVENTIONS Administration of CF-WBI or HF-WBI. MAIN OUTCOMES AND MEASURES Physician-reported acute and 6-month toxic effects using National Cancer Institute Common Toxicity Criteria, and patient-reported QOL using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B). All analyses were intention to treat, with outcomes compared using the χ2 test, Cochran-Armitage test, and ordinal logistic regression. RESULTS Of 287 participants, 149 were randomized to CF-WBI and 138 to HF-WBI. Treatment arms were well matched for baseline characteristics, including FACT-B total score (HF-WBI, 120.1 vs CF-WBI, 118.8; P = .46) and individual QOL items such as somewhat or more lack of energy (HF-WBI, 38% vs CF-WBI, 39%; P = .86) and somewhat or more trouble meeting family needs (HF-WBI, 10% vs CF-WBI, 14%; P = .54). Maximum physician-reported acute dermatitis (36% vs 69%; P < .001), pruritus (54% vs 81%; P < .001), breast pain (55% vs 74%; P = .001), hyperpigmentation (9% vs 20%; P = .002), and fatigue (9% vs 17%; P = .02) during irradiation were lower in patients randomized to HF-WBI. The rate of overall grade 2 or higher acute toxic effects was less with HF-WBI than with CF-WBI (47% vs 78%; P < .001). Six months after irradiation, physicians reported less fatigue in patients randomized to HF-WBI (0% vs 6%; P = .01), and patients randomized to HF-WBI reported less lack of energy (23% vs 39%; P < .001) and less trouble meeting family needs (3% vs 9%; P = .01). Multivariable regression confirmed the superiority of HF-WBI in terms of patient-reported lack of energy (odds ratio [OR], 0.39; 95% CI, 0.24-0.63) and trouble meeting family needs (OR, 0.34; 95% CI, 0.16-0.75). CONCLUSIONS AND RELEVANCE Treatment with HF-WBI appears to yield lower rates of acute toxic effects than CF-WBI as well as less fatigue and less trouble meeting family needs 6 months after completing radiation therapy. These findings should be communicated to patients as part of shared decision making. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01266642.

Accelerated partial breast irradiation using the strut-adjusted volume implant single-entry hybrid catheter in brachytherapy for breast cancer in the setting of breast augmentation

PURPOSE Accelerated partial breast irradiation (APBI) has gained popularity as an alternative to adjuvant whole breast irradiation; however, owing to limitations of delivery devices for brachytherapy, APBI has not been a suitable option for all the patients. This report evaluates APBI using the strut-adjusted volume implant (SAVI) single-entry catheter to deliver brachytherapy for breast cancer in the setting of an augmented breast. METHODS AND MATERIALS The patient previously had placed bilateral subpectoral saline implants; stereotactic core biopsy revealed estrogen receptor- and progesterone receptor-positive ductal carcinoma in situ of intermediate nuclear grade. The patient underwent needle-localized segmental mastectomy of her left breast; pathologic specimen revealed no residual malignancy. An SAVI 8-1 device was placed within the segmental resection cavity. Treatment consisted of 3.4 Gy delivered twice a day for 5 days for a total dose of 34 Gy. Treatments were delivered with a high-dose-rate (192)Ir remote afterloader. RESULTS Conformance of the device to the lumpectomy cavity was excellent at 99.2%. Dosimetric values of percentage of the planning target volume for evaluation receiving 90% of the prescribed dose, percentage of the planning target volume for evaluation receiving 95% of the prescribed dose, volume receiving 150% of the prescribed dose, and volume receiving 200% of the prescribed dose were 97.1%, 94.6%, 22.7 cc, and 11.6 cc, respectively. Maximum skin dose was 115% of the prescribed dose. The patient tolerated treatment well with excellent cosmetic results, and limited acute and late toxicity at 8 weeks and 6 months, respectively. CONCLUSIONS Breast augmentation should not be an exclusion criterion for the option of APBI. The SAVI single-entry catheter is another option to successfully complete APBI using brachytherapy for breast cancer in the setting of an augmented breast.

Prospective peer review quality assurance for outpatient radiation therapy

PURPOSE We implemented a peer review program that required presentation of all nonpalliative cases to a weekly peer review conference. The purpose of this review is to document compliance and determine how this program impacted care. METHODS AND MATERIALS A total of 2988 patients were eligible for peer review. Patient data were presented to a group of physicians, physicists, and dosimetrists, and the radiation therapy plan was reviewed. Details of changes made were documented within a quality assurance note dictated after discussion. Changes recommended by the peer review process were categorized as changes to radiation dose, target, or major changes. RESULTS Breast cancer accounted for 47.9% of all cases, followed in frequency by head-and-neck (14.8%), gastrointestinal (9.9%), genitourinary (9.3%), and thoracic (6.7%) malignancies. Of the 2988 eligible patients, 158 (5.3%) were not presented for peer review. The number of missed presentations decreased over time; 2007, 8.2%; 2008, 5.7%; 2009, 3.8%; and 2010, 2.7% (P < .001). The reason for a missed presentation was unknown but varied by disease site and physician. Of the 2830 cases presented for peer review, a change was recommended in 346 cases (12.2%) and categorized as a dose change in 28.3%, a target change in 69.1%, and a major treatment change in 2.6%. When examined by year of treatment the number of changes recommended decreased over time: 2007, 16.5%; 2008, 11.5%; 2009, 12.5%; and 2010, 7.8% (P < .001). The number of changes recommended varied by disease site and physician. The head-and-neck, gynecologic, and gastrointestinal malignancies accounted for the majority of changes made. CONCLUSIONS Compliance with this weekly program was satisfactory and improved over time. The program resulted in decreased treatment plan changes over time reflecting a move toward treatment consensus. We recommend that peer review be considered for patients receiving radiation therapy as it creates a culture where guideline adherence and discussion are part of normal practice.

Longitudinal analysis of patient-reported outcomes and cosmesis in a randomized trial of conventionally fractionated versus hypofractionated whole-breast irradiation.

The authors compared longitudinal patient‐reported outcomes and physician‐rated cosmesis with conventionally fractionated whole‐breast irradiation (CF‐WBI) versus hypofractionated whole‐breast irradiation (HF‐WBI) within the context of a randomized trial.

Shortened radiation therapy schedules for early-stage breast cancer: a review of hypofractionated whole-breast irradiation and accelerated partial breast irradiation.

Breast‐conserving therapy consisting of segmental mastectomy followed by whole‐breast irradiation (WBI) has become widely accepted as an alternative to mastectomy as a treatment for women with early‐stage breast cancer. WBI is typically delivered over the course of 5–6 weeks to the whole breast. Hypofractionated whole‐breast irradiation and accelerated partial breast irradiation have developed as alternative radiation techniques for select patients with favorable early‐stage breast cancer. These radiation regimens allow for greater patient convenience and the potential for decreased health care costs. We review here the scientific rationale behind delivering a shorter course of radiation therapy using these distinct treatment regimens in this setting as well as an overview of the published data and pending trials comparing these alternative treatment regimens to WBI.

A new paradigm for calculating skin dose.

PURPOSE Most institutions model breast epidermis with a surface contour and record the maximum dose on the external surface of the patient. The objective of this study was to compare the external surface contour (ext) model of the skin with our current volumetric model for skin for radiation treatment planning in accelerated partial breast irradiation brachytherapy. METHODS AND MATERIALS A literature search was conducted to identify studies measuring breast epidermal thickness. Clinical plans were performed with a 2-mm contraction of the external surface contour. This 2-mm contraction of the external surface contour was used to approximate breast epidermis thickness. Then, the external surface contour was expanded 5mm outside the external contour of the patient for the second skin model. Maximum doses from the two models were recorded and compared. RESULTS The average breast epidermal thickness from five studies was 1.68mm. Mean percent difference between skin and ext+5mm for balloon plans, strut plans, and all plans was 10.1%, 14.5%, and 12.5%, respectively. Differences in doses between the two skin models were statistically significant (p<0.0001). CONCLUSIONS The volumetric skin model was validated because the average breast epidermal thickness was 1.68mm. The surface model for skin may underestimate the dose delivered to the epidermis by as much as 23.8%. The external surface contour method does not accurately represent the dermatologic skin thickness of the breast as the skin is modeled as a surface rather than a volume. These discrepancies may skew correlations of dose to skin and toxicity determinations.

On the feasibility of treating to a 1.5 cm PTV with a commercial single-entry hybrid applicator in APBI breast brachytherapy

Purpose To evaluate and determine whether 30 patients previously treated with the SAVI™ device could have been treated to a PTV_EVAL created with a 1.5 cm expansion. This determination was based upon dosimetric parameters derived from current recommendations and dose-response data. Material and methods Thirty patients were retrospectively planned with PTV_EVALs generated with a 1.5 cm expansion (PTV_EVAL_1.5). Plans were evaluated based on PTV_EVAL_1.5 coverage (V90, V95, V100), skin and rib maximum doses (0.1 cc maximum dose as a percentage of prescription dose), as well as V150 and V200 for the PTV_EVAL_1.5. The treatment planning goal was to deliver ≥90% of the prescribed dose to ≥90% of the PTV_EVAL_1.5. Skin and rib maximum doses were to be ≤125% of the prescription dose and preferably ≤100% of the prescription dose. V150 and V200 were not allowed to exceed 52.5 cc and 21 cc, respectively. Plans not meeting the above criteria were recomputed with a 1.25 cm expanded PTV_EVAL and re-evaluated. Results Based on the above dose constraints, 30% (9/30) of the patients evaluated could have been treated with a 1.5 cm PTV_EVAL. The breakdown of cases successfully achieving the above dose constraints by applicator was: 0/4 (0%) 6-1, 6/15 (40%) 8-1, and 3/11 (27%) 10-1. For these PTV_EVAL_1.5 plans, median V90% was 90.3%, whereas the maximum skin and rib doses were all less than 115.2% and 117.6%, respectively. The median V150 and V200 volumes were 39.2 cc and 19.3, respectively. The treated PTV_EVAL_1.5 was greater in volume than the PTV_EVAL by 41.7 cc, and 60 cc for the 8-1, and 10-1 applicators, respectively. All remaining plans (17) successfully met the above dose constraints to be treated with a 1.25 cm PTV_EVAL (PTV_EVAL_1.25). For the PTV_EVAL_1.25 plans, V90% was 93.7%, and the maximum skin and rib doses were all less than 109.2% and 102.5%, respectively. The median V150 and V200 volumes were 41.2 cc and 19.3, respectively. The treated PTV_EVAL_1.25 was greater in volume than the PTV_EVAL by 16 cc, 24.9 cc, and 33.5 cc for the 6-1, 8-1 and 10-1 applicators, respectively. Conclusions It is dosimetrically possible to treat beyond the currently advised 1.0 cm expanded PTV_EVAL. Most patients should be able to be treated with a 1.25 cm PTV_EVAL and a select group with a 1.5 cm PTV_EVAL. Applicator size appears to determine the ability to expand to a 1.5 cm PTV_EVAL, as smaller devices were not as propitious in this regard. Further studies may identify additional patient groups that would benefit from this approach.

Lower mean heart dose with deep inspiration breath hold-whole breast irradiation compared with brachytherapy-based accelerated partial breast irradiation for women with left-sided tumors

PURPOSE For left-sided breast cancer, radiation to the heart is a concern. We present a comparison of mean heart and coronary artery biologically effective dose (BED) between accelerated partial breast irradiation (APBI) and whole breast irradiation with deep inspiration breath-hold technique (DIBH-WBI). METHODS AND MATERIALS A total of 100 patients with left-sided, early-stage breast cancer were identified. Fifty underwent single-entry catheter-based APBI and 50 underwent DIBH-WBI. The heart, left anterior descending/interventricular branch, left main, and right coronary artery were delineated. BEDs were calculated from APBI treatment plans (34 Gy in 3.4 Gy twice daily fractions) and for 4 separate plans generated for each DIBH-WBI patient: 50 Gy in 25 fractions (50/25), 50/25 + 10/5 boost, 40/15, and 40/15 + 10/5 boost. RESULTS BED to the heart and coronary vessels were statistically significantly higher with APBI than with any of the DIBH-WBI dose/fractionation schedules. CONCLUSIONS For women with left-sided early-stage breast cancer, DIBH-WBI resulted in statistically significantly lower mean BED to the heart and coronary vessels compared with APBI. This is likely due to increased physical separation between the heart and tumor bed afforded by the DIBH-WBI technique. Long-term assessment of late effects in these tissues will be required to determine whether these differences are clinically significant.

Antiepileptic drug use improves overall survival in breast cancer patients with brain metastases in the setting of whole brain radiotherapy

BACKGROUND AND PURPOSE There is mounting evidence that histone deacetylase (HDAC) inhibitors, e.g. valproic acid (VPA), synergize with radiation to improve outcomes in several cancers. This study was conducted to ascertain whether VPA affected outcomes in breast cancer patients with brain metastases treated with whole brain radiotherapy (WBRT). MATERIALS AND METHODS Records from 253 breast cancer patients with brain metastases treated with WBRT were reviewed. Data regarding use of all antiepileptic drugs (AEDs) were extracted. Kaplan-Meier survival times were calculated using the date of brain involvement as time zero. Cox proportional hazard models were used to determine the association between patient and tumor characteristics and overall survival (OS). RESULTS Median OS for the entire patient cohort was 6 months. Patients receiving VPA (n=20) had a median OS of 11 months versus 5 months for those not receiving VPA (p=0.028). Median OS was 9 months for patients taking any AED (n=101) versus 4 months for those not taking AEDs (p=0.0003). On multivariate analysis both VPA and AED use were associated with improved OS (HR 0.61, p=0.0419; HR 0.59, p=0.0002, respectively). CONCLUSIONS This study suggests the use of AEDs, including VPA, is associated with improved OS in breast cancer patients with brain metastases following WBRT.

Contralateral breast dose from partial breast brachytherapy.

The purpose of this study was to determine the dose to the contralateral breast during accelerated partial breast irradiation (APBI) and to compare it to external beam‐published values. Thermoluminescent dosimeter (TLD) packets were used to measure the dose to the most medial aspect of the contralateral breast during APBI simulation, daily quality assurance (QA), and treatment. All patients in this study were treated with a single‐entry, multicatheter device for 10 fractions to a total dose of 34 Gy. A mark was placed on the patients skin on the medial aspect of the opposite breast. Three TLD packets were taped to this mark during the pretreatment simulation. Simulations consisted of an AP and Lateral scout and a limited axial scan encompassing the lumpectomy cavity (miniscan), if rotation was a concern. After the simulation the TLD packets were removed and the patients were moved to the high‐dose‐rate (HDR) vault where three new TLD packets were taped onto the patients at the skin mark. Treatment was administered with a Nucletron HDR afterloader using Iridium‐192 as the treatment source. Post‐treatment, TLDs were read (along with the simulation and QA TLD and a set of standards exposed to a known dose of 6 MV photons). Measurements indicate an average total dose to the contralateral breast of 70 cGy for outer quadrant implants and 181 cGy for inner quadrant implants. Compared to external beam breast tangents, these results point to less dose being delivered to the contralateral breast when using APBI. PACS number: 87.55.D‐The purpose of this study was to determine the dose to the contralateral breast during accelerated partial breast irradiation (APBI) and to compare it to external beam-published values. Thermoluminescent dosimeter (TLD) packets were used to measure the dose to the most medial aspect of the contralateral breast during APBI simulation, daily quality assurance (QA), and treatment. All patients in this study were treated with a single-entry, multicatheter device for 10 fractions to a total dose of 34 Gy. A mark was placed on the patients skin on the medial aspect of the opposite breast. Three TLD packets were taped to this mark during the pretreatment simulation. Simulations consisted of an AP and Lateral scout and a limited axial scan encompassing the lumpectomy cavity (miniscan), if rotation was a concern. After the simulation the TLD packets were removed and the patients were moved to the high-dose-rate (HDR) vault where three new TLD packets were taped onto the patients at the skin mark. Treatment was administered with a Nucletron HDR afterloader using Iridium-192 as the treatment source. Post-treatment, TLDs were read (along with the simulation and QA TLD and a set of standards exposed to a known dose of 6 MV photons). Measurements indicate an average total dose to the contralateral breast of 70 cGy for outer quadrant implants and 181 cGy for inner quadrant implants. Compared to external beam breast tangents, these results point to less dose being delivered to the contralateral breast when using APBI. PACS number: 87.55.D.