Faculty Bibliography

BACKGROUND:Radiation therapy (RT)-induced cardiotoxicity is among the concerning sequelae of breast cancer (BCA) treatment, particularly in HER2-positive BCA patients who receive anthracyclines and trastuzumab-based therapy. The aim of this study was to assess for early RT-induced changes in echocardiographic and circulating biomarkers of left ventricular (LV) function and evaluate their association with radiation dose to the heart among patients with HER2-positive BCA treated with contemporary RT. METHODS:A total of 47 women with HER2-positive BCA who were treated with an anthracycline, trastuzumab, and RT to the breast and/or chest wall ± regional lymph nodes were included in this study. Two-dimensional echocardiography with speckle-tracking imaging was performed at baseline (prechemotherapy), prior to and after RT (pre-RT and post-RT), and 6 months post-RT. High-sensitivity troponin I (hsTnI) was measured pre-RT and post-RT. Associations between mean heart dose (MHD) and changes in LV function after RT were examined in multivariable linear regression models. RESULTS:The MHD was 1.8 ± 1.5 Gy for patients receiving left-sided RT (n = 26) and 1.1 ± 1.3 Gy for patients receiving right-sided RT (n = 21). Pre-RT, post-RT, and 6-month post-RT echocardiograms were performed at median (interquartile range) of 49 days (27, 77) before and 54 days (25, 78) and 195 days (175, 226) after RT, respectively. Compared with pre-RT, a minimal decrease in LV ejection fraction was observed post-RT (61% ± 7% vs 59% ± 8%; P = .003) without any significant change in global longitudinal, circumferential, or radial strain or diastolic indices at the post-RT timepoint. Median (interquartile range) concentrations of hsTnI decreased from 5.7 pg/mL (3.0, 8.7) pre-RT to 3.7 pg/mL (2.0, 5.9) post-RT. There was no significant change in systolic or diastolic indices of LV function at 6 months post-RT compared with pre-RT. MHD was not associated with changes in echocardiographic parameters of LV function after RT. CONCLUSIONS:Breast RT using contemporary techniques can be delivered without evidence of early subclinical LV dysfunction or injury as measured by echocardiography and hsTnI in patients treated with anthracyclines and trastuzumab. Future studies should focus on identifying alternative biomarkers to elucidate early RT-induced cardiovascular effects and further characterizing long-term cardiovascular outcomes associated with contemporary breast RT.

PURPOSE:The primary goal was to map the anatomic pattern of isolated nodal recurrences (NR) in the supraclavicular (SCV), axillary, and internal mammary nodes (IMNs) in patients with breast cancer treated with curative-intent surgery with or without radiation therapy (RT). Secondary objectives were to assess clinical and pathologic factors associated with patterns of NR and survival rates. METHODS AND MATERIALS:Patients with NR after treatment at a single cancer center during 1998 to 2013 were identified. Patients with prior distant metastases or NR without correlative imaging were excluded. All NRs were overlaid onto representative axial computed tomographic images. Multivariable analysis was performed to identify clinical and pathologic characteristics associated with NR. Kaplan-Meier curves were generated to assess the rate of relapse by nodal region according to pathologic feature or radiation treatment status. RESULTS:The locations of 243 NRs among 153 eligible patients were mapped. The majority of NR occurred in the axilla (42%; 102/243), followed by the IMN (32.5%; 79/243) and the SCV (25.5%; 62/243). Radiation Therapy Oncology Group (RTOG) or European Society for Radiation therapy and Oncology (ESTRO) clinical target volume encompassed 82% (198/243) of NRs. The majority of out-of-field NRs were located in the lateral and posterior SCV region for both RTOG (67%; 30/45) and ESTRO (89%; 49/55) guidelines. The high-risk patients who received regional RT to the SCV relapsed at a similar rate in the medial, but a higher rate in lateral SCV (P = .009), compared with low-risk patients who received no nodal RT. Lymphovascular invasion most strongly associated with IMN NR (P = .001); grade 3 disease highly associated with both IMN (P = .001) and SCV NR (P = .02). The presence of an IMN NR portended for significantly inferior overall survival (OS), compared with an axillary NR, with a 5-year OS of 59% versus 72%, respectively (P = .03). CONCLUSIONS:In this 3-dimensional image-based analysis of NR patterns in breast cancer patients treated with contemporary therapies, the lateral and posterior SCV represented a distinct site of NR that is not routinely included within current breast cancer contouring atlases. Grade 3 breast cancer and LVI were most commonly associated with the development of NR in the SCV. Modifying the CTV to encompass the lateral and posterior SCV in patients with breast cancer with these features might be justified.

BACKGROUND:Postmastectomy proton radiotherapy improves normal tissue sparing in comparison to photon-based approaches. Several studies have reported dosimetry comparison and tolerable acute toxicity profile with limited follow-up. We report our institutional experience of postmastectomy proton radiation including clinical efficacy and toxicities. METHODS:From December 2013 to February 2015, 42 consecutive patients who received mastectomy for non-metastatic breast cancer were treated with adjuvant chest wall and regional nodal proton therapy at a single proton center. 3D conformal uniform scanning with en face matching fields was used. RESULTS:The median follow-up among patients was 35 months (range 1-55 months). There was one local failure, zero regional nodal failure, and six distant failures. The 3-year rate of locoregional disease-free survival was 96.3%, metastasis-free survival was 84.1%, and overall survival was 97.2%. The only local failure event occurred on the chest wall within the radiation field, approximately 2.5 years after the completion of radiation. Skin dermatitis, fatigue, and esophagitis were the most common acute toxicity. All patients developed grade 1 or 2 acute skin toxicity and there was no grade 3 or 4 acute skin toxicity. Proton radiation is able to achieve excellent target coverage with median PTV V95 over 95% and heart sparing with median mean heart dose less than 1 Gy (RBE). CONCLUSION:With close to three years of median follow-up, post-mastectomy proton radiation has shown excellent locoregional control rates and favorable toxicity profile. Long-term adverse effect of heart-sparing radiation will require longer follow-up time and randomized clinical trials.

PURPOSE/OBJECTIVE:Recurrent meningiomas remain therapeutically challenging, often progressive despite multimodality salvage. There are limited data guiding reirradiation (reRT), and proton beam radiation therapy (PBRT) offers a potential advantage owing to lower integral brain dose. PATIENTS AND METHODS/METHODS:We retrospectively conducted a review of 16 patients who received PBRT reRT for recurrent meningiomas. Kaplan-Meier and proportional hazards were used to determine post-PBRT progression-free survival (PFS) and overall survival (OS) and to evaluate clinical predictors. RESULTS: = .049). Overall late grade 3+ toxicity rate was 31%. Two patients (13%) developed radionecrosis at 6 and 16 months after PBRT; only 1 was symptomatic. CONCLUSIONS:This is the first series specifically analyzing PBRT alone as a reRT strategy for recurrent meningioma. We report fair intracranial control with low rates of radionecrosis at 1 year after reRT. However, strategies to achieve durable outcomes are needed, particularly for high-grade tumors.

Guidelines on proton craniospinal irradiation (p-CSI) target volume selection in children are lacking. We examined the impact of target volume selection on growth of children receiving p-CSI at a institution. Records of 58 patients who received p-CSI were reviewed. Median age at treatment initiation was 8 years (range, 2 to 18 y). Spinal target volumes included whole vertebral body (WVB) in 67% and partial vertebral body (PVB) in 33%. Height z-scores before and after p-CSI were assessed using Centers for Disease Control and Prevention stature-for-age charts. Maximal Cobb angle and height z-score change were compared for WVB versus PVB p-CSI using a t test. Among 93% of patients with detailed data, median follow-up was 19 months (range, 2 to 58 mo) after radiation therapy initiation. Quantitative growth evaluations were available for 64% of patients. Median change in height z-score was -0.5 (range, -2.1 to +0.7) after treatment, representing a decrease (P<0.001) in age-adjusted height. WVB patients had significantly greater reduction in height z-score versus PVB patients (P=0.004) but no difference in Cobb angle change (P>0.05). Despite reluctance surrounding its use in younger patients, PVB p-CSI was associated with similar spinal curvature and less growth suppression as compared with WVB p-CSI; a trial comparing WVB versus PVB in children may be warranted.

Proton radiotherapy confers significant dosimetric advantages in the treatment of malignancies that arise adjacent to critical radiosensitive structures. To date, these advantages have been most prominent in the treatment of pediatric and central nervous system malignancies, although emerging data support the use of protons among other anatomical sites in which radiotherapy plays an important role. With advances in the overall treatment paradigm for breast cancer, most patients with localized disease now exhibit long-term disease control and, consequently, may manifest the late toxicities of aggressive treatment. As a result, there is increasing emphasis on the mitigation of iatrogenic morbidity, with particular attention to heart and lung exposure in those receiving adjuvant radiotherapy. Indeed, recent landmark analyses have demonstrated an increase in significant cardiac events that is linked directly to low-dose radiation to the heart. Coupled with practice-changing trials that have expanded the indications for comprehensive regional nodal irradiation, there exists significant interest in employing novel technologies to mitigate cardiac dose while improving target volume coverage. Proton radiotherapy enjoys distinct physical advantages over photon-based approaches and, in appropriately selected patients, markedly improves both target coverage and normal tissue sparing. Here, we review the dosimetric evidence that underlies the putative benefits of proton radiotherapy, and further synthesize early clinical evidence that supports the efficacy and feasibility of proton radiation in breast cancer. Landmark, prospective randomized trials are underway and will ultimately define the role for protons in the treatment of this disease.

BACKGROUND:Among all in-breast tumor recurrences (IBTR) following breast-conserving therapy (BCT), some comprise metachronous new primaries (NPs) while others are true recurrences (TRs). Establishing this distinction remains a challenge. METHODS:We studied 3932 women who underwent BCT for stage I-III breast cancer from 1998 to 2008. Of these, 115 (2.9%) had an IBTR. Excluding patients with inoperable/unresectable recurrences or simultaneous distant metastases, 81 patients with isolated IBTR comprised the study population. An IBTR was categorized as an NP rather than a TR if it included an in situ component. The log-rank test and Kaplan-Meier method were used to evaluate disease-free survival (DFS) and overall survival (OS), and univariate and multivariate analyses were performed using Cox proportional hazards regression models. RESULTS:At a median of 64.5 months from IBTR diagnosis, 28 of 81 patients had DFS events. Five-year DFS was 43.1% in the TR group (p = 0.0001) versus 80.3% in the NP group, while 5-year OS was 59.7% in the TR group versus 91.7% among those with NPs (p = 0.0011). On univariate analysis, increasing tumor size, high grade, positive margins, lymphovascular invasion, node involvement, lack of axillary surgery, chemotherapy, radiation therapy, and IBTR type (TR vs. NP) were significantly associated with worse DFS. Controlling for tumor size and margin status, TRs remained significantly associated with lower DFS (hazard ratio 3.717, 95% confidence interval 1.607-8.595, p = 0.002). CONCLUSION/CONCLUSIONS:The presence of an in situ component is associated with prognosis among patients with IBTR following BCT and may be useful in differentiating TRs and NPs.