Faculty Bibliography

PURPOSE/OBJECTIVE:Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS:We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS:442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS:Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

Purpose: Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. Methods: We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan"“Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). Results: 442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96"“155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good"“excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. Conclusions: Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

PURPOSE/OBJECTIVE:Acute radiation dermatitis (ARD) is common after radiation therapy for breast cancer, with data indicating that ARD may disproportionately affect Black or African American (AA) patients. We evaluated the effect of skin of color (SOC) on physician-reported ARD in patients treated with radiation therapy. METHODS AND MATERIALS/METHODS:We identified patients treated with whole breast or chest wall ± regional nodal irradiation or high tangents using 50 Gy in 25 fractions from 2015 to 2018. Baseline skin pigmentation was assessed using the Fitzpatrick scale (I = light/pale white to VI = black/very dark brown) with SOC defined as Fitzpatrick scale IV to VI. We evaluated associations among SOC, physician-reported ARD, late hyperpigmentation, and use of oral and topical treatments for RD using multivariable models. RESULTS:A total of 325 patients met eligibility, of which 40% had SOC (n = 129). On multivariable analysis, Black/AA race and chest wall irradiation had a lower odds of physician-reported grade 2 or 3 ARD (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.030-0.397; P = .001; OR, 0.377; 95% CI, 0.161-0.883; P = .025), whereas skin bolus (OR, 8.029; 95% CI, 3.655-17.635; P = 0) and planning target volume D0.03cc (OR, 1.001; 95% CI, 1.000-1.001; P = .028) were associated with increased odds. On multivariable analysis, SOC (OR, 3.658; 95% CI, 1.236-10.830; P = .019) and skin bolus (OR, 26.786; 95% CI, 4.235-169.432; P = 0) were associated with increased odds of physician-reported late grade 2 or 3 hyperpigmentation. There was less frequent use of topical steroids to treat ARD and more frequent use of oral analgesics in SOC versus non-SOC patients (43% vs 63%, P < .001; 50% vs 38%, P = .05, respectively). CONCLUSIONS:Black/AA patients exhibited lower odds of physician-reported ARD. However, we found higher odds of late hyperpigmentation in SOC patients, independent of self-reported race. These findings suggest that ARD may be underdiagnosed in SOC when using the physician-rated scale despite this late evidence of radiation-induced skin toxicity.

Women who survived childhood cancers or cancers at a young age are at high risk for breast cancer later in life. The accentuated risk is notable among those treated at a young age with a high radiation dose but also extends to survivors treated with therapies other than or in addition to radiation therapy. The predisposing risk factors are complex. Advances in radiation therapy continue to curtail exposure, yet the risk of a second cancer has no dose threshold and a long latency period, and concurrent use of chemotherapy may have an additive effect on long-term risk of cancer. Early screening with annual mammography and MRI is recommended for chest radiation exposure of 10 Gy or greater, beginning 8 years after treatment or at age 25 years, whichever is later. However, there is a lack of recommendations for those at high risk without a history of radiation therapy. Because mortality after breast cancer among survivors is higher than in women with de novo breast cancer, and because there is a higher incidence of a second asynchronous breast cancer in survivors than that in the general population, regular screening is essential and is expected to improve mortality. However, awareness and continuity of care may be lacking in these young patients and is reflected in their poor screening attendance. The transition of care from childhood to adulthood for survivors requires age-targeted and lifelong strategies of education and risk prevention that are needed to improve long-term outcomes for these patients. ^© RSNA, 2023 See the invited commentary by Chikarmane in this issue. Quiz questions for this article are available through the Online Learning Center.

PURPOSE/OBJECTIVE:Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT. METHODS AND MATERIALS/METHODS:Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). RESULTS:Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. CONCLUSION/CONCLUSIONS:In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.

Background: TAS-102 (trifluridine/tipiracil) is a novel oral antimetabolite for late line metastatic colorectal cancer (CRC) approved in 2018. Many patients are treated early in their course with oxaliplatin (OX), particularly adjuvant, and may benefit from re-treatment. In this trial we combine the typical late line use of TAS with OX (BEV [bevacizumab] added at investigator discretion) with goal of improved response.
Method(s): Eligibility included measurable CRC previously treated with all approved drugs per TAS package insert (irinotecan, oxaliplatin, 5FU, anti-VEGF, anti-EGF) as appropriate, PS = 0-1, labs within usual range, neuropathy < grade 2, ability to take oral meds, appropriate contraception. If no contraindication to BEV, this could be added at patient. TAS was dosed at 35 mg/m2 days 1-5 with OX 85/m2 d1 every 14 days (and BEV 5 mg/kg, if given). All supportive care was allowed including growth factors.
Result(s): 47 patients (pts, median age 55) were enrolled in a Simon mini-max design, including 45% female, 21% black, 11% Asian, 11% Hispanic and 5% mixed. 26 pts received BEV. For the first 40 pts, 385 cycles were given (mean = 7 cycles, median 8) with 18 pts (45%) requiring dose reductions (1 dose reduction = 9 pts, 2 = 6, 3 = 3), and 9 receiving (peg)/filgrastim. Toxicities leading to SAEs included gr 3 heme (2), heart failure, abd pain/n/v (6), sepsis (2), urinary (4); and related gr 3 included one gr 3 vomiting and one gr 3 neutropenia. Independently reviewed RECIST Response (N = 32) included PR 2(6%), SD 23 (72%), PD 7 (22%). Mean TTP was 4.5 m (median 4, range 1 - 18) with 9 (28%) pts more than 6 months.
Conclusion(s): In patients with late-line CRC and candidates for TAS (trifluridine/tipiracil), treatment with TAS plus OX is both well tolerated and active. RR is higher than single agent and 78% (95% CI, 60-91%) of patients had stable disease or response, with 60% receiving 8 or more cycles. Randomized trials comparing to single agent TAS are warranted in this setting

INTRODUCTION/BACKGROUND:The purpose of this study is to systematically review data pertaining to breast cancer and radiation-induced skin reactions in patients with skin of color (SOC), as well as data pertaining to objective measurements of skin pigmentation in the assessment of radiation dermatitis (RD). METHODS AND MATERIALS/METHODS:We conducted a systematic review utilizing MEDLINE electronic databases to identify published studies until August 2022. Key inclusion criteria included studies that described RD in breast cancer with data pertaining to skin of color and/or characterization of pigmentation changes after radiation. RESULTS:We identified 17 prospective cohort studies, 7 cross-sectional studies, 5 retrospective studies and 4 randomized controlled trials. Prospective cohort and retrospective series demonstrate worse RD in African American (AA) patients using subjective physician-graded scales. There is more limited data in patients representing other non-White racial subgroups with SOC. 2 studies utilize patient reported outcomes and 15 studies utilize objective methods to characterize pigmentation change after radiation. There are no prospective and randomized studies that objectively describe pigmentation changes with radiotherapy in SOC. CONCLUSIONS:AA patients appear to have worse RD outcomes, though this is not uniformly observed across all studies. There are no studies that describe objective measures of RD and include baseline skin pigmentation as a variable, limiting the ability to draw uniform conclusions on the rate and impact of RD in SOC. We highlight the importance of objectively characterizing SOC and pigmentation changes before, during and after radiotherapy to understand the incidence and severity of RD in SOC.

PURPOSE/OBJECTIVE:The optimal local therapy of patients with nodal disease in supraclavicular (SCV), internal mammary nodes (IMN) and level III axilla is not well studied. We aimed to evaluate the outcomes of patients with breast cancer and advanced nodal disease that received a nodal boost. METHODS AND MATERIALS/METHODS:This retrospective study included 79 patients with advanced nodal disease who underwent adjuvant radiation with a nodal boost to the SCV, IMNs, and/or axilla. All patients had radiographic changes after systemic therapy concerning for gross nodal disease. Overall survival, disease-free survival (DFS), and local recurrence-free survival were estimated using the Kaplan-Meier method. RESULTS:All patients received an initial 50 Gy to the breast/chest wall and regional nodes, of whom 46.8% received an IMN boost, 38.0% axillary (ax)/SCV boost, and 15.2% both IMN and ax/SCV boost (IMN + ax/SCV). Most patients had hormone receptor positive (74.7%) and human epidermal growth factor receptor 2 negative disease (83.5%). In addition, 12.7% of patients had clinical (c) N2 disease, 21.5% cN3A disease, 51.9% cN3B disease, and 5.1% cN3C disease. Most patients received chemotherapy (97.5%). The median nodal boost dose was 10 Gy (range, 10-20 Gy), with 21.6% of IMN, 16.7% of ax/SCV, and 16.7% of IMN + ax/SCV receiving 14 to 20 Gy. With a median follow up of 30 months, the 3-year local recurrence-free survival, DFS, and overall survival rates were 94.5%, 86.3%, and 93.8%, respectively. Crude rates of failure were 13.9% (10.1% distant failure [DF] alone; 3.8% DF + locoregional failure [LRF]). Rates of failure by boost group were 13.3% for ax/SCV (10.0% DF alone; 3.3% DF + LRF), 5.4% for IMN (2.7% DF alone, 2.7% DF + LRF), and 41.7% for IMN + ax/SCV (33.3% DF, 8.3% DF + LRF). There were no LRFs without DFs. The median time to failure was 22.8 months (interquartile range, 18-34 months). Clinical tumor size and IMN + ax/SCV versus IMN or ax/SCV alone was associated with worse DFS (hazard ratio [HR]: 9.78; 95% confidence interval [CI], 2.07-46.2; P = .004 and HR: 9.49; 95% CI, 2.67-33.7; P = .001, respectively). On multivariate analysis, IMN + ax/SCV versus IMN or ax/SCV alone retained significance (HR: 4.80; 95% CI, 1.27-18.13; P = .02). CONCLUSIONS:In this population of patients with locally advanced breast cancer, the majority of failures were distant with no isolated LRFs. Failures were the highest in the IMN + ax/SCV group (∼40%). Further treatment escalation is necessary for these patients.

Radiotherapy omission is increasingly considered for selected patients with early-stage breast cancer. However, with emerging data on the safety and efficacy of radiotherapy de-escalation with partial breast irradiation and accelerated treatment regimens for low-risk breast cancer, it is necessary to move beyond an all-or-nothing approach. Here, we review existing data for radiotherapy omission, including the use of age, tumor subtype, and multigene profiling assays for selecting low-risk patients for whom omission is a reasonable strategy. We review data for de-escalated radiotherapy, including partial breast irradiation and acceleration of treatment time, emphasizing these regimens' decreasing biological and financial toxicities. Lastly, we review evidence of omission of endocrine therapy. We emphasize ongoing research to define patient selection, treatment delivery, and toxicity outcomes for de-escalated adjuvant therapies better and highlight future directions.

Purpose/Objective(s): Radiation dermatitis (RD) is common after RT for breast cancer with data indicating potentially worse RD in African American (AA) patients (pts). Current measures of RD, such as the CTCAE, do not include hyperpigmentation, which may disproportionately affect how RD is classified and treated in pts with skin of color (SOC). We aim to characterize RD in SOC and identify factors, including baseline skin pigmentation (BSP) that predict RD. Materials/Methods: Pts treated with whole breast (WB) or chest wall (CW) with regional nodal RT or high tangents with 50 Gy in 25 fractions from 2015-2018 were identified. Three dermatologists independently classified BSP using photographs from CT simulation based on the Fitzpatrick scale ([FS], range=I-VI; I=light/pale white to VI=black/ very dark brown). SOC was defined as FS IV-VI. Pt characteristics were investigated for association with interventions to treat RD, clinician-graded acute RD, and late skin toxicity (NCI CTCAE scale) with Chi-squared and logistic regression analyses.
Result(s): 325 pts met eligibility criteria (58 African American [AA], 42 Asian, 151 Caucasian, 77 other). 40% (n=129) had SOC, 60% underwent CW RT, 40% WB RT and 82% had systemic therapy. Pts with SOC were more likely to be Hispanic (14% vs 8% p=0.007), AA (43% vs 1%, p<0.001) and have greater mean BMI (28.0 vs 26.5, p=0.02). Acute grade 2/3 RD was lower in SOC (FS I 60%, FS II 63%, FS III 52%, FS IV 64%, FS V 40%, FS VI 41%; p=0.049). Increased BSP (OR 0.83; p=0.01) and AA pts (OR: 0.22; p<0.001) had lower odds of acute grade 2/3 RD, whereas bolus and dosimetric parameters such as increased PTV volume had increased odds. On multivariable analysis (MVA), AA pts and bolus remained significant (OR: 0.14, p=0.01; OR: 6.63 p<0.001, respectively). Topical steroid use to treat RD was less frequent and oral analgesic use was more frequent in SOC (43% vs 63%, p<0.001; 50% vs 38%, p=0.05, respectively). Pts with increased BSP (OR 0.73, p<0.001), AA race (OR 0.19, p<0.001) and greater BMI had lower use of topical interventions whereas any boost phase, bolus, IMN RT and increased PTV volume had greater use. On MVA, AA pts (OR 0.27, p=0.04), boost (OR 2.04, p=0.033), IMN RT (OR 2.73, p=0.003) and PTV V105% (OR=1.002, p=0.03) retained significance. Late grade 2/3 hyperpigmentation was greater in SOC (16% vs 3%, p=0.01). Increased BSP (OR 2.14, p=0.001), AA pts (OR 8.18, p=0.02), bolus and CW boost had greater odds of grade 2/3 hyperpigmentation. On MVA, increased BSP (OR: 3.76, p=0.03) and bolus (OR: 14.1, p=0.01) retained significance.
Conclusion(s): We found less clinician-graded acute RD in SOC and AA pts, less frequent use of topical interventions but more oral analgesic use. We also found higher rates of late pigmentation change with increased BSP independent of race. These findings suggest that RD may be under-diagnosed in SOC. This study confirms the necessity for objective measures of RD that account for variability in BSP to accurately classify the severity of radiation skin toxicity in SOC and treat accordingly.
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