Gergelis, Kimberly R.

Physician burnout is prevalent and contributes to the high number of physicians choosing to leave clinical practice. The field of hematology-oncology (HO) poses unique challenges for trainees and staff physicians who have to deliver bad news, manage complicated psychosocial situations, deal with the limited ability to prolong life, and juggle multiple time-sensitive demands from coworkers, patients, and families. Furthermore, they often face the death of their patients, along with its emotional toll on patients’ families and the physicians themselves. Burnout in HO is prevalent and increasing, with many physicians reporting in several studies that they plan to reduce working hours and/or retire early. The demand for hematologists and oncologists is rapidly rising, but in the setting of a worsening HO workforce shortage and an increasing number of patients with cancer. Therefore, it is imperative to develop strategies to mitigate or address burnout in HO physicians to improve well-being and prevent attrition. Herein, we describe risk factors and causes of physician burnout in HO trainees and practicing physicians in the United States, with a focus on institutional and individual strategies to address this issue. We also provide recommendations to address the burnout epidemic from the HO standpoint.

Purpose: This study aimed to compare long-term patient-reported outcomes in bowel and urinary domains between intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) for localized prostate cancer. Methods and Materials: Patients with clinical T1–T2 prostate cancer receiving IMRT or IMPT at a tertiary cancer center from 2015–2018 were analyzed to determine the changes in the prospectively collected bowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC-26. The mean changes in EPIC-26 scores were evaluated from pretreatment to 24 months post-radiotherapy for each modality. A score change >50% of the baseline standard deviation was considered a clinically meaningful change. Results: A total of 82 patients treated with IMRT (52.2%) and 56 patients treated with IMPT (53.3%) completed the questionnaire at baseline and 24 months post-RT. There were no baseline differences in domain scores between treatment modalities. At 24 months post-radiotherapy, there was a significant and clinically meaningful decline in the BF mean score in the IMRT cohort (−4.52 (range −50, 29.17), p = 0.003), whereas the decline in BF score did not reach clinical relevance or significance (−1.88 (range −37.5, 50), p = 0.046) when accounting for the Bonferroni adjustment in the IMPT cohort. A higher proportion of patients treated with IMRT had a clinically relevant reduction in BF when compared with IMPT (47.37% vs. 25.93%, p = 0.017). The mean changes in the UI and UO scores of the IMRT and IMPT cohorts were neither statically significant nor clinically relevant. Conclusions: IMPT leads to a smaller decrease in BF than IMRT at 24 months post-RT, while there was no differential effect on UO and UI.

Abstract Background In breast cancer patients treated with pencil‐beam scanning proton therapy (PBS), the increased linear energy transfer (LET) near the end of the proton range can affect nearby ribs. This may associate with a higher risk of rib fractures. Purpose To study the effect of LET on rib fracture in breast cancer patients treated with PBS using a novel tool of dose‐LET volume histogram (DLVH). Methods From a prospective registry of patients treated with post‐mastectomy proton therapy to the chest wall and regional lymph nodes for breast cancer between 2015 and 2020, we retrospectively identified rib fracture cases detected after completing treatment. Contemporaneously treated control patients who did not develop rib fracture were matched to patients 2:1 considering prescription dose, boost location, reconstruction status, laterality, chest wall thickness, and treatment year. The DLVH index, V (d, l), defined as volume( V ) of the structure with at least dose(d) and dose‐averaged LET (l) (LETd), was calculated. DLVH plots between the fracture and control group were compared. Conditional logistic regression (CLR) model was used to establish the relation of V (d, l) and the observed fracture at each combination of d and l . The p ‐value derived from CLR model shows the statistical difference between fracture patients and the matched control group. Using the 2D p ‐value map derived from CLR model, the DLVH features associated with the patient outcomes were extracted. Results Seven rib fracture patients were identified, and fourteen matched patients were selected for the control group. The median time from the completion of proton therapy to rib fracture diagnosis was 12 months (range 5–14 months). Two patients had grade 2 symptomatic rib fracture while the remaining 5 were grade 1 incidentally detected on imaging. The derived p ‐value map demonstrated larger V (0–36 Gy[RBE], 4.0–5.0 keV/µm) in patients experiencing fracture ( p < 0.1). For example, the p ‐value for V (30 Gy[RBE], 4.0 keV/um) was 0.069. Conclusion In breast cancer patients receiving PBS, a larger volume of chest wall receiving moderate dose and high LETd may result in an increased risk of rib fracture.

Abstract Background: Sarcopenia, characterized by the loss of muscle mass, has emerged as a negative prognostic factor in cancer patients. It has been associated with poorer outcomes and increased treatment-related morbidity. Post-mastectomy breast radiation therapy (RT) increases the likelihood of reconstructive complication, with up to 20% of reconstructed women requiring implant removal. The factors that lead to these complications are poorly understood and likely multifaceted. We investigated the relationship between pre-radiation therapy sarcopenia and post-mastectomy reconstruction outcomes. Methods: Chart review was performed to determine demographic, medical, and treatment variables, including reconstruction complication events and failures in breasts treated with mastectomy, immediate reconstruction, and RT. Reconstruction failure was defined as tissue expander or implant removal, resulting in no final reconstruction or autologous reconstruction only. Reconstruction complications included surgical site infection, late infection (1 year post-RT), seroma development, flap necrosis, nipple necrosis, wound dehiscence, capsular contracture, hematoma, extrusion, leak, venous congestion, and unplanned reoperation. An axial slice at the L2 or L3 vertebral body from the radiation therapy planning CT scan was analyzed for skeletal muscle area using a previously validated algorithm, with manual review and adjustment as indicated. Sarcopenia was defined by skeletal muscle index (SMI, skeletal muscle area in cm2 divided by patient’s height squared) below 34.4 cm2/m2. Chi-square, Kaplan Meier, and univariate Cox regression tests were used for analysis. Results: Ninety-nine women with breast cancer who underwent mastectomy, reconstruction, and RT were included in this study. All women had immediate reconstruction: 93 women had tissue expander placement while six women had permanent implant placement. Mean age was 47.5 years (SD 10.6) at diagnosis and median BMI was 24.8. Seventy-six percent were non-smokers, 24% were former smokers, and only 16 (16.2%) and 3 (3.0%) had hypertension or diabetes, respectively. Median follow-up was 2.7 years. Median SMI was 38 cm2/m2 and 18 (18%) met criteria for sarcopenia (SMI &lt; 34.4 cm2/m2). Mastectomy was bilateral in 79 women, skin-sparing in 61, and nipple sparing in 31. Bilateral mastectomy was less frequent amongst women with sarcopenia (61%) compared to 84% of those without sarcopenia (p=0.03). After RT, twenty-three women required unplanned reoperation. Within these 23 women, there were 45 total complications. Complications included surgical site infection (n=18), capsular contracture (n=12), seroma (n=4), wound dehiscence (n=3), and others (n=8). However, only 8 women had reconstructive failure and none were sarcopenic at the time of the RT planning scan. Any complication or failure after RT occurred in similar proportions of patients with and without sarcopenia: 38% and 30%, respectively. Kaplan-Meier curves and univariate Cox regression models showed no significant difference in time to failure (p = 0.380) or time to any event (complication or failure) (p=0.53), between sarcopenic and non-sarcopenic patients. Conclusion: Sarcopenia, using SMI &lt; 34.4 cm2/m2 on pre-radiotherapy planning scans, was not associated with an increased risk of post-radiotherapy reconstructive complication or failure in this selected cohort of non-smokers. Few women had sarcopenia at the time of operation, and results should be validated in a larger series. Citation Format: Yasamin Sharifzadeh, Robert Gao, William S. Harmsen, Jason Klug, Panagiotis Korfiatis, Kimberly Gergelis, Dean A. Shumway, Robert Mutter, Kimberly Corbin. Sarcopenia and Post-Mastectomy Breast Reconstruction Outcomes after Radiation Therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-52.

Objectives We evaluated the outcomes of metastatic pancreatic cancer (MPC) patients who underwent liver metastases (LMs)–directed ablative radiotherapy (RT) and sought to characterize patients with more favorable prognosis. Methods A retrospective analysis of 76 MPC patients who underwent ablative RT (median dose, 50 Gy) to LM at 3 academic centers between 2008 and 2018 was performed. Endpoints were local control (LC), progression-free survival, and overall survival (OS) since RT. Results Median follow-up was 10.9 months. Liver metastases were metachronous in 68%. Before RT, LM was responsive/stable on chemotherapy (CTX) in 36% whereas progressive in 43%. Median carbohydrate antigen 19-9 (CA 19-9) at RT was 334 U/mL. After RT, 32% had ≥6 months of CTX break. Twelve-month outcomes were: LC, 66%; progression-free survival, 7%; and OS, 38%. On multivariable analysis, Eastern Cooperative Oncology Group 2–3 (hazard ratio [HR], 13.49; P < 0.01), progressive LM on CTX (HR, 3.26; P < 0.01), and higher CA 19-9 (log 10 scale; HR, 1.39; P < 0.01) at RT predicted worse OS. Conclusions Ablative RT to LM in setting of MPC may offer LC of systemic disease and thus quality time off CTX. Selected patients with good performance status, stable/responsive LM on CTX, and lower CA 19-9 have more favorable prognosis.

AbstractPurposeTo prospectively assess acute differences in patient‐reported outcomes in bowel and urinary domains between intensity‐modulated radiotherapy (IMRT) and proton beam therapy (PBT) for prostate cancer.Methods and MaterialsBowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC‐26 were collected in patients with T1‐T2 prostate cancer receiving IMRT or PBT at a tertiary cancer center (2015‐2018). Mean changes in domain scores were analyzed from pretreatment to the end of and 3 months post‐radiotherapy for each modality. A clinically meaningful change was defined as a score change >50% of the baseline standard deviation.ResultsA total of 157 patients receiving IMRT and 105 receiving PBT were included. There were no baseline differences in domain scores between cohorts. At the end of radiotherapy, there was significant and clinically meaningful worsening of BF and UO scores for patients receiving either modality. In the BF domain, the IMRT cohort experienced greater decrement (−13.0 vs −6.7, P < .01), and had a higher proportion of patients with clinically meaningful reduction (58.4% vs 39.5%, P = .01), compared to PBT. At 3 months post‐radiotherapy, the IMRT group had significant and clinically meaningful worsening of BF (−9.3, P < .001), whereas the change in BF score of the PBT cohort was no longer significant or clinically meaningful (−1.2, P = .25). There were no significant or clinically meaningful changes in UO or UI 3 months post‐radiotherapy.ConclusionsPBT had less acute decrement in BF than IMRT following radiotherapy. There was no difference between the two modalities in UO and UI.

305 Background: Toxicity due to radiotherapy (RT) may differ in patients (pts) with prostate cancer who receive intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). Methods: Patient-reported bowel function (BF), urinary incontinence (UI), and urinary irritative/obstructive symptoms (UO) domains of the Expanded Prostate Index Composite Questionnaire (EPIC-26) were prospectively collected in pts with localized prostate cancer receiving either IMRT (n=157) or PBT (n=105) to the prostate +/- proximal seminal vesicles for clinical stage T1-T2 N0 prostate cancer at a single tertiary cancer center between 2015 and 2018. Changes in domain scores were analyzed from pretreatment to the end of RT and 3 months post-RT, assessing the acute effects of each modality. A clinically relevant change was defined as a score change that exceeded 50% of the standard deviation of a baseline value. Results: At baseline there was no difference in the scores of BF, UI, and UO domains between IMRT and PBT cohorts. At the end of RT, pts treated with either modality had a statistically significant and clinically relevant worsening of BF and UO compared to baseline. Pts treated with IMRT experienced a significantly greater decrement in BF compared to the PBT cohort (-13 vs -9, p<0.01), including significantly more IMRT pts having a clinically relevant deterioration in BF compared to PBT pts (58% vs 40%, p=0.01). Though there was a statistically significant deterioration in UI in the IMRT cohort (-4, p<0.001), this did not reach the predefined threshold for clinical relevance. Three months following RT, the IMRT group continued to have statistically significant and clinically relevant worsening of BF (-9, p<0.001), whereas the change in BF domain score of the PBT cohort was no longer statistically significant or clinically relevant compared to baseline (-1, p=0.25). There were no statistically significant or clinically relevant changes in UO or UI in either cohort at three months when compared to baseline. Conclusions: Pts who received IMRT or PBT reported unique patterns of toxicity, and pts treated with IMRT had worse decrement in BF immediately after and three months following RT, compared to those treated with PBT.