Racial and Ethnic Differences in Long-Term Adverse Radiation Therapy Effects Among Breast Cancer Survivors.

PURPOSE: Breast and skin changes are underrecognized side effects of radiation therapy for breast cancer, which may have long-term implications for quality of life (QOL). Racial and ethnic disparities in breast cancer outcomes, including long-term QOL differences after breast radiation therapy, are poorly understood. METHODS AND MATERIALS: We conducted a cross-sectional survey study of patients from the Texas Cancer Registry who received diagnoses of stage 0-II breast cancer from 2009 to 2014 and treated with lumpectomy and radiation therapy; 2770 patients were sampled and 631 responded (23%). The BREAST-Q Adverse Effects of Radiation overall score and subindices measured the effect of radiation therapy on breast tissue. Multivariable logistic regression evaluated associations of demographic and treatment characteristics with outcomes. RESULTS: The median age was 57 years (IQR, 48-65), median time from diagnosis to survey response 9 years (IQR, 7-10), and the cohort included 62 Asian American or Pacific Islander (9.8%), 11 American Indian or Alaskan Native (AIAN) (1.7%), 161 Black (25.5%), 144 Hispanic (22.8%), and 253 White (40.1%) patients. Mean BREAST-Q Adverse Effects of Radiation score was worse for AIAN patients (-22.2; 95% CI, -39.9 to -4.6; P = .01), Black patients (-10.8; 95% CI, -16.1 to -5.5; P < .001), and Hispanic patients (-7.8; 95% CI, -13.0 to -2.5; P = .004) compared with White patients, age <50 compared with ≥65 (effect size -8.6; 95% CI, -14.0 to -3.2; P = .002), less than a college education (-5.8; 95% CI, -10.0 to -1.6; P = .01), bra cup size of D/E versus A/B (-5.3; 95% CI, -9.9 to -0.65; P = .03), and current smokers (-11.3; 95% CI, -18.3 to -4.2; P = .002). AIAN, Black, and Hispanic patients reported worse changes in skin pigmentation, telangiectasias, dryness, soreness, and/or irritation compared with White patients. CONCLUSIONS: AIAN, Black, and Hispanic patients reported substantially worse long-term breast and skin QOL outcomes after radiation therapy. Additional work is needed to understand these differences and how to alleviate them.

Financial toxicity in cancer patients and subsequent risk of repeat acute care utilization.

Background: Acute care (AC) visits by cancer patients are costly sources of healthcare resources and can exert a financial burden of oncology care both for individuals with cancer and healthcare systems. We sought to identify whether cancer patients who reported more severe initial financial toxicity (FT) burdens shouldered excess risks for acute care utilization. Methods: In 225 adult patients who participated in the Economic Strain and Resilience in Cancer (ENRICh) survey study of individuals receiving ambulatory cancer care between March and September 2019, we measured the baseline FT (a multidimensional score of 0-10 indicating the least to most severe global, material, and coping FT burdens). All AC visits, including emergency department (ED) and unplanned hospital admissions, within 1-year follow-up were identified. The association between the severity of FT and the total number of AC visits was tested using Poisson regression models. Results: A total of 18.6% (n = 42) of patients had any AC visit, comprising 64.3% hospital admissions and 35.7% ED visits. Global FT burden was associated with the risk of repeat AC visits within 1-year follow-up (RR = 1.17, 95% CI 1.07-1.29, P < 0.001 for every unit increase), even after adjusting for sociodemographic and disease covariates. When examining subdimensions of FT, the burden of depleted FT coping resources (coping FT) was strongly associated with the risk of repeat AC visits (RR = 1.27, 95% CI 1.15-1.40, P < 0.001) while material FT burden showed a trend toward association (RR = 1.07, 95% CI 0.99-1.15, P = 0.07). Conclusion: In this prospective study of acute oncology care utilization outcomes among adult cancer patients, FT was a predictor of a higher burden of acute care visits. Patients with severely depleted material and also practical and social coping resources were at particular risk for repeated visits. Future studies are needed to identify whether early FT screening and intervention efforts may help to mitigate urgent acute care utilization burdens.

Long-term Patient-Reported Outcomes in a Population-Based Cohort Following Radiotherapy vs Surgery for Oropharyngeal Cancer.

Importance: Oncologic outcomes are similar for patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery or radiotherapy. However, comparative differences in long-term patient-reported outcomes (PROs) between modalities are less well established. Objective: To determine the association between primary surgery or radiotherapy and long-term PROs. Design, Setting, and Participants: This cross-sectional study used the Texas Cancer Registry to identify survivors of OPSCC treated definitively with primary radiotherapy or surgery between January 1, 2006, and December 31, 2016. Patients were surveyed in October 2020 and April 2021. Exposures: Primary radiotherapy and surgery for OPSCC. Main Outcomes and Measures: Patients completed a questionnaire that included demographic and treatment information, the MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) module, the Neck Dissection Impairment Index (NDII), and the Effectiveness of Auditory Rehabilitation (EAR) scale. Multivariable linear regression models were performed to evaluate the association of treatment (surgery vs radiotherapy) with PROs while controlling for additional variables. Results: Questionnaires were mailed to 1600 survivors of OPSCC identified from the Texas Cancer Registry, with 400 responding (25% response rate), of whom 183 (46.2%) were 8 to 15 years from their initial diagnosis. The final analysis included 396 patients (aged ≤57 years, 190 [48.0%]; aged >57 years, 206 [52.0%]; female, 72 [18.2%]; male, 324 [81.8%]). After multivariable adjustment, no significant differences were found between surgery and radiotherapy outcomes as measured by the MDASI-HN (ß, -0.1; 95% CI, -0.7 to 0.6), NDII (ß, -1.7; 95% CI, -6.7 to 3.4), and EAR (ß, -0.9; 95% CI -7.7 to 5.8). In contrast, less education, lower household income, and feeding tube use were associated with significantly worse MDASI-HN, NDII, and EAR scores, while concurrent chemotherapy with radiotherapy was associated with worse MDASI-HN and EAR scores. Conclusions and Relevance: This population-based cohort study found no associations between long-term PROs and primary radiotherapy or surgery for OPSCC. Lower socioeconomic status, feeding tube use, and concurrent chemotherapy were associated with worse long-term PROs. Further efforts should focus on the mechanism, prevention, and rehabilitation of these long-term treatment toxicities. The long-term outcomes of concurrent chemotherapy should be validated and may inform treatment decision making.

Patient-reported Quality of Life After Breast-conserving Surgery With Radiotherapy Versus Mastectomy and Reconstruction.

OBJECTIVE: To compare long-term quality of life (QOL) outcomes in breast cancer survivors who received breast-conserving surgery with radiotherapy (BCS+RT) with those who received a mastectomy and reconstructive surgery (Mast+Recon) without radiotherapy and identify other important factors. BACKGROUND: The long-term differences in patient-reported QOL outcomes following BCS+RT and Mast+Recon are not well understood. METHODS: We identified patients from the Texas Cancer Registry with stage 0-II breast cancer diagnosed in 2009-2014 after BCS+RT or Mast+Recon without radiotherapy. Sampling was stratified by age and race and ethnicity. A paper survey was sent to 4800 patients which included validated BREAST-Q and PROMIS modules. Multivariable linear regression models were implemented for each outcome. Minimal clinically important difference for BREAST-Q and PROMIS modules, respectively, was 4 points and 2 points. RESULTS: Of 1215 respondents (25.3% response rate), 631 received BCS+RT and 584 received Mast+Recon. The median interval from diagnosis to survey completion was 9 years. In adjusted analysis, Mast+Recon was associated with worse BREAST-Q psychosocial well-being (effect size: -3.80, P =0.04) and sexual well-being (effect size: -5.41, P =0.02), but better PROMIS physical function (effect size: 0.54, P =0.03) and similar BREAST-Q satisfaction with breasts, physical well-being, and PROMIS upper extremity function ( P >0.05) compared with BCS+RT. Only the difference in sexual well-being reached clinical significance. Older (≥65) patients receiving BCS+RT and younger (<50) patients receiving autologous Mast+Recon typically reported higher QOL scores. Receipt of chemotherapy was associated with detriments to multiple QOL domains. CONCLUSIONS: Patients who underwent Mast+Recon reported worse long-term sexual well-being compared with BCS+RT. Older patients derived a greater benefit from BCS+RT, while younger patients derived a greater benefit from Mast+Recon. These data inform preference-sensitive decision-making for women with early-stage breast cancer.

Patient-Reported Financial Toxicity in a Population-Based Cohort of Oropharynx Cancer Survivors.

PURPOSE: Patients with oropharyngeal squamous cell carcinoma (OPSCC) are at high risk for financial toxicity (FT), but the nature, extent, and predictors of FT experienced after primary radiation therapy (RT) or surgery are poorly understood. METHODS AND MATERIALS: We used a population-based sample of patients from the Texas Cancer Registry with stage I to III OPSCC diagnosed from 2006 to 2016 and treated with primary RT or surgery. Of 1,668 eligible patients, 1,600 were sampled, 400 responded, and 396 confirmed OPSCC. Measures included the MD Anderson Symptom Inventory Head and Neck, Neck Dissection Impairment Index, and a financial toxicity instrument adapted from the Individualized Cancer Care (iCanCare) study. Multivariable logistic regression evaluated associations of exposures with outcomes. RESULTS: Of 396 analyzable respondents, 269 (68%) received primary RT and 127 (32%) surgery. The median time from diagnosis to survey was 7 years. Due to OPSCC, 54% of patients experienced material sacrifice (including 28% who reduced food spending and 6% who lost their housing), 45% worried about financial problems, and 29% experienced long-term FT. Independent factors associated with more long-term FT included female sex (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.23-2.40), Black non-Hispanic race (OR, 2.98; 95% CI, 1.26-7.09), unmarried status (OR, 1.50; 95% CI, 1.11-2.03), feeding tube use (OR, 3.98; 95% CI, 2.29-6.90), and worst versus best quartile on the MD Anderson Symptom Inventory Head and Neck (OR, 1.89; 95% CI, 1.23-2.90) and Neck Dissection Impairment Index (OR, 5.62; 95% CI, 3.79-8.34). Factors associated with less long-term FT included age >57 years (OR, 0.54; 95% CI, 0.41-0.71; P < .001) and household income ≥$80,000 (OR, 0.60; 95% CI, 0.44-0.82; P = .001). Primary RT versus surgery was not associated with long-term FT (OR, 0.92; 95% CI, 0.68-1.24). CONCLUSIONS: Oropharynx cancer survivors experience high rates of material sacrifice and long-term FT, and we identified important risk factors. Chronic symptom burden was associated with significantly worse long-term financial status, supporting the hypothesis that toxicity mitigation strategies may reduce long-term FT.

Postoperative radiotherapy with modern techniques does not improve survival for operable stage IIIA-N2 non-small cell lung cancer.

OBJECTIVES: This study aims to evaluate whether postoperative radiotherapy using newer techniques (intensity-modulated radiotherapy [IMRT]) is associated with improved survival for patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) who underwent complete resection. METHODS: The overall survival of patients with stage IIIA-N2 NSCLC who received postoperative IMRT versus no postoperative IMRT following induction chemotherapy and lobectomy in the National Cancer Database from 2010-2018 was assessed via Kaplan-Meier analysis, Cox proportional hazards analysis and propensity score-matched analysis. Additional survival analyses were also conducted in patients with completely resected stage IIIA-pN2 NSCLC who had upfront lobectomy (without induction therapy) followed by adjuvant chemotherapy alone or adjuvant chemotherapy with postoperative IMRT. Only patients receiving IMRT, which is a newer, more conformal radiotherapy technique, were included. Patients with positive surgical margins were excluded. RESULTS: A total of 3203 patients with stage IIA-N2 NSCLC who underwent lobectomy were included. Five hundred eighty-eight (18.4%) patients underwent induction chemotherapy followed by lobectomy, and 2615 (82%) underwent lobectomy followed by chemotherapy. In unadjusted, multivariable-adjusted, and propensity score--matched analyses, there were no significant differences in overall survival between the patients who also received postoperative IMRT versus those who did not. CONCLUSIONS: In this national analysis, the use of postoperative IMRT was not associated with improved survival in patients with completely resected stage IIIA-N2 NSCLC with or without induction chemotherapy.

Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention.

PURPOSE/OBJECTIVES: Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. APOE genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of APOE genotype on measures of clinical interest in individuals without a history of cancer. We tested the hypothesis that APOE genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention. MATERIALS AND METHODS: Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50-75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments. RESULTS: Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline (p = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention (p = 0.013) and after 6 months of follow up (p = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not. CONCLUSIONS: APOE genotype may modulate cancer treatment related side effects and symptoms and response to exercise intervention.

Long-term Oncologic Outcomes in Patients with Inflammatory Breast Cancer with Supraclavicular Nodal Involvement.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive subtype of breast cancer characterized by rapid progression and early metastasis, often with advanced nodal locations, including the supraclavicular (SCV) nodal basin. Previously considered M1 disease, ipsilateral clinical supraclavicular node involvement (N3c) disease is now considered locally advanced disease and warrants treatment with intent to cure. The objective of this study was to evaluate the long-term outcomes of patients with IBC and N3c disease. PATIENTS AND METHODS: This study was conducted using a prospectively collected database of all patients with IBC treated at a dedicated cancer center from 2007 to 2019. Surgical patients with SCV nodal involvement and complete follow-up were identified. Our primary outcome was 5-year overall survival (OS). Multivariate Cox proportional hazards models were used to determine predictors for survival. Event-free survival (EFS) and OS were calculated using the Kaplan-Meier method. RESULTS: There were 70 patients who met inclusion criteria. All patients underwent comprehensive trimodality therapy. The majority of patients had complete (66.2%) radiologic response in the SCV nodal basins following neoadjuvant therapy. Six patients (8.6%) had a locoregional recurrence, with two (2.9%) occurring in the supraclavicular fossa. The 5-year OS was 60.2% [95% confidence interval (CI) 47.7-72.7%]. Increasing age (hazard ratio 2.7; p = 0.03) and triple-negative subtype (hazard ratio 4.9; p = 0.03) were associated with poor OS. The 5-year EFS was 56.1% (95% CI 40.9-68.8%). The presence of more than ten positive axillary nodes on final surgical pathology (hazard ratio 5.5; p = 0.01) predicted poor EFS. CONCLUSIONS: With comprehensive trimodality therapy and multidisciplinary team approach, patients with IBC with supraclavicular nodal involvement experience excellent locoregional control and favorable survival.

Perspectives of Zambian Clinical Oncology Trainees in the MD Anderson and Zambia Virtual Clinical Research Training Program (MOZART).

BACKGROUND: African countries are underrepresented in cancer research, partly because of a lack of structured curricula on clinical research during medical education. To address this need, the MD Anderson and Zambia Virtual Clinical Research Training Program (MOZART) was developed jointly by MD Anderson Cancer Center (MDA) and the Cancer Diseases Hospital in Zambia (CDH) for Zambian clinical oncology trainees. We explored participant perspectives to provide insight for implementation of similar efforts. MATERIALS AND METHODS: The MD Anderson and Zambia Virtual Clinical Research Training Program consisted of weekly virtual lectures and support of Zambian-led research protocols through longitudinal mentorship groups that included CDH faculty and MDA peer and faculty mentors. Participants were contacted via email to take part in semi-structured interviews, which were conducted via teleconference and audio-recorded, transcribed, and coded. Emergent themes were extracted and are presented with representative verbatim quotations. RESULTS: Thirteen of the 14 (93%) trainees were interviewed. Emergent themes included (1) participants having diverse educational backgrounds but limited exposure to clinical research, (2) importance of cancer research specific to a resource-constrained setting, (3) complementary roles of peer mentors and local and international faculty mentors, (4) positive impact on clinical research skills but importance of a longitudinal program and early exposure to clinical research, and (5) challenges with executing research protocols. CONCLUSION: To our knowledge, this is the first qualitative study of African clinical oncology trainees participating in a virtual clinical research training program. The lessons learned from semi-structured interviews with participants in MOZART provided valuable insights that can inform the development of similar clinical research training efforts and scale-up.

Building Capacity for Cancer Research in the Era of COVID-19: Implementation and Results From an International Virtual Clinical Research Training Program in Zambia.

PURPOSE: The incidence of cancer in sub-Saharan Africa is increasing rapidly, yet cancer research in the region continues to lag. One contributing factor is limited exposure to clinical research among trainees. We describe implementation and results of a virtual clinical research training program for Zambian clinical oncology fellows developed jointly by the Cancer Diseases Hospital in Zambia and the MD Anderson Cancer Center to address this need. METHODS: The clinical research training program consisted of 14 weekly virtual lectures, development of research questions by Zambian clinical oncology fellows, assignment of faculty and peer mentors, longitudinal mentorship of research protocols, and anonymous precourse and postcourse surveys. The paired t-test was used to analyze the change in academic self-efficacy scores. RESULTS: Fourteen Zambian clinical oncology fellows participated. Senior fellows were paired with research mentors, leading to the development of eight research protocols. A total of 70 meetings and 126 hours of mentorship occurred with a median of seven meetings and 15 hours per pairing. The precourse and postcourse survey response rates were 86% and 79%, respectively. There were statistically significant increases in nine of 12 academic self-efficacy domains. The largest gains were in ability to independently perform research (P < .001) and research mentorship (P = .02) with an average increase of 1.5 points on a five-point scale in both domains. CONCLUSION: The Cancer Diseases Hospital MD Anderson Cancer Center clinical research training program for Zambian clinical oncology fellows led to increases in multiple academic self-efficacy domains among participants, formation of longitudinal mentorship groups with both faculty and peer mentors, and development of Zambian-led research protocols, demonstrating the feasibility of implementing a virtual model. This may be especially relevant because of shifting international collaboration paradigms after the COVID-19 pandemic.

Locoregional Management and Prognostic Factors in Breast Cancer With Ipsilateral Internal Mammary and Axillary Lymph Node Involvement.

PURPOSE: Patients with breast cancer and ipsilateral axillary and internal mammary (IM) lymph node involvement (cN3b) often forgo IM node resection. Therefore, radiation is important for curative therapy. However, prognosis is not well described in the era of modern systemic therapy, and limited data exist to guide optimal locoregional treatment recommendations. METHODS AND MATERIALS: We retrospectively reviewed 117 patients with nonmetastatic cN3b breast cancer treated at our institution between 2014 and 2019. Staging included ultrasound evaluation of all regional nodal basins. All patients received neoadjuvant chemotherapy, resection of the breast primary, and axillary nodal dissection, followed by adjuvant radiation to the breast/chest wall and regional nodes. Institutional guidelines recommend a 10-Gy boost to radiographically resolved nodes, and a 16-Gy boost to unresolved nodes. Overall survival, recurrence-free survival (RFS), locoregional RFS, internal mammary RFS, and distant metastasis-free survival were evaluated with Kaplan-Meier analysis. A multivariable model for RFS was constructed. RESULTS: Median follow-up for 117 patients was 3.82 years. Median age at diagnosis was 46 years and 56 patients (48%) were receptor group ER+/HER2-. Mastectomy was performed in 96 patients (82%), 38 (32%) had biopsy-confirmed IMC involvement, and 8 (7%) had IM node dissection. The median initial radiation dose was 50 Gy (range, 50-55 Gy) and IMC boost 10 Gy (range, 0-16 Gy). The 5-year overall survival, IM RFS, locoregional RFS, distant metastasis-free survival, and RFS were 74%, 98%, 89%, 68%, and 67%, respectively. On multivariable analysis, a clinical complete response of the IM nodes or ypN0 (pathologic complete response of nodes) status had improved 5-year RFS with hazard ratios of 0.24 (P = .006) and 0.27 (P = .05), respectively. Extranodal extension or lymphovascular invasion were associated with worse 5-year RFS with hazard ratios of 4.13 (P = .001) and 2.25 (P = .04), respectively. CONCLUSIONS: Multimodality therapy provides excellent locoregional control of 89% at 5 years for patients with cN3b breast cancer. Adjuvant radiation yields a 5-year IM RFS of 98%. Clinical and pathologic response of IM nodes are independently prognostic for RFS.

Contemporary Outcomes After Multimodality Therapy in Patients With Breast Cancer Presenting With Ipsilateral Supraclavicular Node Involvement.

PURPOSE: Patients with breast cancer and ipsilateral supraclavicular (SCV) node involvement at the time of diagnosis (TNM cN3c) have historically had poor outcomes. Radiation therapy (RT) has an important role because SCV nodes are not routinely surgically dissected. However, optimal locoregional management, contemporary outcomes, and prognostic factors are not well defined. METHODS AND MATERIALS: We reviewed the data of patients with cN3c breast cancer treated at our institution between 2014 and 2019 with curative intent, including neoadjuvant chemotherapy, surgery, and adjuvant RT. All patients received comprehensive regional RT, including to the SCV nodes. Institutional guidelines recommend a 10-Gy or 16-Gy boost to resolved and unresolved N3 nodes, respectively. Overall survival (OS), recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), and supraclavicular recurrence-free survival (SCRFS) were analyzed. RESULTS: Data from 173 consecutive patients were analyzed with a median follow-up time of 2.8 years. The median age was 54 years, 76 patients (44%) were estrogen receptor positive/human epidermal growth factor receptor 2 negative, 100 patients (58%) had T3/4 disease, and 10 patients (6%) underwent a neck dissection. In addition, 156 patients (90%) received a cumulative SCV dose of ≥60 Gy. The 5-year OS, SCRFS, LRRFS, and RFS rates were 73%, 95%, 86%, and 50%, respectively. The 5-year OS rate for a cumulative SCV dose of ≥60 Gy versus <60 Gy was 75% versus 39% (P = .04). In the multivariable analysis, a cumulative SCV dose of ≥60 Gy, extranodal extension, receptor status, and Eastern Cooperative Oncology Group performance status were associated with OS. The 5-year SCRFS rates with and without neck dissection were 100% versus 95% (P = .57). Among patients with a postchemotherapy SCV node size of ≥1 cm without neck dissection, the 5-year SCRFS rate was 83%. CONCLUSIONS: In one of the largest series of patients with cN3c breast cancer, multimodality therapy using adjuvant RT with a SCV boost resulted in a 5-year LRRFS rate of 86%. There is a limited role for neck dissection as the 5-year SCRFS rate was 95% overall and 83% for residual SCV disease ≥1 cm after chemotherapy with RT alone. A cumulative SCV dose of ≥60 Gy was associated with improved OS, but not SCRFS, LRRFS, or RFS. A SCV boost should be considered in these patients as treatment was well-tolerated. Despite advances in systemic therapy, nearly half of patients developed distant metastases, highlighting the need for close observation after treatment.

Management of complications from brain metastasis treatment: a narrative review.

OBJECTIVE: To describe the range of potential side effects associated with modern brain metastasis treatment and provide evidenced-based guidance on the effective management of these side effects. BACKGROUND: Brain metastases are the most commonly diagnosed malignant intracranial tumor and have historically been associated with very poor prognosis. The standard treatment for brain metastases until the 1990s was whole-brain radiation therapy (WBRT) alone. Since then, however, numerous advances have established the role of neurosurgical resection, stereotactic radiosurgery (SRS), targeted systemic therapy, and immunotherapy in the multidisciplinary management of brain metastases and led to improvements in intracranial control, survival, and neurocognitive preservation among patients with brain metastases. As a result, however, brain metastasis treatment is associated with a wider range of potential side effects than ever before, and clinicians are tasked with the challenge of effectively managing these side effects without compromising cancer outcomes. METHODS: We performed a narrative review of peer-reviewed articles related to the management of side effects from multidisciplinary brain metastasis treatment and synthesized the data in the context of our clinical experience and practice. CONCLUSIONS: In this review, we summarize the major complications from intracranial radiotherapy, neurosurgical resection, and brain metastasis directed systemic therapy with corresponding evidenced-based, modern management principles to guide the practicing oncologist.

Stereotactic body ablative radiotherapy for reirradiation of small volume head and neck cancers is associated with prolonged survival: Large, single-institution, modern cohort study.

BACKGROUND: Recurrent head and neck cancer has poor prognosis. Stereotactic body radiotherapy (SBRT) may improve outcomes by delivering ablative radiation doses. METHODS: We reviewed patients who received definitive-intent SBRT reirradiation at our institution from 2013 to 2020. Patterns of failure, overall survival (OS), and toxicities were analyzed. RESULTS: One hundred and thirty-seven patients were evaluated. The median OS was 44.3 months. The median SBRT dose was 45 Gy and median target volume 16.9 cc. The 1-year local, regional, and distant control was 78%, 66%, and 83%, respectively. Systemic therapy improved regional (p = 0.004) and distant control (p = 0.04) in nonmetastatic patients. Grade 3+ toxicities were more common at mucosal sites (p = 0.001) and with concurrent systemic therapy (p = 0.02). CONCLUSIONS: In a large cohort of SBRT reirradiation for recurrent, small volume head and neck cancers, a median OS of 44.3 months was observed. Systemic therapy improved regional and distant control. Toxicities were modulated by anatomic site and systemic therapy.

Evaluating the Soft Tissue Sarcoma Paradigm for the Local Management of Extraskeletal Ewing Sarcoma.

OBJECTIVES: We reviewed our experience treating patients with localized extraskeletal Ewing sarcoma (EES) to determine optimal local management strategies for this rare disease. METHODS: Sixty patients with localized EES treated at our institution between 1994 and 2018 were reviewed. The Kaplan-Meier method was used to estimates disease outcomes. RESULTS: The median follow-up time was 74 months (interquartile range [IQR], 17-121). Half the patients (n = 30) received combined-modality local therapy (CMT) with both surgery and radiation therapy (RT), whereas the other half received single-modality local therapy (SMT) with either surgery or RT. All patients received chemotherapy. The 5-year overall survival was 76%. Twenty-two patients (37%) developed recurrence at a median time of 15 months (IQR, 5-56 months) resulting in 3-year progression-free survival (PFS) of 65%. On univariate analysis, the use of both neoadjuvant and adjuvant chemotherapy was associated with improved 5-year PFS (71% vs. 50%, p = .04) compared with those who received one or the other. Furthermore, 11 patients (18%) developed local recurrences at a median time of 14 months (IQR, 2-19 months), resulting in a 5-year local control (LC) rate of 77%. Use of CMT was not associated with improved LC (83% vs. 72% SMT, p = .41). Also, use of CMT was the only factor associated with poorer disease-specific survival (vs. SMT; hazard ratio, 3.4; p = .047; 95% confidence interval, 1.01-11.4). CONCLUSION: For patients with EES, CMT was not associated with a decreased rate of local relapse. These data suggest that SMT alone may be sufficient for LC in select patients. A multi-institutional collaborative effort should be considered to validate these findings. IMPLICATIONS FOR PRACTICE: Extraskeletal Ewing sarcoma is a rare chemosensitive sarcoma whose clinical course more closely follows Ewing sarcoma of bone rather than that of other soft tissue sarcomas. Based on this study, combined-modality local therapy did not confer a local control advantage compared with single-modality local therapy. Therefore, single-modality local therapy is likely adequate in select patients with favorable disease features, which has the advantage of ensuring prompt administration of systemic therapy. A multi-institutional collaborative effort is warranted to determine which patients may benefit from de-escalated local therapy.

Low risk of radiation myelopathy with relaxed spinal cord dose constraints in de novo, single fraction spine stereotactic radiosurgery.

BACKGROUND AND PURPOSE: Spine stereotactic radiosurgery (SSRS) offers high rates of local control in a critical anatomic area by delivering precise, ablative doses of radiation for treatment of spine metastases. However, the dose tolerance of the spinal cord (SC) after SSRS with relation to radiation myelopathy (RM) is not well-described. MATERIALS AND METHODS: We reviewed patients who underwent single fraction, de novo SSRS from 2012-2017 and received >12 Gy Dmax to the SC, defined using MRI-CT fusion without PRV expansion. The standard SC constraint was D0.01cc ≤ 12 Gy. Local control was estimated with the Kaplan-Meier method. Bayesian analysis was used to compute posterior probabilities for RM. RESULTS: A total of 146 SSRS treatments among 132 patients were included. The median SC Dmax was 12.6 Gy (range, 12.1-17.1 Gy). The SC Dmax was >12 and <13 Gy for 109 (75%) treatments, ≥13 and <14 Gy for 28 (19%) treatments, and ≥14 Gy for 9 (6%) treatments. The 1-year local control rate was 94%. With a median follow-up time of 42 months, there were zero (0) RM events observed. Assuming a prior 4.3% risk of RM, the true rate of RM for SC Dmax of ≤14 Gy was computed as <1% with 98% probability. CONCLUSION: In one of the largest series of patients treated with single fraction, de novo SSRS, there were no cases of RM observed with a median follow-up of 42 months. These data support safe relaxation of MRI-defined SC dose up to D0.01cc ≤ 12 Gy, which corresponds to <1% risk of RM.

Effect of Surgeon Factors on Long-Term Patient-Reported Outcomes After Breast-Conserving Therapy in Older Breast Cancer Survivors.

BACKGROUND: The effect of surgeon factors on patient-reported quality-of-life outcomes after breast-conserving therapy (BCT) is unknown and may help patients make informed care decisions. METHODS: We performed a survey study of women aged ≥ 67 years with non-metastatic breast cancer diagnosed in 2009 and treated with guideline-concordant BCT, to determine the association of surgeon factors with patient-reported outcomes. The treating surgeon was identified using Medicare claims, and surgeon factors were identified via the American Medical Association Physician Masterfile. The primary outcome was patient-reported cosmetic satisfaction measured by the Cancer Surveillance and Outcomes Research Team (CanSORT) Satisfaction with Breast Cosmetic Outcome instrument, while secondary outcomes included BREAST-Q subdomains. All patient, treatment, and surgeon covariables were included in a saturated multivariable linear regression model with backward elimination applied until remaining variables were p < 0.1. RESULTS: Of 1650 women randomly selected to receive the questionnaire, 489 responded, of whom 289 underwent BCT. Median age at diagnosis was 72 years and the time from diagnosis to survey was 6 years. The mean adjusted CanSORT score was higher for patients treated by surgical oncologists than patients treated by non-surgical oncologists (4.01 [95% confidence interval [CI] 3.65-4.38] vs. 3.53 [95% CI 3.28-3.77], p = 0.006). Similarly, mean adjusted BREAST-Q Physical Well-Being (91.97 [95% CI 86.13-97.80] vs. 83.04 [95% CI 80.85-85.22], p = 0.006) and Adverse Radiation Effects (95.28 [95% CI 91.25-99.31] vs. 88.90 [95% CI 86.23-91.57], p = 0.004) scores were better among patients treated by surgical oncologists. CONCLUSIONS: Specialized surgical oncology training is associated with improved long-term patient-reported outcomes. These findings underscore the value of specialized training and may be useful to patients choosing their care team.