Digitally enabled hemovigilance allows real time response to transfusion reactions.

BACKGROUND: Transfusion carries a risk of transfusion reaction that is often underdiagnosed due to reliance on passive reporting. The study investigated the utility of digital methods to identify potential transfusion reactions, thus allowing real-time intervention for affected patients. METHOD: The hemovigilance unit monitored 3856 patients receiving 43,515 transfusions under the hemovigilance program. Retrospective comparison data included 298,498 transfusions. Transfusion medicine physicians designed and validated algorithms in the electronic health record that analyze discrete data, such as vital sign changes, to assign a risk score during each transfusion. Dedicated hemovigilance nurses remotely monitor all patients and perform real-time chart reviews prioritized by risk score. When a reaction is suspected, a hemovigilance trained licensed clinician responds to manage the patient and ensure data collection. Board-certified transfusion medicine physicians reviewed data and classified transfusion reactions under various categories according to the Centers for Disease Control hemovigilance definitions. RESULTS: Transfusion medicine physicians diagnosed 564 transfusion reactions (1.3% of transfusions)-a 524% increase compared to the previous passive reporting. The rapid response provider reached the bedside on average at 12.4 min demonstrating logistic feasibility. While febrile reactions were most diagnosed, recognition of transfusion-associated circulatory overload demonstrated the greatest relative increase. Auditing and education programs further enhanced transfusion reaction awareness. DISCUSSION: The model of digitally-enabled expert real-time review of clinical data that prompts rapid response improved recognition of transfusion reactions. This approach could be applied to other patient deterioration events such as early identification of sepsis.

A 10-Year Experience with Mastectomy and Tissue Expander Placement to Facilitate Subsequent Radiation and Reconstruction.

BACKGROUND: An integrated approach to skin sparing mastectomy with tissue expander placement followed by radiotherapy and delayed reconstruction was initiated in our institution in 2002. The purpose of this study was to assess the surgical outcomes of this strategy. METHODS: Between September 2002 and August 2013, a total of 384 reconstructions had a tissue expander placed at the time of mastectomy and subsequently underwent radiotherapy. Rates and causes of tissue expander explantation before, during, and after radiotherapy, as well as tumor specific outcomes and reconstruction approaches, were collected. RESULTS: Median follow-up after diagnosis was 5.6 (range 1.3-13.4) years. In the study cohort, 364 patients (94.8%) had stage II-III breast cancer, and 7 patients (1.8%) had locally recurrent disease. The 5-year rates of actuarial locoregional control, disease-free survival, and overall survival were 99.2, 86.1, and 92.4%, respectively. The intended delayed-immediate reconstruction was subsequently completed in 325 of 384 mastectomies (84.6% of the study cohort). Of the remaining 59 tissue expanders, 1 was explanted before radiotherapy, 1 during radiotherapy, and 7 patients (1.8%) were lost to follow-up. Fifty patients (13.0%) required tissue expander explantation after radiation and before their planned final reconstruction, primarily due to cellulitis. Nonetheless, the cumulative rate of completed reconstructions was 89.6%. The median time from placement of the tissue expander until reconstruction was 12 (interquartile range 9-15) months. CONCLUSIONS: Tissue expander placement at skin-sparing mastectomy in patients who require radiotherapy appears to be a viable strategy for combining reconstruction and radiotherapy.

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

BACKGROUND: 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. METHODS: From 2011 to 2014, a total of 287 women with American Joint Committee on Cancer stage 0 to stage II breast cancer were randomized to receive CF-WBI (at a dose of 50 grays in 25 fractions plus a tumor bed boost) or HF-WBI (at a dose of 42.56 grays in 16 fractions plus a tumor bed boost) after breast-conserving surgery. Patient-reported outcomes were assessed using the Breast Cancer Treatment Outcome Scale (BCTOS), the Functional Assessment of Cancer Therapy-Breast, and the Body Image Scale and were recorded at baseline and 0.5, 1, 2, and 3 years after radiotherapy. Physician-rated cosmesis was assessed at the same time points. Outcomes by treatment arm were compared at each time point using a 2-sided Student t test. Multivariable mixed effects growth curve models assessed the effects of treatment arm and time on longitudinal outcomes. RESULTS: Of the 287 patients enrolled, 149 were randomized to CF-WBI and 138 were randomized to HF-WBI. At 2 years, the Functional Assessment of Cancer Therapy-Breast Trial Outcome Index score was found to be modestly better in the HF-WBI arm (mean 79.6 vs 75.9 for CF-WBI; P = .02). In multivariable mixed effects models, treatment arm was not found to be associated with longitudinal outcomes after adjusting for time and baseline outcome measures (P≥.14). The linear effect of time was significant for BCTOS measures of functional status (P = .001, improved with time) and breast pain (P = .002, improved with time). CONCLUSIONS: In this randomized trial, longitudinal outcomes did not appear to differ by treatment arm. Patient-reported functional and pain outcomes improved over time. These findings are relevant when counseling patients regarding decisions concerning radiotherapy. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2886-2894. © 2016 American Cancer Society.

Lymph node status in inflammatory breast cancer.

Positive lymph node status in breast cancer is known to be an adverse prognostic factor, but the effect of lymph node (LN) status in inflammatory breast cancer (IBC) has not been evaluated. This study was designed to investigate the association between lymph node status and overall survival (OS) in individuals with IBC. Using the Surveillance, Epidemiology, and End Results (SEER) 18 registry, we collected data on 761 patients diagnosed with non-metastatic IBC from 2004 to 2008. Survival analysis was performed using the Kaplan-Meier method. Cox proportional hazard regression was performed to evaluate univariate and multivariate associations between estrogen and progesterone receptor (ER/PR) status, treatment, and OS. Positive nodal status was associated with a significant decrease in OS (p < 0.001). Five-year survival for LN-positive and LN-negative patients was 49 and 66 %, respectively. In node-positive patients, ER or PR positivity was associated with improved OS, (p = 0.025, p = 0.007). In node-positive patients, the combination of surgery and radiation therapy improved OS when compared with surgery alone (p = 0.002). Nearly 80 % of the patients in this study had nodal metastasis. Positive nodal status was found to be an adverse prognostic factor. ER/PR positivity and treatment with surgery and radiation in node-positive patients was found to improve outcomes. Further studies are required to characterize the biology of IBC and guide the optimal treatment of this disease.

Ethnic disparities in adherence to breast cancer survivorship surveillance care.

BACKGROUND: Adherence to guidelines for surveillance mammography and clinic visits is an important component of breast cancer survivorship care. Identifying ethnic disparities in adherence may lead to improved care delivery and outcomes. METHODS: Records were evaluated for 4535 patients who were treated for stage I, II, or III breast cancer at the University of Texas MD Anderson Cancer Center, Houston, Texas, cancer center between January 1997 and December 2006. Generalized estimating equations and Cox proportional hazards analyses were used to evaluate ethnic differences in missed mammograms and clinic visits up to 4 years of follow-up and the impact of those differences on overall survival. RESULTS: Nonadherence to guidelines for mammography (P = .0002) and clinic visits (P < .0001) increased over time. Hispanic and black patients were more likely to be nonadherent to guidelines for mammography (odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.10-1.65; OR = 1.36, 95% CI = 1.11-1.66, respectively) and clinic visits (OR = 1.62, 95% CI = 1.27-2.06; OR = 1.45, 95% CI = 1.13-1.86, respectively) than white patients. There was an interaction between Hispanic ethnicity and endocrine therapy on nonadherence to mammography guidelines (P = .001). Nonadherence to mammography and clinic visit guidelines was not associated with overall survival. CONCLUSIONS: Withdrawal from breast cancer survivorship care increases over time, and black and Hispanic patients are more likely to be nonadherent. An understanding of the reasons for ethnic disparities in adherence to guidelines for mammography and clinic visits is needed to improve retention in survivorship care.

Timing of infectious complications following breast-conserving therapy with catheter-based accelerated partial breast irradiation.

BACKGROUND: Accelerated partial breast irradiation (APBI) has been used as an alternative to whole-breast irradiation as part of breast-conserving therapy. Indications and outcomes are topics of ongoing investigation. Previous publications have focused on early postoperative infections and reported low rates of delayed infection. We investigated the pattern of infection after catheter-based APBI at our institution. METHODS: Patients who underwent single-entry catheter-based APBI were identified from an institutional prospective registry including data regarding comorbidities and outcomes. Time of infection was calculated from the date of definitive catheter insertion and classified as early (≤30 days) or delayed. RESULTS: A total of 91 breast cancer patients were treated with APBI and enrolled in the registry from 2009 to 2011. The median follow-up was 484 days. Breast infection occurred in 13 (14.3 %), with 3 (3.3 %) occurring within 30 days of catheter placement and 10 (11.0 %) in a delayed fashion. Four patients required hospital admission, five underwent percutaneous aspiration, and one underwent incision and drainage. Eight were treated as outpatients with oral antibiotics alone. CONCLUSIONS: Consistent with other reports, we found an overall infection rate of 14.3 % with single-entry catheter-based APBI. There were substantially fewer infections in the early postoperative period than reported elsewhere, but there were more delayed infections. The intensive follow-up in our study likely identified late infections that may not have otherwise been recognized. Vigilance for infectious complications must continue beyond the immediate treatment period in patients undergoing catheter-based APBI. These infections can range in severity but typically can be managed in an outpatient setting.

Primary tumor extirpation in breast cancer patients who present with stage IV disease is associated with improved survival.

PURPOSE: Previous evaluation of our institutional experience with stage IV breast cancer patients with an intact primary tumor (IPT) did not reveal an overall survival (OS) benefit for surgery at 32.1 months median follow-up. We assessed the impact of surgery after 74.2 months median follow-up, and the effect of systemic therapy and local radiotherapy (RT). METHODS: We reviewed the records of all patients presenting from 1997 to 2002 with stage IV disease with an IPT. Cox proportional hazards modeling was used to assess differences in survival between treatment groups. RESULTS: Seventy-four (35.6 %) of 208 patients underwent resection of the IPT. After adjustment for covariates, surgery was associated with improved OS (p = 0.04). Multivariable analysis revealed that estrogen receptor (ER) positivity (p = 0.002) and having only a single focus of metastatic disease (p = 0.05) were also associated with improved OS. Surgery was highly associated with receipt of RT (p = 0.0003). RT was significantly associated with improved survival (p = 0.015) in an exploratory analysis. CONCLUSIONS: Stage IV breast cancer patients with an IPT treated surgically had significantly improved OS. Radiation to the primary was also associated with improved survival, but this was evident only with adjustment for the effect of surgery. These findings may be limited by selection bias. Completion of ongoing prospective randomized trials is needed to conclusively determine whether stage IV patients with an IPT should be offered aggressive locoregional therapy.

Impact of internal mammary lymph node drainage identified by preoperative lymphoscintigraphy on outcomes in patients with stage I to III breast cancer.

BACKGROUND: Involvement of internal mammary (IM) lymph nodes is associated with a poor prognosis for patients with breast cancer. This study examined the effect of drainage to IM nodes identified by lymphoscintigraphy on oncologic outcomes. METHODS: A prospectively maintained breast cancer patient database at the University of Texas MD Anderson Cancer Center was used to identify patients with stage I to III breast cancer who underwent preoperative lymphoscintigraphy with peritumoral injection of colloid and intraoperative lymphatic mapping from 1996 to 2005. Medical records were reviewed of 1772 patients who had drainage to any lymph node basin on lymphoscintigraphy but who did not undergo IM nodal biopsy. Patients with IM drainage, with or without axillary drainage, were compared with patients without IM drainage. Local-regional recurrence, distant disease-free survival (DDFS), and overall survival were evaluated. RESULTS: We identified IM drainage in 334 patients (18.8%). Patients with IM drainage were significantly younger, less likely to have upper outer quadrant tumors, and more likely to have smaller and medial tumors than patients without IM drainage. Rates of IM irradiation did not differ between the 2 groups. The median follow-up time was 7.4 years. On multivariate analysis, IM drainage was significantly associated with a worse DDFS (hazard ratio, 1.6; 95% confidence interval, 1.03-2.6; P = .04) but not local-regional recurrence or overall survival. CONCLUSIONS: IM drainage on preoperative lymphoscintigraphy was found to be significantly associated with worse DDFS. Further study is needed to determine the role of lymphoscintigraphy in the personalization of breast cancer staging and therapy.

Aligning mission to digital health strategy in academic medical centers.

The strategies of academic medical centers arise from core values and missions that aim to provide unmatched clinical care, patient experience, research, education, and training. These missions drive nearly all activities. They should also drive digital health activities - and particularly now given the rapid adoption of digital health, marking one of the great transformations of healthcare; increasing pressures on health systems to provide more cost-effective care; the pandemic-accelerated funding and rise of well-funded new entrants and technology giants that provide more convenient forms of care; and a more favorable regulatory and reimbursement landscape to incorporate digital health approaches. As academic medical centers emerge from a pandemic-related reactionary digital health posture, where pressures to adopt more digital health technologies mount, a broad digital health realignment that leverages the strengths of such centers is required to accomplish their missions.

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.

Adoption of Ultrahypofractionated Radiation Therapy in Patients With Breast Cancer.

Introduction: The first high-quality clinical trial to support ultrahypofractionated whole-breast irradiation (ultra-HF-WBI) for invasive early-stage breast cancer (ESBC) was published in April 2020, coinciding with the beginning of the COVID-19 pandemic. We analyzed adoption of ultra-HF-WBI for ductal carcinoma in situ (DCIS) and ESBC at our institution after primary trial publication. Methods and Materials: We evaluated radiation fractionation prescriptions for all patients with DCIS or ESBC treated with WBI from March 2020 to May 2021 at our main campus and regional campuses. Demographic and clinical characteristics were extracted from the electronic medical record. Treating physician characteristics were collected from licensure data. Hierarchical logistic regression models identified factors correlated with adoption of ultra-HF-WBI (26 Gy in 5 daily factions [UK-FAST-FORWARD] or 28.5 Gy in 5 weekly fractions [UK-FAST]). Results: Of 665 included patients, the median age was 61.5 years, and 478 patients (71.9%) had invasive, hormone-receptor-positive breast cancer. Twenty-one physicians treated the included patients. In total, 249 patients (37.4%) received ultra-HF-WBI, increasing from 4.3% (2 of 46) in March-April 2020 to a high of 45.5% (45 of 99) in July-August 2020 (P < .001). Patient factors associated with increased use of ultra-HF-WBI included older age (≥50 years old), low-grade WBI without inclusion of the low axilla, no radiation boost, and farther travel distance (P < .03). Physician variation accounted for 21.7% of variance in the outcome, with rate of use of ultra-HF-WBI by the treating physicians ranging from 0% to 75.6%. No measured physician characteristics were associated with use of ultra-HF-WBI. Conclusions: Adoption of ultra-HF-WBI at our institution increased substantially after the publication of randomized evidence supporting its use. Ultra-HF-WBI was preferentially used in patients with lower risk disease, suggesting careful selection for this new approach while long-term data are maturing. Substantial physician-level variation may reflect a lack of consensus on the evidentiary standards required to change practice.

Prospective randomized trial of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus paclitaxel and FAC (TFAC) in patients with operable breast cancer: impact of taxane chemotherapy on locoregional control.

A previous randomized trial (CALGB 9344/Intergroup 0148) compared four cycles of adjuvant doxorubicin/cyclophosphamide (AC) to four cycles of AC plus four cycles of paclitaxel (AC + T) and demonstrated that the addition of paclitaxel improved locoregional control (LRC) in patients with node-positive breast cancer. However, it could not be determined whether it was the paclitaxel or the increased duration of chemotherapy that led to this improvement. The present study aimed to analyze whether the addition of paclitaxel to a doxorubicin-based regimen improves LRC in a cohort of patients who all received eight total cycles of chemotherapy. Five hundred eleven women with operable breast cancer were randomized on a single-institution prospective trial to receive 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) × 8 cycles (n = 252) or FAC × 4 cycles plus paclitaxel × 4 cycles (TFAC) (n = 259). Rates of LRC and overall survival (OS) were analyzed. Median follow-up was 124 months (range 5-167 months). The 10-year LRC rate was 92.6 versus 93.1% in the FAC versus TFAC arms, respectively (P = 0.26). The LRC between treatment arms did not differ when analyzed by locoregional treatment group: breast conservation therapy (BCT), mastectomy alone (M), and mastectomy + radiation (M + RT). The 10-year LRC rates were 95.1% (FAC) versus 91.2% (TFAC) after BCT (P = 0.98), 89.5% (FAC) versus 93.4% (TFAC) after M (P = 0.24), and 94.7% (FAC) versus 96.5% (TFAC) after M + RT (P = 0.59). Additionally, there was no difference in OS between the treatment arms, with 10-year OS rates of 78.4% (FAC) versus 81.7% (TFAC) (P = 0.93). The addition of paclitaxel to a doxorubicin-based regimen had no impact on LRC, regardless of the type of local therapy received. Historically inferior LRC with AC chemotherapy alone versus AC + T may have been due to an inadequate duration of systemic therapy and not due to the absence of paclitaxel.

Proton Accelerated Partial Breast Irradiation: Clinical Outcomes at a Planned Interim Analysis of a Prospective Phase 2 Trial.

PURPOSE: To perform a planned interim analysis of acute (within 12 months) and late (after 12 months) toxicities and cosmetic outcomes after proton accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: A total of 100 patients with pTis or pT1-2 N0 (≤3cm) breast cancer status after segmental mastectomy were enrolled in a single-arm phase 2 study from 2010 to 2019. The clinically determined postlumpectomy target volume, including tumor bed surgical clips and operative-cavity soft-tissue changes seen on imaging plus a radial clinical expansion, was irradiated with passively scattered proton APBI (34 Gy in 10 fractions delivered twice daily with a minimum 6-hour interfraction interval). Patients were evaluated at protocol-specific time intervals for recurrence, physician reports of cosmetic outcomes and toxicities, and patient reports of cosmetic outcomes and satisfaction with the treatment or experience. RESULTS: Median follow-up was 24 months (interquartile range [IQR], 12-43 months). Local control and overall survival were 100% at 12 and 24 months. There were no acute or late toxicities of grade 3 or higher; no patients experienced fat necrosis, fibrosis, infection, or breast shrinkage. Excellent or good cosmesis at 12 months was reported by 91% of patients and 94% of physicians; at the most recent follow-up, these were 94% and 87%, respectively. The most commonly reported late cosmetic effect was telangiectasis (17%). The total patient satisfaction rate for treatment and results at 12 and 24 months was 96% and 100%, respectively. Patients' mean time away from work was 5 days (IQR, 2-5 days), and the median out-of-pocket cost was $700 (IQR, $100-$1600). The mean left-sided heart dose was 2 cGy (range, 0.2-75 cGy), and the mean ipsilateral lung dose was 19 cGy (range, 0.2-164 cGy). CONCLUSIONS: Proton APBI is a maturing treatment option with high local control, favorable intermediate-term cosmesis, high treatment satisfaction, low treatment burden, and exceptional heart and lung sparing.

Five-Year Longitudinal Analysis of Patient-Reported Outcomes and Cosmesis in a Randomized Trial of Conventionally Fractionated Versus Hypofractionated Whole-Breast Irradiation.

PURPOSE: There are limited prospective data on predictors of patient-reported outcomes (PROs) after whole-breast irradiation (WBI) plus a boost. We sought to characterize longitudinal PROs and cosmesis in a randomized trial comparing conventionally fractionated (CF) versus hypofractionated (HF) WBI. METHODS AND MATERIALS: From 2011 to 2014, women aged ≥40 years with Tis-T2 N0-N1a M0 breast cancer who underwent a lumpectomy with negative margins were randomized to CF-WBI (50 Gray [Gy]/25 fractions plus boost) versus HF-WBI (42.56 Gy/16 fractions plus boost). At baseline (pre-radiation), at 6 months, and yearly thereafter through 5 years, PROs included the Breast Cancer Treatment Outcome Scale (BCTOS), Functional Assessment of Cancer Therapy-Breast (FACT-B), and Body Image Scale; cosmesis was reported by the treating physician using Radiation Therapy Oncology Group cosmesis values. Multivariable mixed-effects growth curve models evaluated associations of the treatment arm and patient factors with outcomes and tested for relevant interactions with the treatment arm. RESULTS: A total of 287 patients were randomized, completing a total of 14,801 PRO assessments. The median age was 60 years, 37% of patients had a bra cup size ≥D, 44% were obese, and 30% received chemotherapy. Through 5 years, there were no significant differences in PROs or cosmesis by treatment arm. A bra cup size ≥D was associated with worse BCTOS cosmesis (P < .001), BCTOS pain (P = .001), FACT-B Trial Outcome Index (P = .03), FACT-B Emotional Well-being (P = .03), and Body Image Scale (P = .003) scores. Physician-rated cosmesis was worse in patients who were overweight (P = .02) or obese (P < .001). No patient subsets experienced better PROs or cosmesis with CF-WBI. CONCLUSIONS: Both CF-WBI and HF-WBI confer similar longitudinal PROs and physician-rated cosmesis through 5 years of follow-up, with no relevant subsets that fared better with CF-WBI. This evidence supports broad adoption of hypofractionation with boost, including in patients receiving chemotherapy and in a population with a high prevalence of obesity. The associations of large breast size and obesity with adverse outcomes across multiple domains highlight the opportunity to engage at-risk patients in lifestyle intervention strategies, as well as to consider alternative radiation treatment regimens.

Case Discussion and Literature Review: Cancer Immunotherapy, Severe Immune-Related Adverse Events, Multi-Inflammatory Syndrome, and Severe Acute Respiratory Syndrome Coronavirus 2.

Pediatric, adolescent and young adult (AYA) patients receiving novel cancer immunotherapies may develop associated toxicities with overlapping signs and symptoms that are not always easily distinguished from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/clinical sequelae. We describe 2 diagnostically challenging cases of SARS-CoV-2 and Multi-Inflammatory Syndrome-Adult (MIS-A), in patients with a history of acute lymphoblastic leukemia following cellular therapy administration and review evolving characterization of both the natural course of SARS-CoV-2 infection and toxicities experienced in younger cancer immunotherapy patients. Vigilant monitoring for unique presentations and epidemiologic surveillance to promptly detect changes in incidence of either condition may be warranted.

Among women who experience a recurrence after postmastectomy radiation therapy irradiation is not associated with more aggressive local recurrence or reduced survival.

Recent pre-clinical models suggest that radiation can promote tumor aggressiveness. We hypothesized that if this were occurring clinically, locoregional recurrences (LRRs) after postmastectomy radiation therapy (PMRT) would lead to lower survival than LRR after mastectomy alone. This study used two independent datasets to compare survival after LRR in women treated with versus without PMRT. Data from 229 LRR cases among 1,500 patients enrolled on prospective trials at the MD Anderson Cancer Center (MDA), and 66 LRR cases among 318 patients enrolled in the British Columbia Cancer Agency (BCCA) PMRT randomized trial were analyzed. In the MDA non-randomized dataset, 189/1031 had LRR after mastectomy alone and 40/469 had LRR after PMRT. In the randomized BC trial dataset, 52/158 had LRR after mastectomy alone and 14/160 had LRR after PMRT. In both datasets, survival was calculated from the time of LRR to death. Analysis of MDA data shows that in all LRR cases regardless of distant metastasis (DM), 5/10-year OS were 50/34% without PMRT and 27/19% after PMRT (P = 0.006). However, PMRT-treated patients had increased risk factors for DM (advanced T and N stages) and more PMRT-treated patients developed DM prior to LRR (63 vs. 34%, P = 0.005). Analyzing only patients will an isolated LRR (without previous or simultaneous, DMV), there was no OS difference between groups (P = 0.33). Analysis of BCCA data shows that distributions of T and N stages were similar in patients with LRR after mastectomy alone versus after PMRT. DM free survival after any LRR and after isolated LRR were similar in mastectomy alone versus PMRT-treated patients (P = 0.75, P = 0.26, respectively). Overall survival after any LRR and after isolated LRR were also similar in the two groups (P = 0.93, P = 0.28, respectively). Patients who develop LRR after mastectomy alone have high rates of DM and poor OS but these rates are not affected by the use of PMRT at the time of primary treatment. These data do not support the hypothesis that irradiation promotes biologically aggressive local recurrences.

Outcomes of Curative-Intent Treatment for Patients With Breast Cancer Presenting With Sternal or Mediastinal Involvement.

PURPOSE: Optimal treatment of patients diagnosed with de novo metastatic breast cancer limited to the mediastinum or sternum has never been delineated. Herein, we sought to determine the efficacy of multimodality treatment, including metastasis-directed radiation therapy, in curing patients with this presentation. METHODS AND MATERIALS: This is a single-institution retrospective cohort study of patients with de novo metastatic breast cancer treated from 2005 to 2014, with a 50-month median follow-up for the primary cohort. The primary patient cohort had metastasis limited to the mediastinum/sternum treated with curative intent (n = 35). We also included a cohort of patients with stage IIIC disease treated with curative intent (n = 244). Additional groups included a mediastinal/sternal palliative cohort (treatment did not include metastasis-directed radiation therapy; n = 14) and all other patients with de novo stage IV disease (palliative cohort; n = 1185). The primary study outcomes included locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Cox multivariable models compared survival outcomes across treatment cohorts adjusted for molecular subtype, age, and race. RESULTS: For the mediastinal/sternal curative-intent cohort, 5-year LRRFS was 85%, RFS was 52%, and OS was 63%. After adjustment, there was no statistically significant difference in LRRFS (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.13-1.13; P = .08), RFS (HR, 0.87; 95% CI 0.50-1.49; P = .61), or OS (HR, 0.79; 95% CI 0.44-1.43; P = .44) between the stage IIIC cohort and the mediastinal/sternal curative-intent cohort (referent). In contrast, RFS was worse for the mediastinal/sternal palliative cohort (HR, 2.29; 95% CI 1.05-5.00; P = .04). OS was worst for the de novo stage IV palliative cohort (HR, 2.61; 95% CI 1.50-4.53; P < .001). CONCLUSIONS: For select patients presenting with breast cancer metastatic to the sternum and/or mediastinum, curative-intent treatment with chemotherapy, surgery, and radiation yields outcomes similar to those of stage IIIC disease and superior to de novo stage IV breast cancer treated with palliative intent.

Low-dose and limited-volume radiotherapy alone for primary dural marginal zone lymphoma: treatment approach and review of published data.

PURPOSE: Primary dural lymphoma is a rare intracranial lymphoma that almost always has a marginal zone histologic type and immunophenotype and often remains localized and is thus potentially curable with radiotherapy (RT) alone. The unusual location and histologic type of primary dural marginal zone lymphoma (PDMZL) distinguish it from primary central nervous system lymphoma and poses treatment dilemmas of technique, volume, and dose that have not been well addressed. We set out to analyze our recent experience in treating PDMZL and reviewed the limited published data available. METHODS AND MATERIALS: Between 2002 and 2006, we treated 5 patients with localized PDMZL. Of these 5 patients, 3 had unilateral and 2 had bilateral/multifocal involvement, and 3 underwent subtotal tumor resection and 2 biopsy only. Whole brain RT was given before involved-field RT (IFRT) in 4 patients and 1 received IFRT alone. The median whole brain RT, IFRT, and total RT dose was 20, 12, and 30 Gy, respectively. The planning computed tomography scan was always fused with the post-gadolinium magnetic resonance imaging scan to assist in the IFRT volume determination. We also analyzed the published data from 27 additional patients. RESULTS: The median follow-up was 34 months (range, 31-52). All obtained lasting local control. One patient developed a relapse in the soft tissue of the flank and additional systemic progression but no central nervous system recurrence. At last follow-up, no significant treatment-related neurotoxicity was detected. CONCLUSION: The results of our study have demonstrated that a combination of whole brain RT/IFRT or even low-dose IFRT alone provides excellent durable local control of PDMZL. This approach is potentially curative, possibly without significant neurotoxicity. Additional study and longer follow-up are needed to determine the appropriate RT dose and volume parameters for this rare, debilitating, and yet potentially curable lymphoma.

Risk of subclinical micrometastatic disease in the supraclavicular nodal bed according to the anatomic distribution in patients with advanced breast cancer.

PURPOSE: To determine the anatomic distribution of gross supraclavicular nodes within the supraclavicular fossa using 2-deoxy-2-[F-18] fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans, and to evaluate likely coverage of specific regions of the supraclavicular fossa using standard radiation fields. METHODS AND MATERIALS: We identified 33 patients with advanced or metastatic breast cancer who had a PET/CT scan demonstrating hypermetabolic supraclavicular lymph nodes in 2005. The locations of the involved lymph nodes were mapped onto a single CT set of images of the supraclavicular fossa. These lymph nodes were also mapped onto the treatment-planning CT dataset of 4 patients treated in our institution (2 patients with biopsy-proven supraclavicular nodes and 2 patients with clinically negative supraclavicular nodes). RESULTS: We were able to determine the distribution of 52 supraclavicular lymph nodes in 32 patients. Of 32 patients, 28 (87%) had a history of metastatic disease, and 2 patients had isolated nodal recurrences. Five patients had supraclavicular nodes posterior to the vertebral body transverse process, and several lymph nodes were in close proximity to the medial field border, raising the possibility of geographic miss in these areas. CONCLUSIONS: In patients with locally advanced disease, increased coverage of the supraclavicular fossa medially and posteriorly may be warranted.