Innovations in research and clinical care using patient-generated health data.

Patient-generated health data (PGHD), or health-related data gathered from patients to help address a health concern, are used increasingly in oncology to make regulatory decisions and evaluate quality of care. PGHD include self-reported health and treatment histories, patient-reported outcomes (PROs), and biometric sensor data. Advances in wireless technology, smartphones, and the Internet of Things have facilitated new ways to collect PGHD during clinic visits and in daily life. The goal of the current review was to provide an overview of the current clinical, regulatory, technological, and analytic landscape as it relates to PGHD in oncology research and care. The review begins with a rationale for PGHD as described by the US Food and Drug Administration, the Institute of Medicine, and other regulatory and scientific organizations. The evidence base for clinic-based and remote symptom monitoring using PGHD is described, with an emphasis on PROs. An overview is presented of current approaches to digital phenotyping or device-based, real-time assessment of biometric, behavioral, self-report, and performance data. Analytic opportunities regarding PGHD are envisioned in the context of big data and artificial intelligence in medicine. Finally, challenges and solutions for the integration of PGHD into clinical care are presented. The challenges include electronic medical record integration of PROs and biometric data, analysis of large and complex biometric data sets, and potential clinic workflow redesign. In addition, there is currently more limited evidence for the use of biometric data relative to PROs. Despite these challenges, the potential benefits of PGHD make them increasingly likely to be integrated into oncology research and clinical care.

Pediatric Central Nervous System Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Central nervous system (CNS) cancers account for approximately one quarter of all pediatric tumors and are the leading cause of cancer-related death in children. More than 4,000 brain and CNS tumors are diagnosed each year in children and teens, and the incidence rate has remained stagnant in recent years. The most common malignant pediatric CNS tumors are gliomas, embryonal tumors consisting of predominately medulloblastomas, and germ cell tumors. The inaugural version of the NCCN Guidelines for Pediatric Central Nervous System Cancers focuses on the diagnosis and management of patients with pediatric diffuse high-grade gliomas. The information contained in the NCCN Guidelines is designed to help clinicians navigate the complex management of pediatric patients with diffuse high-grade gliomas. The prognosis for these highly aggressive tumors is generally poor, with 5-year survival rates of <20% despite the use of combined modality therapies of surgery, radiation therapy and systemic therapy. Recent advances in molecular profiling has expanded the use of targeted therapies in patients whose tumors harbor certain alterations. However, enrollment in a clinical trial is the preferred treatment for eligible patients.

Increased Risk for Ipsilateral Breast Tumor Recurrence in Invasive Lobular Carcinoma after Accelerated Partial Breast Irradiation Brachytherapy.

BACKGROUND: The suitability criteria for accelerated partial breast irradiation (APBI) from the American Brachytherapy Society (ABS), American Society for Radiation Oncology (ASTRO), and The Groupe Européende Curiethérapie European SocieTy for Radiotherapy & Oncology (GEC-ESTRO) have significant differences. MATERIALS AND METHODS: This is a single institution retrospective review of 946 consecutive patients with invasive breast cancer who underwent lumpectomy and APBI intracavitary brachytherapy from 2003 to 2018. Overall survival (OS), breast cancer-specific survival (BCSS), relapse-free survival (RFS), and ipsilateral breast tumor recurrence (IBTR) were estimated with Kaplan-Meier method. RESULTS: Median follow-up time was 60.2 months. Median age was 68 years (46-94 years). The majority of patients had estrogen receptor (ER)-positive disease (94%). There were 821 (87%) cases of invasive ductal carcinoma and 68 cases (7%) of invasive lobular carcinoma (ILC). The 5-year OS, BCSS, RFS, and IBTR were 93%, 99%, 90%, and 1.5%, respectively. Upon univariate analysis, ILC (hazard ratio [HR], 4.6; p = .008) and lack of nodal evaluation (HR, 6.9; p = .01) were risk factors for IBTR. The 10-year IBTR was 2.5% for IDC and 14% for ILC. While the ABS and ASTRO criteria could not predict IBTR, the GEC-ESTRO intermediate risk group was associated with inferior IBTR (p = .04) when compared to both low risk and high risk groups. None of the suitability criteria was able to predict RFS. CONCLUSION: These results show that APBI is an effective treatment for patients with invasive breast cancer. Expansion of the current eligibility criteria should be considered, although prospective validation is needed. Caution is required when considering APBI for patients with ILC. IMPLICATIONS FOR PRACTICE: In a large retrospective review of 946 patients with early breast cancer treated with partial mastectomy and accelerated partial breast irradiation (APBI) intracavitary brachytherapy, this study demonstrates durable local control. Patients deemed unsuitable or high risk by the American Brachytherapy Society, American Society for Radiation Oncology, and European Society for Radiotherapy and Oncology guidelines were not at increased risk for ipsilateral breast tumor recurrence (IBTR), suggesting that expansion of the current criteria should be considered. Importantly, however, these results demonstrate that caution should be taken when considering APBI for patients with invasive lobular carcinoma, as these patients had relatively high risk for IBTR (10-year IBTR, 14%).

The Role of Radiation Therapy in the Older Patient.

PURPOSE OF REVIEW: Older patients represent a unique subgroup of the cancer patient population for which the role of radiation therapy (RT) requires special consideration. This review will discuss many of these considerations as well as various radiation treatment techniques in the context of a variety of disease sites. RECENT FINDINGS: Several recent studies give insight into the management of older cancer patients considering their age, performance status, comorbid conditions, quality of life, genetics, cost, and individual goals. RT plays an evolving and pivotal role in providing optimal care for this population. Recent advances in RT technique allow for more precise treatment delivery and reduced toxicity. Studies evaluating the use of radiation therapy in breast, brain, lung, prostate, rectal, pancreatic, esophageal, and oligometastatic cancer are summarized and discussed in the context of treating the older patient population. Individual age, performance and functional status, comorbid conditions, and patients' objectives and goals should all be considered when presenting treatment options for older patients and age alone should not disqualify patients from curative intent treatments. When possible, hypofractionated courses should be utilized as outcomes are often equivalent and toxicities are reduced. In many cases, RT may be preferable to other treatment options due to decreased toxicity profile and acceptable disease control.

Pediatric Acute Lymphoblastic Leukemia, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Advancements in technology that enhance our understanding of the biology of the disease, risk-adapted therapy, and enhanced supportive care have contributed to improved survival rates. However, additional clinical management is needed to improve outcomes for patients classified as high risk at presentation (eg, T-ALL, infant ALL) and who experience relapse. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric ALL provide recommendations on the workup, diagnostic evaluation, and treatment of the disease, including guidance on supportive care, hematopoietic stem cell transplantation, and pharmacogenomics. This portion of the NCCN Guidelines focuses on the frontline and relapsed/refractory management of pediatric ALL.

Patient-reported outcomes regarding radiation therapy in patients with multiple myeloma.

Background: Radiation therapy (RT) has been widely used for palliation in multiple myeloma. However, no data exist on symptom assessment and patient-reported outcomes regarding the efficacy of RT in this disease process. This study aims to demonstrate the impact of palliative RT on patient-reported symptoms in patients with multiple myeloma.Materials and Methods: Our Radiation Oncology and Supportive Care Medicine clinics established the use of a modified Edmonton Symptom Assessment Scale (ESAS) in 2015 assessing 12 symptom domains. All had ESAS data available from each encounter. Demographic and clinical data were retrospectively collected from an institutional data warehouse. We examined total and component survey scores for correlated data of patients during radiation treatment and patients not treated with radiation.Results: Clinic records of 30 patients with multiple myeloma seen in the Radiation Oncology and Supportive Care clinics from 2015 to 2018 were retrieved. A total of 91 discrete surveys were collected (1183 data points). Twenty of these were collected from weekly visits from 12 patients receiving RT; the remainder were from new patient or follow up encounters. Odds ratios were lower with radiation therapy for total scores (OR 4.86, p = .007), as well as several component scores.Conclusions: The use of palliative RT was associated with 5 times lower total symptom scores compared with nonuse. Similar beneficial results were found for several component scores. These patient-reported outcomes strongly suggest that providers should consider palliative radiation for symptomatic multiple myeloma patients. These data should be prospectively validated in a larger cohort of myeloma patients.

Health care disparities among octogenarians and nonagenarians with stage III lung cancer.

BACKGROUND: To the authors' knowledge, the practice patterns for patients aged more than 80 years with stage III non-small cell lung cancer (NSCLC) is not well known. The purpose of the current study was to investigate factors predictive of and the impact on overall survival (OS) after concurrent chemoradiation (CRT) among patients aged ≥80 years with American Joint Committee on Cancer stage III NSCLC in the National Cancer Data Base (NCDB). METHODS: In the NCDB, patients aged ≥80 years who were diagnosed with stage III NSCLC from 2004 to 2013 with complete treatment records were identified. Multivariable logistic regression and Cox proportional hazard models were generated and propensity score-matched analysis was used. RESULTS: A total of 12,641 patients met the entry criteria: 6018 (47.6%) had stage IIIA disease and 6623 (52.4%) had stage IIIB disease. The median age at the time of diagnosis was 83.0 years (range, 80-91 years). A total of 7921 patients (62.7%) received no therapy. Black race (odds ratio [OR], 1.23; 95% confidence interval [95% CI], 1.06-1.43) and living in a lower educated census tract of residence (OR, 1.20; 95% CI, 1.03-1.40) were found to be associated with not receiving care, whereas treatment at an academic center (OR, 0.80; 95% CI, 0.70-0.92) was associated with receiving cancer-directed therapy. Receipt of no treatment (hazard ratio [HR], 2.69; 95% CI, 2.57-2.82) or definitive radiation alone (HR, 1.15; 95% CI, 1.07-1.24) compared with CRT was associated with worse OS. On propensity score matching, not receiving CRT was found to be associated with worse OS (HR, 1.58; 95% CI, 1.44-1.72). CONCLUSIONS: In this NCDB analysis, approximately 62.7% of patients aged ≥80 years with stage III NSCLC received no cancer-directed care. Black race and living in a lower educated census tract were associated with not receiving cancer-directed care. OS was found to be improved in patients receiving CRT. Cancer 2018;124:775-84. © 2018 American Cancer Society.

Whole lung irradiation in stage IV Wilms tumor patients: Thyroid dosimetry and outcomes.

PURPOSE: To report the thyroid dosimetry and long-term follow-up of childhood cancer survivors treated with whole lung irradiation (WLI) for Wilms tumor. METHODS: Twenty-eight patients with pulmonary metastases from Wilms tumor who underwent WLI from 2000 TO 2012 at a single institution were reviewed. Radiation dose to the thyroid gland in each case was calculated. Postradiation thyroid function test (TFT) results and management of thyroid function abnormalities were extracted from the medical records. RESULTS: Median age at treatment was 5 years (range: 1-9 years), and median follow-up time was 74.1 months (7.2-198.4). The male/female ratio was 1:1.8. Complete dosimetry data were available for 22 of the 28 patients receiving WLI. Mean thyroid volume was 3.3 cc (range: 1-6.8). The average mean and median mean dose to the thyroid was 6.7 and 7.1 Gy, respectively (range: 1.3-11.7 Gy). Average max dose to the thyroid was 12.4 Gy (range: 7.8-20.3 Gy). Two patients were found to have a thyroid stimulating hormone (TSH) above the normal range, managed with levothyroxine. Another patient was found to have an isolated elevation of TSH which normalized without treatment. A fourth patient was found to have an enlarged thyroid on examination with no palpable nodules or abnormal TFTs. CONCLUSIONS: Average mean dose to the thyroid gland was 6.7 Gy for this population of stage IV Wilms tumor patients. There was a low rate of thyroid dysfunction, but limited follow-up. Attention to blocking the thyroid gland as much as possible when designing radiation fields can potentially mitigate the risks of long-term thyroid effects.

Early outcomes and patterns of failure following proton therapy for nonmetastatic intracranial nongerminomatous germ cell tumors.

BACKGROUND: Although dosimetric comparisons demonstrate the advantage of proton therapy (PT) over conventional radiotherapy for nongerminomatous germ cell tumors (NGGCT), clinical outcome data for this rare tumor are lacking. We sought to evaluate outcomes for children with NGGCT treated with PT. METHODS: Between 2007 and 2016, 14 children (median age 11, range, 5-19 years) with nonmetastatic NGGCT were treated with PT after induction chemotherapy. Most (8/14) were mixed germ cell. Five of 14 patients had complete resection of their primary tumor before radiation. Off study, eight patients received 36 Gy (RBE [relative biological effectiveness]) craniospinal irradiation (CSI). On study, two patients received 30.6 Gy (RBE) whole-ventricle irradiation and four received focal radiation alone. All patients received a total dose of 54 Gy (RBE) to the tumor/tumor bed. RESULTS: At a median follow-up of 2.8 years, all patients were alive with no local recurrences. Three-year progression-free survival was 86%. Both metastatic recurrences occurred in patients treated with focal radiation alone; one with an immature teratoma developed an isolated spinal recurrence 5 months after treatment. Another with a mixed germ cell tumor developed a multifocal ventricular and shunt tract recurrence 7 months after treatment. Serious toxicity was minimal, including cataracts and hormone deficiency, and limited to children who received CSI. CONCLUSION: Early outcomes in children treated for NGGCT suggest the high conformality of PT does not compromise disease control and yields low toxicity. This pattern of failure data adds to growing evidence suggesting chemotherapy followed by focal radiotherapy alone is inadequate in controlling localized NGGCT.

Outcomes following proton therapy for pediatric ependymoma.

BACKGROUND: Proton therapy can reduce the low and intermediate radiation dose to uninvolved brain tissue in children with intracranial ependymomas, which may improve functional outcomes and reduce second malignancies in survivors. Accordingly, ependymoma has become the most common pediatric tumor treated with proton therapy, yet data on efficacy and toxicity are limited. MATERIAL AND METHODS: Between June 2007 and February 2017, 179 children (≤21 years old) with nonmetastatic grade II/III intracranial ependymoma received proton therapy at our institution. Median age, 3.5 years (range, 0.7-21); 58% were male. Most (66%) tumors were in the posterior fossa and classified as WHO grade III (67%). 27% underwent multiple operations to maximize the extent of resection; ultimately 85% had a gross total or near total tumor resection before radiotherapy. 33% received preradiation chemotherapy. Median radiation dose in children ≤3 years old, 54 Gy(RBE). Most (>90%) children over 3 years old received 59.4 Gy(RBE). Patient and treatment variables were assessed for correlation with disease control. RESULTS: Median follow-up, 3.2 years. 3-year local control, progression-free survival, and overall survival rates were 85%, 76%, and 90%, respectively. First site of progression was local, metastatic, or simultaneous in 14, 17 and 6 patients, respectively. On multivariate analysis, subtotal resection was associated with inferior local control (67% vs. 88%; p ≤ .01) and progression-free survival (59% vs. 79%; p < .05). Male sex was associated with inferior progression-free (67% vs. 87%; p< .05) and overall survival (84% vs. 99%; p < .01). The 3-year CTCAE grade 2 + brainstem toxicity rate was 5.5% (95% CI: 2.9-10.2), including 1 grade 5 toxicity. CONCLUSIONS: This series of proton therapy for pediatric intracranial ependymoma demonstrates disease control comparable to photon series without unexpected toxicity. Subtotal resection and male sex were associated with inferior disease control. Additional follow-up to quantify the expected reductions in late toxicity with proton therapy is ongoing.

The Effect of Transition Clinics on Knowledge of Diagnosis and Perception of Risk in Young Adult Survivors of Childhood Cancer.

BACKGROUND: Improved treatment for pediatric cancers has ensured an evergrowing population of patients surviving into adulthood. The current study evaluated the impact of previous engagement in survivor care on patient knowledge and awareness of health risks as young adults. PROCEDURE: Young adult survivors of childhood cancers (N=93, M age=23.63 y) were recruited during their annual survivor clinic visit. Participants completed self-reported measures of demographics, treatment knowledge, perception of future health risks, participation in previous survivor care, and neurocognitive functioning. RESULTS: In total, 82% of patients (N=76/93) reported previously participating in survivorship care. These patients were more likely to have knowledge of their radiation treatment (P=0.034) and more likely to recognize risk for future health effects from their treatment (P=0.019). Income between $10,000 and $24,999 (odds ratio=0.168; 95% confidence interval, 0.046-0.616; P=0.031) was associated with decreased patient knowledge regarding diagnosis. Male sex (odds ratio=0.324; 95% confidence interval, 0.135-0.777; P=0.012) was associated with less knowledge of future health risks. Patients with self-reported difficulties on the CCSS-NCQ were more likely to regard their cancer treatment as a future health risk. CONCLUSION: Participation in survivor care plays an important role in imparting information to young adult survivors of pediatric cancer regarding their disease history and risk for future health problems.

Stereotactic body radiation therapy versus no treatment for early stage non-small cell lung cancer in medically inoperable elderly patients: A National Cancer Data Base analysis.

BACKGROUND: Stereotactic body radiation therapy (SBRT) has demonstrated high rates of local control with low morbidity and has now emerged as the standard of care for medically inoperable, early stage non-small cell lung cancer (NSCLC). However, the impact of lung SBRT on survival in the elderly population is less clear given competing comorbid conditions. An analysis of the National Cancer Data Base (NCDB) was undertaken to determine whether definitive SBRT improves survival relative to observation alone patients ages 70 years and older. METHODS: The NCDB, a retrospective national database that captures approximately 70% of all patients treated for cancer, was queried for patients aged 70 years or older with early stage (T1-T3N0M0) NSCLC from 2003 to 2006. Overall survival was compared between patients who received stereotactic body radiotherapy alone and those who received no treatment. An extended Cox proportional hazards model was applied to estimate the treatment effect of SBRT. RESULTS: In total, 3147 patients met the selection criteria for this analysis. SBRT was delivered to 258 patients (8.2%), and 2889 patients (91.8%) received no treatment. There was no significant difference in the distribution of Charlson/Deyo comorbidity index scores between the 2 groups (P = .076). Multivariable analysis revealed improved overall survival with SBRT compared with observation for the entire cohort (hazard ratio, 0.64; P < .001). CONCLUSIONS: SBRT is associated with improved survival in elderly patients with early stage NSCLC who have concurrent comorbid conditions compared with observation alone. The current data support the use of SBRT for the treatment of elderly patients with early stage NSCLC who have limiting comorbid conditions.

Neoadjuvant modified FOLFIRINOX and chemoradiation therapy for locally advanced pancreatic cancer improves resectability.

BACKGROUND AND OBJECTIVES: Though necessary for improved outcomes, surgical resection is often limited in patients with locally advanced pancreatic cancers (LAPCs). We evaluated the efficacy of the approach adopted by our institution of using modified FOLFIRINOX chemotherapy followed by radiation with concurrent gemcitabine or capecitabine for patients with LAPCs, in an effort to enhance resectability while improving the toxicity profile compared with similar treatment regimens. METHODS: We included 29 consecutive patients with LAPC treated at our institution with the above approach in this review. We evaluated rates of resection, locol control, and survival outcomes in this cohort. RESULTS: The median follow up for this series of patients was 15.2 months. Approximately half the patients were unresectable at presentation. After neoadjuvant therapy, 41.3% of all patients were able to undergo resection of their tumors and 83% achieved an R0 resection. One-year local control for the entire cohort was 85%; one-year progression-free and overall were 49.2% and 65.5%, respectively. High rates of metastatic disease were seen regardless of resectability. There were minimal toxicities in this cohort. CONCLUSIONS: Neoadjuvant therapy with induction modified FOLFIRINOX and chemoradiation presents a well-tolerated, promising treatment approach for patients with LAPC. High rates of metastatic disease highlight the need to optimize systemic and targeted agents for pancreatic adenocarcinoma.

Outcomes After Radiation Therapy to Metastatic Sites in Patients With Stage 4 Neuroblastoma.

In patients with high-risk metastatic neuroblastoma, the benefit of radiation therapy (RT) to metastatic sites as part of primary treatment has not been fully investigated. The purpose of this single-institution study was to evaluate local control of irradiated metastatic sites, and characterize metastatic disease burden and anatomic distribution in patients with high-risk metastatic neuroblastoma. The records of all patients diagnosed with stage 4 neuroblastoma between August 2000 and January 2010 were reviewed. Exclusion criteria included: bone-marrow only metastatic site, total body irradiation, or no imaging follow-up. A total of 37 patients met eligibility criteria. Median follow-up period for patients without relapse was 61 months. Five-year overall survival for all patients was 67%. Thirteen patients (35%) received RT to a metastatic site as part of their primary treatment. Among these patients, in-field recurrence occurred in three patients (23%), including two of three treated calvarial sites. In patients treated with or without RT to a metastatic site, respectively, there was no significant difference in 5-year overall survival (73% vs. 63%, P=0.84) or relapse-free survival (46% and 55%, P=0.48). Current metastatic site RT dose may be suboptimal, and certain locations may predict for a poor response. Further studies are necessary to elucidate the optimal role of RT to metastatic sites.

The feasibility of frameless stereotactic radiosurgery in the management of pediatric central nervous system tumors.

Recurrent malignant primary and metastatic central nervous system (CNS) tumors in pediatric patients are devastating, and efforts to improve outcomes for these patients have been disappointing. Conventional re-irradiation in these patients increases the risk of significant toxicity. We therefore evaluated feasibility and outcomes using frameless radiosurgery (FRS) in children with recurrent primary and metastatic brain tumors. We reviewed five cases of recurrent primary and metastatic brain tumors treated with frameless radiosurgery between 2008 and 2013. We analyzed safety and feasibility, dosimetric data, local control, and adverse effects. Five patients were treated with frameless radiosurgery for palliation. Fifteen target volumes were treated using our institutional FRS system. The volumes of targets ranged from 0.08 to 51.67 cm(3) with doses ranging from 15 to 21 Gy. Radiosurgery was well tolerated, decreased the need for large-volume CNS irradiation, and allowed for effective palliation in this small cohort. Frameless radiosurgery is feasible in this patient population. Frameless radiosurgery should be considered in management of select patients with recurrent primary or metastatic brain tumors.

Thirty-day mortality as a metric for palliative radiotherapy in pediatric patients.

PURPOSE OF REVIEW: Thirty-day mortality (30DM) is an emerging consideration for determining whether terminally ill adult patients may benefit from palliative radiotherapy (RT). However, the efficacy and ethics of delivering palliative RT at the end of life (EOL) in children are seldom discussed and not well-established. RECENT FINDINGS: Palliative RT is perhaps underutilized among patients ≤21 years old with rates as low as 11%. While effective when delivered early, clinical benefit decreases when administered within the last 30 days of life. Pediatric 30DM rates vary widely between institutions (0.7-30%), highlighting the need for standardized practices. Accurate prognosis estimation remains challenging and prognostic models specific to palliative pediatric patients are limited. Discordance between provider and patient/parent perceptions of prognosis further complicates decision-making. SUMMARY: RT offers effective symptom control in pediatric patients when administered early. However, delivering RT within the last 30 days of life may provide limited clinical benefit and hinder optimal EOL planning and care. Early referral for palliative RT, preferably with fewer fractions (five or fewer), along with multidisciplinary supportive care, optimizes the likelihood of maintaining patients' quality of life. Prognosis estimation remains difficult, and improving patient and family understanding is crucial. Further research is needed to refine prognostic models and enhance patient-centered care.

Risks of Spinal Abnormalities and Growth Impairment After Radiation to the Spine in Childhood Cancer Survivors: A PENTEC Comprehensive Review.

PURPOSE: A PENTEC (Pediatric Normal Tissue Effects in the Clinic) review was performed to estimate the dose-volume effects of radiation therapy on spine deformities and growth impairment for patients who underwent radiation therapy as children. METHODS AND MATERIALS: A systematic literature search was performed to identify published data for spine deformities and growth stunting. Data were extracted from 12 reports of children irradiated to the spine (N = 603 patients). The extracted data were analyzed to find associations between complication risks and the radiation dose (conventional fractionation throughout) as impacted by exposed volumes and age using the mixed-effects logistic regression model. When appropriate, corrections were made for radiation modality, namely orthovoltage beams. RESULTS: In the regression analysis, the association between vertebral dose and scoliosis rate was highly significant (P < .001). Additionally, young age at time of radiation was highly predictive of adverse outcomes. Clinically significant scoliosis can occur with doses ≥15 Gy to vertebrae during infancy (<2 years of age). For children irradiated at 2 to 6 years of age, overall scoliosis rates of any grade were >30% with doses >20 Gy; grade 2 or higher scoliosis was correlated with doses ≥30 Gy. Children >6 years of age remain at risk for scoliosis with doses >30 Gy; however, most cases will be mild. There are limited data regarding the effect of dose gradients across the spine on degree of scoliosis. The risk of clinically meaningful height loss was minimal when irradiating small volumes of the spine up to 20 Gy (eg, flank irradiation), except in infants who are more vulnerable to lower doses. Growth stunting was more frequent when larger segments of the spine (eg, the entire spine or craniospinal irradiation) were irradiated before puberty to doses >20 Gy. The effect was modest when patients were irradiated after puberty to doses >20 Gy. CONCLUSIONS: To reduce the risk of kyphoscoliosis and growth impairment, the dose to the spine should be kept to <20 Gy for children <6 years of age and to <10 to 15 Gy in infants. The number of vertebral bodies irradiated and dose gradients across the spine should also be limited when possible.

Management of ductal carcinoma in situ with accelerated partial breast irradiation brachytherapy: Implications for guideline expansion.

PURPOSE: Accelerated partial breast irradiation (APBI) for patients with ductal carcinoma in situ (DCIS) is controversial, and the suitability criteria from the American Brachytherapy Society (ABS), American Society of Therapeutic Radiology and Oncology (ASTRO), and the European Society for Radiotherapy and Oncology (GEC-ESTRO) have important differences. METHODS AND MATERIALS: This is a single-institution retrospective review of 169 consecutive patients with DCIS who underwent lumpectomy followed by APBI intracavitary brachytherapy from 2003 to 2018. Outcomes, including overall survival, recurrence-free survival (RFS), ipsilateral breast tumor recurrence, and distant metastasis, were estimated with the Kaplan-Meier method. RESULTS: The median followup time was 62.5 months. Median age was 66 years (47-89 years). The majority of patients had estrogen receptor-positive disease (89%). Fifty patients (30%) had Grade 3 disease. Of the 142 patients with adequate pathology interpretation, 91 and 108 cases had margins ≥ 3 mm and ≥2 mm, respectively. Most patients (72%) were prescribed and started endocrine therapy. Of the patients evaluable for ABS criteria (N = 130), 97 met the suitability criteria. Of the patients evaluable for ASTRO criteria (N = 129), 42 were deemed cautionary and 33 were deemed unsuitable. Of the patients evaluable for GEC-ESTRO criteria (N = 143), 141 cases were at intermediate risk and two were at high risk. Five-year ipsilateral breast tumor recurrence, RFS, and overall survival were 0.6%, 97.7%, and 97.2%, respectively. The ABS, ASTRO, and GEC-ESTRO criteria failed to significantly predict for RFS. CONCLUSIONS: These results, although limited by short-term followup, indicate that expansion of the eligibility criteria of APBI for patients with DCIS should be considered.

The prevalence of luminal B subtype is higher in older postmenopausal women with ER+/HER2- breast cancer and is associated with inferior outcomes.

OBJECTIVES: To establish whether clinicopathologic and genomic characteristics may explain the poor prognosis associated with advanced age in ER+/HER2- breast cancer. MATERIALS AND METHODS: The cohort included 271 consecutive post-menopausal patients with ER+/HER2- invasive breast cancer ages 55 years and older. Patients were categorized as "younger" (ages 55- < 75) and "older" (ages ≥75). The Kaplan-Meier method was used to estimate locoregional recurrence (LRR), recurrence-free interval (RFi), and overall survival (OS). Gene expression of tumor samples was assessed with Affymetrix Rosetta/Merck Human RSTA microarray platform. Differential gene expression analysis of tumor samples was performed using R package Limma. RESULTS: 271 breast cancer patients were identified, including 186 younger and 85 older patients. Older patients had higher rates of Luminal B subtype (53% vs 34%) and lower rates of Luminal A subtype (42% vs 58%, p = 0.02). Older patients were less likely to receive chemotherapy (9% vs 40%, p < 0.001) and hormone therapy (71% vs 89%, p < 0.001). For cases of grade 1-2 disease, older patients had a higher proportion of the luminal B subtype (49% vs. 30%, p = 0.014). Age ≥ 75 predicted for inferior OS (HR = 3.06, p < 0.001). The luminal B subtype predicted for inferior OS (HR = 2.12, p = 0.014), RFi (HR 5.02, p < 0.001), and LRR (HR = 3.12, p = 0.045). There were no significant differences in individual gene expression between the two groups. CONCLUSION: Women with ER+/HER2- breast cancer ≥75 years old had higher rates of the more aggressive luminal B subtype and inferior outcomes. Genomic testing of these patients should be strongly considered, and treatment should be intensified when appropriate.

Correlation of Acute and Late Brainstem Toxicities With Dose-Volume Data for Pediatric Patients With Posterior Fossa Malignancies.

PURPOSE: Radiation-induced brainstem toxicity after treatment of pediatric posterior fossa malignancies is incompletely understood, especially in the era of intensity modulated radiation therapy (IMRT). The rates of, and predictive factors for, brainstem toxicity after photon RT for posterior fossa tumors were examined. METHODS AND MATERIALS: After institutional review board approval, 60 pediatric patients treated at our institution for nonmetastatic infratentorial ependymoma and medulloblastoma with IMRT were included in the present analysis. Dosimetric variables, including the mean and maximum dose to the brainstem, the dose to 10% to 90% of the brainstem (in 10% increments), and the volume of the brainstem receiving 40, 45, 50, and 55 Gy were recorded for each patient. Acute (onset within 3 months) and late (>3 months of RT completion) RT-induced brainstem toxicities with clinical and radiographic correlates were scored using Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Patients aged 1.4 to 21.8 years underwent IMRT or volumetric arc therapy postoperatively to the posterior fossa or tumor bed. At a median clinical follow-up period of 2.8 years, 14 patients had developed symptomatic brainstem toxicity (crude incidence 23.3%). No correlation was found between the dosimetric variables examined and brainstem toxicity. Vascular injury or ischemia showed a strong trend toward predicting brainstem toxicity (P=.054). Patients with grade 3 to 5 brainstem toxicity had undergone treatment to significant volumes of the posterior fossa. CONCLUSION: The results of the present series demonstrate a low, but not negligible, risk of brainstem radiation necrosis for pediatric patients with posterior fossa malignancies treated with IMRT. No specific dose-volume correlations were identified; however, modern treatment volumes might help limit the incidence of severe toxicity. Additional work investigating inherent biologic sensitivity might also provide further insight into this clinical problem.