Long-Term Adherence to Adjuvant Endocrine Therapy Following Various Radiotherapy Modalities in Early Stage Hormone Receptor Positive Breast Cancer.

INTRODUCTION: We compared the rates of long-term adjuvant endocrine therapy (AET) adherence after various radiation therapy (RT) modalities among patients with early stage breast cancer. MATERIALS AND METHODS: Medical records from patients with stage 0, I, or IIA (tumors ≤3 cm), hormone receptor (HR) positive breast cancer that received adjuvant radiation therapy (RT) from 2013 to 2015 at a single institution were retrospectively reviewed. All patients received breast conserving surgery (BCS) followed by adjuvant RT via one of the following modalities: whole breast radiotherapy (WBI), partial breast irradiation (PBI) with either external beam radiation therapy (EBRT) or fractionated intracavitary high-dose rate (HDR) brachytherapy, or single fraction HDR-brachytherapy intraoperative-radiation therapy (IORT). RESULTS: One hundred fourteen patients were reviewed. Thirty patients received WBI, 41 PBI, and 43 IORT with a median follow up of 64.2, 72.0, and 58.6 months, respectively. For the entire cohort, AET adherence was approximately 64% at 2 years and 56% at 5 years. Among patients in the IORT clinical trial, adherence to AET was approximately 51% at 2 years and 40% at 5 years. After controlling for additional factors, DCIS histology (vs invasive disease) and IORT (compared to other radiation modalities) were associated with decreased endocrine therapy adherence (P < 0.05). CONCLUSION: DCIS histology and receipt of IORT were associated with lower rates of adherence to AET at 5 years. Our findings suggest that examination of the efficacy of RT interventions such as PBI and IORT in patients who do not receive AET is warranted.

Para-Aortic Nodal Radiation in the Definitive Management of Node-Positive Cervical Cancer.

OBJECTIVES: To investigate the safety and outcomes of elective para-aortic (PA) nodal irradiation utilizing modern treatment techniques for patients with node positive cervical cancer. METHODS: Patients with pelvic lymph node positive cervical cancer who received radiation were included. All patients received radiation therapy (RT) to either a traditional pelvic field or an extended field to electively cover the PA nodes. Factors associated with survival were identified using a Cox proportional hazards model, and toxicities between groups were compared with a chi-square test. RESULTS: 96 patients were identified with a mean follow up of 40 months. The incidence of acute grade ≥ 2 toxicity was 31% in the elective PA nodal RT group and 15% in the pelvic field group (Chi-square p = 0.067. There was no significant difference in rates of grade ≥ 3 acute or late toxicities between the two groups (p>0.05). The KM estimated 5-year OS was not statistically different for those receiving elective PA nodal irradiation compared to a pelvic only field, 54% vs. 73% respectively (log-rank p = 0.11). CONCLUSIONS: Elective PA nodal RT can safely be delivered utilizing modern planning techniques without a significant increase in severe (grade ≥ 3) acute or late toxicities, at the cost of a possible small increase in non-severe (grade 2) acute toxicities. In this series there was no survival benefit observed with the receipt of elective PA nodal RT, however, this benefit may have been obscured by the higher risk features of this population. While prospective randomized trials utilizing a risk adapted approach to elective PA nodal coverage are the only way to fully evaluate the benefit of elective PA nodal coverage, these trials are unlikely to be performed and instead we must rely on interpretation of results of risk adapted approaches like those used in ongoing clinical trials and retrospective data.

8+ Year Performance of the Gamma Knife Perfexion/Icon Patient Positioning System and Possibilities for Preemptive Fault Detection Using Statistical Process Control.

BACKGROUND: The large fractional doses, steep dose gradients, and small targets found in intracranial radiosurgery require extremely low beam delivery uncertainty. In the case of Gamma Knife radiosurgery (GKRS), this includes minimizing patient positioning system (PPS) positioning uncertainty. Existing QA techniques are recipe based, and feature point in time pass/fail tolerances. However, modern treatment machines, including the Gamma Knife Perfexion/Icon systems, record extensive internal data in treatment logs. These data can be analyzed through statistical process control (SPC) methods which are designed to detect changes in process behavior. The purpose of this study was to characterize the long-term (8+ year) performance of a Perfexion/Icon unit and use SPC methods to determine if performance changes could be detected at levels lower than existing QA and internal manufacturer performance tolerances. METHODS: In-house software was developed to parse Perfexion/Icon log-files and store relevant information on shot delivery in a relational database. A last-in, first-out (LIFO) queuing algorithm was created to heuristically match messages associated with a given delivered shot. Filtering criteria were developed to filter QA and uncompleted shots. The resulting matched shots were extracted. Achieved versus planned PPS position was determined for each PPS motor as well as for the vector magnitude difference in PPS position. Exponentially weighted moving average (EWMA) control charts were plotted to determine when process behavior changed over time. RESULTS: 53833 shots were delivered over an 8+ year span in the study. The mean vector magnitude PPS difference was 32.7 µm, with 97.5% of all shots within 70.1 µm. Several changes in PPS positioning behavior were observed over time, corresponding with control system faults on several occasions requiring PPS recalibration. EWMA control charts clearly demonstrate that these faults could be identified and possibly predicted as many as 3 years before there were faults beyond control system tolerance. CONCLUSION: The PPS of Gamma Knife Perfexion/Icon systems has extremely low positioning uncertainties. EWMA control chart method can be utilized to track PPS performance over time and can potentially detect changes in performance that may indicate a component requiring maintenance. This would allow planned service visits to mitigate problems and prevent unplanned downtime.

Clinical Outcomes and Predictors of Lung Toxicity After Multiple Courses of Lung Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: The clinical outcomes of multicourse lung stereotactic body radiotherapy (SBRT) have yet to be validated in a prospective study, and there are a lack of data on allowable composite dosimetry. PATIENTS AND METHODS: Forty-four patients underwent multicourse lung SBRT for recurrent or metachronous NSCLC. The median biologically effective dose (BED10) for the first course and subsequent courses were 132 and 100 Gy, respectively. Patient and treatment characteristics were evaluated to determine the correlation with the development of radiation pneumonitis (RP). RESULTS: The local control rate was 91%. A total of 13.6% developed a grade 2+ RP, and 4.5% developed a grade 3+ RP, including one grade 5. On univariable analysis, multiple composite dosimetric factors (V5 [proportion of lung structure receiving at least 5 Gy], V10, V20, V40, and mean lung dose) were correlated with the development of RP. When comprised of the first and second course of SBRT, a composite lung V5 of < 30% and > 50% was associated with a 0 and 75% incidence of grade 2+ RP, respectively. We identified no significant correlation on multivariable analysis but observed a strong trend between composite lung V5 and the development of grade 2+ RP (hazard ratio, 1.157; P = .058). Evaluation of multiple clinical factors also identified a significant correlation between the timing of repeat lung SBRT and the development of grade 2+ RP after the second course (P = .0028). CONCLUSION: Subsequent courses of lung SBRT, prescribed to a median BED10 of 100 Gy, can provide a high rate of local control with a 4.5% incidence of grade 3+ toxicity. Composite lung V5 and the timing of the second course of lung SBRT may be correlated to the development of RP.

Intracranial disease control for EGFR-mutant and ALK-rearranged lung cancer with large volume or symptomatic brain metastases.

PURPOSE/OBJECTIVE(S): Tyrosine kinase inhibitors (TKIs) are commonly employed for patients with brain metastases from lung cancer and specific driver mutations. We sought to identify the correlation between intracranial tumor burden and outcomes in patients with brain metastases treated with TKIs. MATERIALS/METHODS: We identified and retrospectively reviewed cases of EGFR-mutant or ALK-rearranged lung cancer with brain metastases at any time during their cancer course. Clinical characteristics and treatment information were abstracted from the medical records. Brain metastases were contoured to calculate total volume of disease at diagnosis and after initial therapy. High intracranial burden was defined as either > 10 brain metastases, volume of brain metastases > 15 cc, or largest lesion > 3 cm. Intracranial response was determined according to Response Assessment in Neuro-Oncology (RANO) criteria on the patient level. We determined the correlation between clinical and imaging characteristics and intracranial progression free survival (IC-PFS) and overall survival (OS). RESULTS: Fifty-seven patients with EGFR (n = 49) and ALK (n = 8) alterations were identified. Median follow-up from initial brain metastasis diagnosis was 17 months. Neurological symptoms were present in 54% at brain metastasis diagnosis. For those receiving TKIs alone or TKIs with radiation, at least a partial intracranial response (≥ 65% volume reduction) at 3 months from starting therapy was achieved in 94% and 58%. Progressive intracranial disease at 3 months occurred in 6.3% and 8.3%. Patients with high intracranial burden (n = 21) had a median 17 brain metastases, 6.5 cc volume, and 1.9 cm maximal tumor diameter. Median IC-PFS and OS for patients with high intracranial burden was 13.9 and 35.4 months. Patients with high intracranial burden and neurological symptoms at diagnosis had similar IC-PFS and OS compared to those with low burden and absence of neurological symptoms (p > 0.05 for each). CONCLUSION: Most patients receiving TKIs as part of their initial therapy achieve an early and durable volumetric intracranial response, irrespective of presenting disease burden or neurologic symptoms.

STAT RAD: Prospective Dose Escalation Clinical Trial of Single Fraction Scan-Plan-QA-Treat Stereotactic Body Radiation Therapy for Painful Osseous Metastases.

PURPOSE: Radiation therapy is a well-established treatment for symptomatic bone metastases. Despite continued advances in both planning techniques and treatment delivery, the standard workflow has remained relatively unchanged, often requiring 1 to 3 weeks and resulting in patient inconvenience and delayed palliation. We developed an expedited method wherein computed tomography simulation, treatment planning, quality assurance, and treatment delivery are performed in 1 day. This prospective pilot clinical trial evaluates the safety, efficacy, and patient satisfaction of this rapid workflow. METHODS AND MATERIALS: Patients with 1 to 3 painful bone metastases were prospectively enrolled and treated with 1 fraction of stereotactic body radiation therapy, using a same-day Scan-Plan-QA-Treat workflow, termed STAT RAD, in a phase 1/2 dose escalation trial from 8 Gy to 15 Gy per fraction. Bone pain, opioid use, patient satisfaction, performance status, and quality of life were evaluated before and at 1, 4, 8, 12, 26, and 52 weeks after treatment. Outcomes and treatment-related toxicity were analyzed. RESULTS: A total of 49 patients were enrolled, and 46 patients with 60 bone metastases were treated per the protocol. Partial or greater pain response occurred in 50% of patients at 1 week, 75% of patients at 8 weeks, 68.7% of patients at 6 months, and 33.3% of patients at 12 months. There were 2 grade-3 toxicities, including 1 spinal fracture associated with disease progression and hyperbilirubinemia. Reirradiation was required in 16.7% of treated lesions at a median time to retreatment of 4.9 months. Most patient responses (78.6%) indicated that patients would choose this workflow again. CONCLUSIONS: The results demonstrate that treating bone metastases with palliative stereotactic body radiation therapy via a single-fraction, patient-centric workflow is feasible and safe with doses up to 15 Gy. However, pain response decreased at 12 months and was associated with a 16.7% retreatment rate, which suggests that further dose escalation is warranted.

Central neurocytoma: Clinical characteristics, patterns of care, and survival.

PURPOSE: To investigate clinical characteristics and patterns of care among patients with central neurocytomas in a large cohort of patients. METHODS: The National Cancer Database (NCDB) was queried to identify patients with biopsy confirmed neurocytoma from 2004 to 2015. Patterns of care were described and univariable and multivariable models were performed to investigate the impact of prognostic factors on overall survival. RESULTS: Among 223,404 patients with brain tumors in the NCDB, 868 patients were diagnosed with biopsy-proven neurocytoma and analyzed (0.4% or approximately 75 patients annually). Median age at diagnosis was 31 years and median tumor size was 4-5 cm. Diagnosis was similar between male (49.5%) and female (50.5%). Regarding location, 622 (72%) tumors were intraventricular, 168 (19%) were extra-ventricular, and 78 (9%) overlapping or unspecified. Five-year overall survival among all patients was 89%. On multivariable analysis tumor location, extent of resection, and use of radiation, were not predictive for improved survival (each p > 0.05); however, patient age (p < 0.001), WHO grade (p < 0.001), and medical comorbidity scores (p = 0.002) were independently associated with overall survival. CONCLUSION: Patients with central neurocytoma often present as young adults with sizable tumor burden and are well managed with surgery alone. Considering their favorable survival, efforts to improve tumor control should be carefully weighed against the long-term risks associated with adjuvant therapy like radiation.