Identification of Key Elements in Prostate Cancer for Ontology Building via a Multidisciplinary Consensus Agreement.

BACKGROUND: Clinical data collection related to prostate cancer (PCa) care is often unstructured or heterogeneous among providers, resulting in a high risk for ambiguity in its meaning when sharing or analyzing data. Ontologies, which are shareable formal (i.e., computable) representations of knowledge, can address these challenges by enabling machine-readable semantic interoperability. The purpose of this study was to identify PCa-specific key data elements (KDEs) for standardization in clinic and research. METHODS: A modified Delphi method using iterative online surveys was performed to report a consensus agreement on KDEs by a multidisciplinary panel of 39 PCa specialists. Data elements were divided into three themes in PCa and included (1) treatment-related toxicities (TRT), (2) patient-reported outcome measures (PROM), and (3) disease control metrics (DCM). RESULTS: The panel reached consensus on a thirty-item, two-tiered list of KDEs focusing mainly on urinary and rectal symptoms. The Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was considered most robust for PROM multi-domain monitoring, and granular KDEs were defined for DCM. CONCLUSIONS: This expert consensus on PCa-specific KDEs has served as a foundation for a professional society-endorsed, publicly available operational ontology developed by the American Association of Physicists in Medicine (AAPM) Big Data Sub Committee (BDSC).

Operational Ontology for Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical and Research Use of Real-World Data From Patients Treated for Cancer.

PURPOSE: The ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), radiation oncology information systems, treatment planning systems, and other cancer care and outcomes databases. We sought to create a standardized ontology for clinical data, social determinants of health, and other radiation oncology concepts and interrelationships. METHODS AND MATERIALS: The American Association of Physicists in Medicine's Big Data Science Committee was initiated in July 2019 to explore common ground from the stakeholders' collective experience of issues that typically compromise the formation of large inter- and intra-institutional databases from EHRs. The Big Data Science Committee adopted an iterative, cyclical approach to engaging stakeholders beyond its membership to optimize the integration of diverse perspectives from the community. RESULTS: We developed the Operational Ontology for Oncology (O3), which identified 42 key elements, 359 attributes, 144 value sets, and 155 relationships ranked in relative importance of clinical significance, likelihood of availability in EHRs, and the ability to modify routine clinical processes to permit aggregation. Recommendations are provided for best use and development of the O3 to 4 constituencies: device manufacturers, centers of clinical care, researchers, and professional societies. CONCLUSIONS: O3 is designed to extend and interoperate with existing global infrastructure and data science standards. The implementation of these recommendations will lower the barriers for aggregation of information that could be used to create large, representative, findable, accessible, interoperable, and reusable data sets to support the scientific objectives of grant programs. The construction of comprehensive "real-world" data sets and application of advanced analytical techniques, including artificial intelligence, holds the potential to revolutionize patient management and improve outcomes by leveraging increased access to information derived from larger, more representative data sets.

Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases: The FAST-01 Nonrandomized Trial.

Importance: To our knowledge, there have been no clinical trials of ultra-high-dose-rate radiotherapy delivered at more than 40 Gy/sec, known as FLASH therapy, nor first-in-human use of proton FLASH. Objectives: To assess the clinical workflow feasibility and treatment-related toxic effects of FLASH and pain relief at the treatment sites. Design, Setting, and Participants: In the FAST-01 nonrandomized trial, participants treated at Cincinnati Children's/UC Health Proton Therapy Center underwent palliative FLASH radiotherapy to extremity bone metastases. Patients 18 years and older with 1 to 3 painful extremity bone metastases and life expectancies of 2 months or more were eligible. Patients were excluded if they had foot, hand, and wrist metastases; metastases locally treated in the 2 weeks prior; metal implants in the treatment field; known enhanced tissue radiosensitivity; and implanted devices at risk of malfunction with radiotherapy. One of 11 patients who consented was excluded based on eligibility. The end points were evaluated at 3 months posttreatment, and patients were followed up through death or loss to follow-up for toxic effects and pain assessments. Of the 10 included patients, 2 died after the 2-month follow-up but before the 3-month follow-up; 8 participants completed the 3-month evaluation. Data were collected from November 3, 2020, to January 28, 2022, and analyzed from January 28, 2022, to September 1, 2022. Interventions: Bone metastases were treated on a FLASH-enabled (≥40 Gy/sec) proton radiotherapy system using a single-transmission proton beam. This is consistent with standard of care using the same prescription (8 Gy in a single fraction) but on a conventional-dose-rate (approximately 0.03 Gy/sec) photon radiotherapy system. Main Outcome and Measures: Main outcomes included patient time on the treatment couch, device-related treatment delays, adverse events related to FLASH, patient-reported pain scores, and analgesic use. Results: A total of 10 patients (age range, 27-81 years [median age, 63 years]; 5 [50%] male) underwent FLASH radiotherapy at 12 metastatic sites. There were no FLASH-related technical issues or delays. The average (range) time on the treatment couch was 18.9 (11-33) minutes per patient and 15.8 (11-22) minutes per treatment site. Median (range) follow-up was 4.8 (2.3-13.0) months. Adverse events were mild and consistent with conventional radiotherapy. Transient pain flares occurred in 4 of the 12 treated sites (33%). In 8 of the 12 sites (67%) patients reported pain relief, and in 6 of the 12 sites (50%) patients reported a complete response (no pain). Conclusions and Relevance: In this nonrandomized trial, clinical workflow metrics, treatment efficacy, and safety data demonstrated that ultra-high-dose-rate proton FLASH radiotherapy was clinically feasible. The treatment efficacy and the profile of adverse events were comparable with those of standard-of-care radiotherapy. These findings support the further exploration of FLASH radiotherapy in patients with cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT04592887.

FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases (FAST-01): Protocol for the First Prospective Feasibility Study.

BACKGROUND: In preclinical studies, FLASH therapy, in which radiation delivered at ultrahigh dose rates of ≥40 Gy per second, has been shown to cause less injury to normal tissues than radiotherapy delivered at conventional dose rates. This paper describes the protocol for the first-in-human clinical investigation of proton FLASH therapy. OBJECTIVE: FAST-01 is a prospective, single-center trial designed to assess the workflow feasibility, toxicity, and efficacy of FLASH therapy for the treatment of painful bone metastases in the extremities. METHODS: Following informed consent, 10 subjects aged ≥18 years with up to 3 painful bone metastases in the extremities (excluding the feet, hands, and wrists) will be enrolled. A treatment field selected from a predefined library of plans with fixed field sizes (from 7.5 cm × 7.5 cm up to 7.5 cm × 20 cm) will be used for treatment. Subjects will receive 8 Gy of radiation in a single fraction-a well-established palliative regimen evaluated in prior investigations using conventional dose rate photon radiotherapy. A FLASH-enabled Varian ProBeam proton therapy unit will be used to deliver treatment to the target volume at a dose rate of ≥40 Gy per second, using the plateau (transmission) portion of the proton beam. After treatment, subjects will be assessed for pain response as well as any adverse effects of FLASH radiation. The primary end points include assessing the workflow feasibility and toxicity of FLASH treatment. The secondary end point is pain response at the treated site(s), as measured by patient-reported pain scores, the use of pain medication, and any flare in bone pain after treatment. The results will be compared to those reported historically for conventional dose rate photon radiotherapy, using the same radiation dose and fractionation. RESULTS: FAST-01 opened to enrollment on November 3, 2020. Initial results are expected to be published in 2022. CONCLUSIONS: The results of this investigation will contribute to further developing and optimizing the FLASH-enabled ProBeam proton therapy system workflow. The pain response and toxicity data acquired in our study will provide a greater understanding of FLASH treatment effects on tumor responses and normal tissue toxicities, and they will inform future FLASH trial designs. TRIAL REGISTRATION: : ClinicalTrials.gov NCT04592887; http://clinicaltrials.gov/ct2/show/NCT04592887. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41812.

Mammary analogue secretory carcinoma presenting with cervical lymphadenopathy: A rare case report with review of the literature.

INTRODUCTION: Mammary analogue secretory carcinoma is a rare malignant tumor of the salivary glands that typically involves the major glands. The aim of the current study is to report a rare case of mammary analogue secretory carcinoma that presented with left cervical lymphadenopathy. CASE REPORT: A 59-year-old lady presented with left cervical lymphadenopathy. Tissue biopsy and immunohistochemistry revealed metastatic carcinoma, favoring ovarian origin. Staging workup was performed and, ultimately, the patient was treated as having a carcinoma of unknown primary. After showing partial response to therapy, left side neck dissection was performed. Based on better assessment of the histologic picture and a broader panel of immunohistochemistry performed on the excision specimen, the final diagnosis was that of mammary analogue secretory carcinoma. DISCUSSION: Mammary analogue secretory carcinoma is usually an indolent salivary gland carcinoma, with the majority of patients presenting with a slow-growing, painless mass measuring approximately 2 cm in size, and a reported duration ranging from 2 months to several years. In certain cases, pain and facial paralysis have been reported. It could also be found incidentally during radiologic assessment for thyroid illness or routine dental screening. CONCLUSION: Diagnosing mammary analogue secretory carcinoma is challenging, and this should be in the differential diagnosis list of metastatic carcinomas to cervical lymph nodes.

Surgical and radiation treatment of a paravertebral malignant solitary fibrous tumor: a case report and literature review.

Malignant solitary fibrous tumors (MSFT) are rare neoplasms, and typically exhibit an aggressive course. While complete surgical resection is the primary treatment modality, the role of adjuvant radiation treatment in larger tumors is not well-established. Despite limited reported cases which demonstrated extended disease-free periods with adjuvant radiation, its utilization is conflictingly both recommended or discouraged across the literature due to the absence of high-quality published data. This is a report to add to the slowly growing body of literature to support the use of adjuvant radiation in these tumors. Specifically, a case of a 64-year-old man who developed rash and mild back pain after a total hip arthroplasty. He was found to have a large paravertebral MSFT, and was treated with surgical resection followed by adjuvant radiation due to size and focally positive margins. He has continued to have no evidence of disease 21 months after treatment. This case of successful treatment and continued disease-free interval with resection and adjuvant radiation contributes valuable supporting data to the management of this rare disease entity. Furthermore, a review of available literature on MSFT treatment is conducted to illustrate the inconsistency in post-surgical management, and demonstrate the necessity of additional detailed reports from a radiation treatment perspective.

Adrenal SBRT: a multi-institutional review of treatment outcomes and toxicity.

The adrenal glands are a common site of metastatic disease. Definitive treatment for oligometastatic disease using ablative radiotherapy is becoming common in modern radiation oncology practice. However, most data on the treatment of adrenal metastases are limited to single institution reports. Furthermore, delivering ablative radiotherapy doses to intra-abdominal lesions can be challenging due to the proximity of the gastrointestinal tract. We report the outcomes of a multi-institutional cohort of patients treated with definitive radiotherapy for adrenal metastases, primarily using 10 fraction regimens. Retrospective review of institutional databases revealed 29 lesions in 27 patients were treated from 2005 to 2018 at two institutions. Outcome data, including local control, disease-free, and overall survival were abstracted from the medical record system. Toxicity was graded using CTCAE v5.0. Detailed radiotherapy data was abstracted from the treatment planning systems. The median dose was 50 Gy in 10 fractions. Actuarial 1 and 2 year local control was 86% and 76% respectively. The median overall and disease-free survival were 22.8 and 5.6 months respectively. There were no associations identified between local failure and GTV and PTV physical or biologic effective dose. Two patients developed late Grade 3 gastrointestinal toxicity. High dose radiotherapy to adrenal metastases is a feasible treatment with excellent local control and a reasonable safety profile. For lesions in close proximity to gastrointestinal structures, moderately hypofractionated 10 fraction regimens may be a reasonable compromise between local control and toxicity.

Renal cell carcinoma and brain metastasis: Questioning the dogma of role for cytoreductive nephrectomy.

INTRODUCTION: Renal cell carcinoma (RCC) brain metastasis is generally viewed as poor prognostic features and often excludes patients from cytoreductive nephrectomy or participation in clinical trials. We aim to evaluate patients presenting with brain metastasis and their outcomes. METHODS: Surveillance Epidemiology and End Results-18 registries database was queried for all patients with metastatic RCC from 2010 to 2014. Patients with renal cancer as their only malignancy were included. Information was available for metastatic disease to bone, liver, lung, and brain. Patients were then further stratified into those with isolated brain metastases and those with additional metastasis to other sites as well. Overall survival was compared between groups using logrank analysis. RESULTS: A total of 6,667 patients were identified with metastatic RCC. Among them, 775 (12.1%) had brain metastasis at time of diagnosis. Of these patients with brain metastasis, 152 (20.4%) had isolated brain metastasis. Only 23.8% of all patients with brain metastasis underwent cytoreductive nephrectomy, compared to 40.8% of patients with isolated brain metastasis. Patients with brain and other metastasis and brain metastasis only treated by cytoreductive nephrectomy exhibited a median survival of 11 and 33 months, respectively. Those patients who did not undergo cytoreductive nephrectomy experienced a median survival of 4 and 5 months, respectively. CONCLUSION: It appears that selected patients with brain metastasis may experience durable long-term survival. This information may be beneficial for patient counseling, surgical planning, and consideration for inclusion in clinical trials.

Institutional experience using interstitial brachytherapy for the treatment of primary and recurrent pelvic malignancies.

PURPOSE: The study assessed the outcomes of patients at a single institution with locally advanced primary and recurrent pelvic malignancies treated with interstitial high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy (BT), using a modified Syed-Neblett template. MATERIAL AND METHODS: Between 1996 and 2010, 60 patients with primary or recurrent pelvic malignancies were treated with interstitial BT. Thirty three patients had primary malignancies with 6.1% being stage I, 33.3% stage II, 45.5% stage III, and 15.2% stage IV; the remaining 27 patients were recurrent malignancies. Fifty four patients received external beam radiotherapy (EBRT) as part of their treatment course. The median EBRT, BT, and EBRT + BT doses were 45 Gy, 20 Gy, and 65 Gy, respectively. Thirty eight patients received concurrent chemotherapy with EBRT. Complete response (CR) was defined by absence of clinical and radiographic disease on first follow-up. Toxicity was graded as per Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The median follow-up was 37 months (4-234 months) and initial CR was achieved in 91%. For primary cancers at diagnosis, 5-year local control (LC), 5-year progression-free survival (PFS), 5-year overall survival (OS) were 65%, 64%, and 42% respectively. For recurrent cancers at diagnosis, 5-year LC, 5-year PFS, and 5-year OS were 80%, 51%, and 37%, respectively. There was a significant difference in both OS and PFS among different tumor sites (p < 0.05), with vaginal cancers having the best 5-year OS (55%) and PFS (84%). There was a total of 1 acute toxicity ≥ grade 3, 6 late grade 3 toxicities, and late grade 4 toxicity. CONCLUSIONS: Our series suggests that interstitial BT using a modified Syed-Neblett template is a safe and effective treatment for primary or recurrent pelvic malignancies. This technique allowed effective LC and 97% of patients had preservation of both bladder and rectal function.

Adjuvant Radiation Improves Survival in Older Women Following Breast-Conserving Surgery for Estrogen Receptor-Negative Breast Cancer.

PURPOSE: Published prospective trials have questioned the role of post-lumpectomy radiotherapy in older women with early-stage, estrogen receptor-positive (ER+) breast cancer. As the population with ER- tumors may be at greater risk for relapse, particularly given that endocrine therapy is not effective, we hypothesize the addition of radiation would be of benefit in patients age ≥ 70. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was queried from 1998 to 2011 for patients age ≥ 70 years receiving breast-conserving surgery for T1, ER- invasive ductal carcinoma. Patients were separated into 2 cohorts: those treated with and without adjuvant radiotherapy. Chi-square analysis, unpaired t test and Kaplan-Meier log-rank were used to compare patient and tumor characteristics as well as overall and cancer-specific survival between the cohorts. RESULTS: Overall, 3685 patients received radiation and 1493 patients received lumpectomy alone. Patients treated with adjuvant radiation were younger (median age 76 vs. 78 years, P < .0001). Patients who received radiation had improved overall survival, with 5-year survival rates of 81.0% versus 61.7% without radiation (P < .0001). Cancer-specific survival was also improved with radiotherapy, with 5-year cancer-specific survival rates of 93.1% versus 85.0% (P < .0001). CONCLUSIONS: This analysis of the SEER database demonstrates that women ages 70 and older treated with lumpectomy and radiotherapy for ER-, early-stage breast cancer have improved overall survival and breast cancer-specific survival compared with patients treated with lumpectomy alone. This information may help in the decision-making process for this patient population.

A successful case of multiple stereotactic radiosurgeries for ipsilateral recurrent trigeminal neuralgia.

Trigeminal neuralgia is a common pain syndrome primarily managed medically, although many patients require surgical or radiotherapeutic intervention. Stereotactic radiosurgery has become a preferred method of treatment given its high efficacy rates and relatively favorable toxicity profile. However, many patients have refractory pain even after repeat courses of stereotactic radiosurgery. Historically, 2 courses have been the limit in such patients. The authors present a case of multiply recurrent trigeminal neuralgia treated with a third course of radiosurgery in which the patient had successful pain control and no additional toxicity. Meticulous attention to the therapeutic technique allows the continued application of stereotactic radiosurgery in patients.