American Society of Clinical Oncology 2022 Annual Meeting Highlights for Radiation Oncologists.

The American Society of Clinical Oncology annual meeting is the largest multidisciplinary oncology-focused conference in the world. With almost 5000 total abstracts in 2022, it is difficult for individuals to evaluate all the results. Here we present a review of 28 selected abstracts, across all disease sites, focusing on those of greatest relevance to radiation oncologists.

Unsealed Source: Scope of Practice for Radiopharmaceuticals Among United States Radiation Oncologists.

Purpose: Our purpose was to determine the utilization of and barriers to implementation of radiopharmaceutical therapy (RPT) among U.S. radiation oncologists. Methods and Materials: An anonymous, voluntary 21-item survey directed toward attending radiation oncologists was distributed via social media platforms (Twitter, LinkedIn, Facebook, Student Doctor Network). Questions assessed practice characteristics, specific RPT prescribing patterns, RPT prescribing interest, and perceived barriers to RPT implementation. Nonparametric χ2 test was used for correlation statistics. Results: Of the 142 respondents, 131 (92.3%) practiced in the United States and were included for this analysis. Respondents were well balanced in terms of practicing region, population size served, practice setting, and years in practice. Forty-eight percent (n = 63) reported prescribing at least 1 RPT. An additional 7% (n = 8) participate in RPT administration without billing themselves. Among those that actively prescribed RPT, the mean cumulative cases per month was 4.2 (range, 1-5). The most commonly prescribed radionuclides were radium-223 (40%; mean 2.8 cases/mo), iodine-131 (18%; mean 2.3 cases/mo), yttrium-90 (13%; mean 3.4 cases/mo), "other" (8%), samarium-153 (6%; mean 1.0 cases/mo), and strontrium-89 and phosphorous-32 (2% each; mean 1.8 and 0.4 cases/mo, respectively). Of those who answered "other," lutetium-177 dotatate was most commonly prescribed (8%). No significant (P < .05) association was noted between practice type, practice location, years of practice, or practice volume with utilization of any RPTs. Most radiation oncologists (56%, n = 74) responded they would like to actively prescribe more RPT, although 27% (n = 35) were indifferent, and 17% (n = 22) said they would not like to prescribe more RPT. Perceived barriers to implementation were varied but broadly categorized into treatment infrastructure (44%, n = 57), interspecialty relations (41%, n = 53), lack of training (23%, n = 30), and financial considerations (16%, n = 21). Conclusions: Among surveyed U.S. radiation oncologists, a significant number reported prescribing at least 1 RPT. The majority expressed interest in prescribing additional RPT. Wide-ranging barriers to implementation exist, most commonly interspecialty relations, treatment infrastructure, lack of training, and financial considerations.

The Use of Low-Dose Radiation Therapy in Osteoarthritis: A Review.

Despite its clinical use and investigation in other countries, low dose radiation therapy (LDRT) in the treatment of osteoarthritis (OA) is minimally used in the United States (US). Numerous recent studies published outside the US have shown moderate to long-term pain relief and improvement of mobility after treatment with LDRT for joints affected by OA. Here, we review the most recent literature published on the use of LDRT in OA. We provide a brief outline on the epidemiology, pathophysiology, current treatments, and health care burden of OA within the US. We provide a brief history of the historic use of LDRT in the US as well as a history of LDRT within the modern era of radiation oncology, discuss criticisms of LDRT including recently published randomized trials questioning its benefit as well as the risk of secondary malignancy from LDRT, and provide an outline of treatment planning considerations and recommendations regarding dose and fractionation, energy, beam arrangements, and immobilization techniques. LDRT has been shown to be a cost-effective, noninvasive treatment with minimal side effects. Further investigation into the potential role in the treatment of OA with modern LDRT is recommended.

Correction to 'Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity'.

[This corrects the article DOI: 10.1093/narcan/zcab021.].

Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity.

Topoisomerase inhibitors are potent DNA damaging agents which are widely used in oncology, and they demonstrate robust synergistic tumor cell killing in combination with DNA repair inhibitors, including poly(ADP)-ribose polymerase (PARP) inhibitors. However, their use has been severely limited by the inability to achieve a favorable therapeutic index due to severe systemic toxicities. Antibody-drug conjugates address this issue via antigen-dependent targeting and delivery of their payloads, but this approach requires specific antigens and yet still suffers from off-target toxicities. There is a high unmet need for a more universal tumor targeting technology to broaden the application of cytotoxic payloads. Acidification of the extracellular milieu arises from metabolic adaptions associated with the Warburg effect in cancer. Here we report the development of a pH-sensitive peptide-drug conjugate to deliver the topoisomerase inhibitor, exatecan, selectively to tumors in an antigen-independent manner. Using this approach, we demonstrate potent in vivo cytotoxicity, complete suppression of tumor growth across multiple human tumor models, and synergistic interactions with a PARP inhibitor. These data highlight the identification of a peptide-topoisomerase inhibitor conjugate for cancer therapy that provides a high therapeutic index, and is applicable to all types of human solid tumors in an antigen-independent manner.

An Evaluation of Health Numeracy among Radiation Therapists and Dosimetrists.

PURPOSE: Medical errors in radiation oncology sometimes involve tasks reliant on practitioners' grasp of numeracy. Numeracy has been shown to be suboptimal across various health care professionals. Herein, we assess health numeracy among American Society of Radiologic Technologists (ASRT) members. METHODS AND MATERIALS: The Numeracy Understanding for Medicine instrument (NUMi), an instrument to measure numeracy in the general population, was adapted to oncology for this study and distributed to ASRT members (n = 14,228) in 2017. Per NUMi scoring, health numeracy scores were categorized as low (0-7), low average (8-12), high average (13-17), or high (18-20). The impact of cGy versus Gy on numeracy performance was investigated. Spearman's rho and a Wilcox-Mann-Whitney test were used for comparisons between the different groups. RESULTS: A total of 662 eligible participants completed the instrument and identified as radiation oncology professionals. In the cGy and Gy NUMi scores, approximately 2% of respondents scored low-average, approximately 40% scored high-average, and approximately 58% scored high, with a median score of 18.0. Although the optimum NUMi score for ASRT members is unknown, one might expect our cohort to have numeracy skills at least as high as college freshmen. Roughly one-sixth of our study group scored at or below the average score of college freshmen (NUMi = 15). In the subset analysis of NUMi questions pertaining to radiation dose unit (cGy vs Gy), respondents performed better with cGy (mean score: 2.94; range, 2-3) versus Gy (mean: 2.91; range, 0-3; P = .011). CONCLUSIONS: In this study of limited sample size, overall numeracy is quite good compared with the general population. However, the range of scores is wide, and some respondents have lower scores that may be concerning, suggesting that numeracy may be an issue that requires improvement for a subset of the studied cohort. Performance was superior with the unit cGy; thus, the adoption of cGy as the standard unit is reasonable.

Genetic characterization of a case of sellar metastasis from bronchial carcinoid neuroendocrine tumor.

BACKGROUND: Metastasis to the pituitary gland from neuroendocrine tumors is a rare occurrence that may originate from primary tumors the lung, gastrointestinal tract, thyroid, and pancreas, among others. Patients may present with signs of endocrine dysfunction secondary to pituitary involvement, as well as mass effect-related symptoms including headaches and visual deficits. Despite a small but accumulating body of literature describing the clinical and histopathological correlates for pituitary metastases from neuroendocrine tumors, the genetic basis underlying this presentation remains poorly characterized. CASE DESCRIPTION: We report the case of a 68-year-old with a history of lung carcinoid tumor who developed a suprasellar lesion, causing mild visual deficits but otherwise without clinical or biochemical endocrine abnormalities. She underwent endoscopic endonasal resection of her tumor with final pathology confirming metastasis from her original neuroendocrine tumor. Whole-exome sequencing was performed on the resected sellar tumor and matching blood, revealing increased genomic instability and key mutations in PTCH1 and BCOR that have been previously implicated in both systemic neuroendocrine and primary pituitary tumors with potentially actionable therapeutic targets. CONCLUSION: This is the first genomic characterization of a metastatic tumor to the sella and reports potential genetic insight, implicating PTCH1 and BCOR mutations, into the pathophysiology of sellar metastasis from primary systemic tumors.

Laser interstitial thermal therapy for treatment of cerebral radiation necrosis.

Radiation necrosis is a well described complication after radiosurgical treatment of intracranial pathologies - best recognized after the treatment of patients with arteriovenous malformations and brain metastases but possibly also affecting patients treated with radiosurgery for meningioma. The pathophysiology of radiation necrosis is still not well understood but is most likely a secondary local tissue inflammatory response to brain tissue injured by radiation. Radiation necrosis in brain metastases patients may present radiographically and behave clinically like recurrent tumor. Differentiation between radiation necrosis and recurrent tumor has been difficult based on radiographic changes alone. Biopsy or craniotomy therefore remains the gold standard method of diagnosis. For symptomatic patients, corticosteroids are first-line therapy, but patients may fail medical management due to intolerance of chronic steroids or persistence of symptoms. In these cases, open surgical resection has been shown to be successful in management of surgically amenable lesions but may be suboptimal in patients with deep-seated lesions or extensive prior cranial surgical history, both carrying high risk for peri-operative morbidity. Laser interstitial thermal therapy has emerged as a viable, alternative surgical option. In addition to allowing access to tissue for diagnosis, thermal treatment of the lesion can also be delivered precisely and accurately under real-time imaging guidance. This review highlights the pertinent studies that have shaped the impetus for use of laser interstitial thermal therapy in the treatment of radiation necrosis, reviewing indications, outcomes, and nuances toward successful application of this technology in patients with suspected radiation necrosis.

Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma.

Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy. Strikingly, despite the variety of treatments, there was persistence of a tumor clone, characterized by a deleterious STAG2 mutation, whose deficiency in preclinical studies can cause aneuploidy and aberrant mitotic progression, but remains understudied in the clinical setting. There was near elimination of an EGFR mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently STAG2 mutated clone, with rare mutations in PTPN11 and BRAF, the latter composed of a novel deleterious mutation previously not reported in pediatric glioblastoma (p.D594G). This was accompanied by a mutation signature shift towards one characterized by increased DNA damage repair defects, consistent with the known underlying STAG2 deficiency. As such, this case represents a novel report following the clinical and genetic progression of a STAG2 mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although STAG2 deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing preclinical data supporting a role for STAG2 mutations in gliomagenesis and resistance to standard therapies.

Laser Interstitial Thermotherapy for Treatment of Symptomatic Peritumoral Edema After Radiosurgery for Meningioma.

BACKGROUND: Symptomatic peritumoral edema (PTE) is a known complication after radiosurgical treatment of meningiomas. Although the edema in most patients can be successfully managed conservatively with corticosteroid therapy or bevacizumab, some medically refractory cases may require surgical resection of the underlying lesion when feasible. Laser interstitial thermotherapy (LITT) continues to gain traction as an effective therapeutic modality for the treatment of radiation necrosis where its biggest impact is through the control of peritumoral edema. CASE DESCRIPTION: A 56-year-old woman with neurofibromatosis 2 presented with a symptomatic, regrowing left frontotemporal lesion that had previously been radiated, then resected with confirmed recurrence of grade I meningioma, and subsequently radiated again for lesion recurrence. Given her history of 2 prior same-side craniotomies, including a complication of wound infection, she was not a candidate for further open surgical resection. Having failed conservative management, she underwent LITT with intraoperative biopsy demonstrating viable grade I meningioma. Postoperatively, she demonstrated radiographic marked, serial reduction of PTE and experienced resolution of her symptoms. CONCLUSIONS: This case demonstrates that LITT may be a viable alternative treatment for patients with meningioma with symptomatic PTE who have failed medical therapy and require surgical intervention.

Targeting DNA repair in gliomas.

PURPOSE OF REVIEW: Gliomas represent a disparate group of malignancies with varying clinical outcomes despite a tremendous amount of time, effort, and resources dedicated to their management and understanding. The most aggressive entity, glioblastoma, has a dismal prognosis with poor local control despite intense local and systemic treatment, including radiation therapy. RECENT FINDINGS: Given the heterogeneity in genotype, phenotype, and patient outcomes, researchers and clinicians have turned their attention toward attacking DNA damage response and repair mechanisms in gliomas in an effort to develop novel chemo and radiosensitizers. However, despite extensive work in both the laboratory and the clinic, no sensitizers have yet to emerge as clear options in the treatment of glioma, often because of meager preclinical data or an inability to penetrate the blood-brain barrier. SUMMARY: This review will examine current understanding of molecular DNA repair targets in glioma and their potential exploitation to improve local control and, ultimately, overall survival of patients afflicted with these diseases.

Defining an Intermediate-risk Group for Low-grade Glioma: A National Cancer Database Analysis.

BACKGROUND: RTOG 9802 identified a cohort of patients with age less than 40 years and undergoing gross total resection as having low-risk, low-grade glioma (LR-LGG). European Organization for Research and Treatment of Cancer studies have demonstrated additional prognostic features in this group. The aim of this study was to analyze clinical factors associated with overall survival (OS), identify a potentially higher risk group within LR-LGG, and investigate patterns of care for adjuvant therapy. MATERIALS AND METHODS: Patients with LR-LGG diagnosed between 2010 to 2013 were identified in the National Cancer Database. Kaplan-Meier method was used to analyze OS. Propensity score matching and multivariate analysis were utilized to adjust for differences in cohorts. RESULTS: A total of 1,032 patients with LR-LGG were identified. Histological breakdown was 42.0% astrocytoma, 33.2% oligodendroglioma, and 25.8% mixed. Median follow-up was 3.9 years; median pre-operative tumor size was 4.0 cm. Overall, 834 (80.8%) underwent observation and 198 (19.2%) received adjuvant therapy. Tumor size >5 cm predicted for receipt of adjuvant therapy on regression analyses (OR=2.02, p=0.001). On multivariate analysis, tumor size >5 cm (hazard ratio=1.95) and non-oligodendroglioma histology (hazard ratio=2.50) were associated with inferior OS (both p<0.05). For patients with both poor prognostic features (a subset we consider "intermediate-risk"), 5-year OS was 78.4%, compared to 94.1% for all other low-risk patients (p<0.001). After propensity score matching, the intermediate-risk group continued to be associated with worse 5-year OS: 80.5% vs. 94.0%, p=0.004. CONCLUSION: Due to inferior OS for patients with LR-LGG with >5 cm, non-oligodendroglioma tumors, we propose an 'intermediate-risk' clinical classification for this subset.

Moderate hypofractionation and stereotactic body radiation therapy in the treatment of prostate cancer.

For prostate cancer radiation therapy, daily sessions spanning approximately 2 months has been considered the standard of care for patients managed with curative intent. In recent years, data has emerged which supports the use of higher dose per fraction schemes leading to a reduced duration of treatment. This form of radiation-generally termed moderate hypofractionation or stereotactic body radiation therapy-increasingly appears to be a safe and effective alternative to the conventional course. This review summarizes salient data from the literature on outcomes, toxicities, and future directions for this innovative strategy of care.

Cutaneous T-Cell Lymphoma: Trends in Radiation Doses and Patterns of Care 2004-2015.

BACKGROUND AND AIM: Radiotherapy is an effective treatment for cutaneous T-cell lymphoma (CTCL). Since 2009, studies have advocated for low-dose radiotherapy (<30 Gy) given it results in similar response rates and less toxicity compared to higher doses (≥30 Gy). We aimed to see if low-dose radiotherapy has been adopted on a national scale in the USA. MATERIALS AND METHODS: A total of 11,292 adult patients with CTCL were identified in the National Cancer Database. Logistic regression models were created to evaluate predictors for use of low-dose radiotherapy. RESULTS: A minority of patients received low-dose radiotherapy (22.4%). The annual percentage of patients receiving low-dose radiotherapy increased from 17.2% in 2009 to 38.4% in 2015. High-volume facilities were associated with use of low-dose radiotherapy (5th quintile vs. bottom two quintiles, odds ratio(OR)=1.76, 95% confidence interval(CI)=1.22-2.54, p=0.003). CONCLUSION: Although the radiotherapy dose administered is decreasing, most patients with CTCL are still receiving doses that may be higher than needed to palliate their disease effectively.