Faculty Bibliography

Purpose: To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. Methods: ASCO convened an Expert Panel and conducted a systematic review of the literature. Results: Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. Recommendations: Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non-small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy.

PURPOSE/OBJECTIVE:Randomized data support accelerated partial breast irradiation (APBI) for early-stage breast cancer with variable techniques and cosmesis outcomes. We have treated patients with 5-fraction prone external beam APBI for over a decade and herein report acute and late outcomes. METHODS AND MATERIALS/METHODS:Patients receiving APBI 600 cGy × 5 between 2010 and 2019 were included. APBI was primarily delivered prone, with opposed tangents targeting the tumor bed expanded by 1.5 cm (cropped 6 mm from skin). Ipsilateral breast was constrained to V50% < 60% and V100% < 35%. Survival was estimated with Kaplan-Meier. Late toxicities and clinician- and patient-rated cosmesis were evaluated for patients with >6 months follow-up (FU). RESULTS:Of 345 patients meeting criteria, 14 were excluded due to APBI given for ipsilateral breast tumor recurrence (IBTR; n = 3), palliation (n = 9), and incomplete radiation therapy course (n = 2). Of the 331 remaining, median age was 70, 7.2% had ductal carcinoma in situ, and 94.3% were treated prone, with 32% treated every other day and 68% on consecutive days. Mean heart dose was 23.8 cGy for left-sided and 12.7 cGy for right-sided cancers. Ipsilateral lung V30% was 0.4%. At 5-year median FU, there were 7 (2.1%) IBTR, 9 (2.7%) contralateral recurrences, and 1 (0.3%) distant metastasis. Five-year local recurrence-free, disease-free, and overall survival was 99.5%, 96.7%, and 98.1%, respectively. When comparing patients with IBTR versus without, a higher proportion did not receive hormone therapy (71.4% vs. 26.2%, P = .018). Rates of acute grade 1 to 2 dermatitis, fatigue, and pain were 35.4%, 21.8%, and 9.4%, respectively, with no grade 3 toxicity. The rate of good-excellent physician- and patient-rated cosmesis (n = 199, median FU 2.8 years) was 92.5% and 89.4%, respectively. Patients experienced low rates of telangiectasia, fibrosis, and retraction/atrophy. CONCLUSIONS:We report excellent dosimetric, oncologic, cosmetic, and late toxicity outcomes for patients treated with 5-fraction APBI. To our knowledge this is the largest series of women treated with prone APBI.

BACKGROUND:Hypofractionation has historically been underutilized among breast cancer patients with connective tissue diseases given a theoretical risk for increased toxicity and their overall underrepresentation in clinical trials that established hypofractionation as standard of care. We aim to compare the rates of toxicity in patients with autoimmune connective tissue diseases treated with conventionally fractioned radiation therapy (CF-RT) and hypofractionated RT (HF-RT) including accelerated partial breast irradiation. MATERIALS AND METHODS/METHODS:1,983 patients treated with breast conservation between 2012 and 2016 were reviewed for diagnosis of autoimmune disease. Univariate analysis using binary logistic regression was performed to evaluate the effect of disease and treatment variables on acute and late toxicity. Multivariate analyses using Cox regression models were used to evaluate the independent associations between covariates and the primary endpoints. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated for reach risk group. RESULTS:92 patients with autoimmune disease were identified. Median follow-up was 59 months. 35% of patients received CF-RT and 65% of patients received hypofractionated RT (HF-RT), of which 70% received whole breast radiation (WBI) without regional nodal irradiation (RNI), 12% received WBI with RNI, and 18% received accelerated partial breast radiation. Patients who received CF-RT were significantly more likely to have AD symptoms (78% vs 37%, p<0.001), to be managed on DMARDs (41% vs 15%, p=0.013) and to have active autoimmune disease (84% vs 43%, p<0.001). On multivariate analysis, HF-RT was associated with a significantly decreased odds of acute and late grade 2/3 toxicity compared to CF-RT fractionation (acute: OR 0.200 95% CI 0.064-0.622, p=0.005; late: OR 0.127 95% CI 0.031 - 0.546, p=0.005). CONCLUSION/CONCLUSIONS:Hypofractionation including APBI is associated with less acute or late grade 2/3 toxicity in this population.

Therapeutic advances for glioblastoma have been minimal over the past 2 decades. In light of the multitude of recent phase III trials that have failed to meet their primary endpoints following promising preclinical and early-phase programs, a Society for Neuro-Oncology Think Tank was held in November 2020 to prioritize areas for improvement in the conduct of glioblastoma clinical trials. Here, we review the literature, identify challenges related to clinical trial eligibility criteria and trial design in glioblastoma, and provide recommendations from the Think Tank. In addition, we provide a data-driven context with which to frame this discussion by analyzing key study design features of adult glioblastoma clinical trials listed on ClinicalTrials.gov as "recruiting" or "not yet recruiting" as of February 2021.

Radiation therapy has long been a critical modality of treatment of patients with central nervous system tumors, including primary brain tumors, brain metastases, and meningiomas. Advances in radiation technology and delivery have allowed for more precise treatment to optimize patient outcomes and minimize toxicities. Improved understanding of the molecular underpinnings of brain tumors and normal brain tissue response to radiation will allow for continued refinement of radiation treatment approaches to improve clinical outcomes for brain tumor patients. With continued advances in precision and delivery, radiation therapy will continue to be an important modality to achieve optimal outcomes of brain tumor patients.

PURPOSE/OBJECTIVE:Detector arrays and profile-scans have widely replaced film-measurements for quality assurance (QA) on linear accelerators. Film is still used for relative output factor (ROF) measurements, positioning, and dose-profile verification for annual Leksell Gamma Knife (LGK) QA. This study shows that small-field active detector measurements can be performed in the easily accessed clinical mode and that they are an effective replacement to time-consuming and exacting film measurements. METHODS:Beam profiles and positioning scans for 4-mm, 8-mm, and 16-mm-collimated fields were collected along the x-, y-, and z-axes. The Exradin W2-scintillator and the PTW microdiamond-detector were placed in custom inserts centered in the Elekta solid-water phantom for these scans. GafChromic EBT3-film was irradiated with single uniformly collimated exposures as the clinical-standard reference, using the same solid-water phantom for profile tests and the Elekta film holder for radiation focal point (RFP)/patient-positioning system (PPS) coincidence. All experimental data were compared to the tissue-maximum-ratio-based (TMR10) dose calculation. RESULTS:The detector-measured beam profiles and film-based profiles showed excellent agreement with TMR10-predicted full-width, half-maximum (FWHM) values. Absolute differences between the measured FWHM and FWHM from the treatment-planning system were on average 0.13 mm, 0.08 mm, and 0.04 mm for film, microdiamond, and scintillator, respectively. The coincidence between the RFP and the PPS was measured to be ≤0.5 mm with microdiamond, ≤0.41 mm with the W2-1 × 1 scintillator, and ≤0.22 mm using the film-technique. CONCLUSIONS:Small-volume field detectors, used in conjunction with a clinically available phantom, an electrometer with data-logging, and treatment plans created in clinical mode offer an efficient and viable alternative for film-based profile tests. Position verification can be accurately performed when CBCT-imaging is available to correct for residual detector-position uncertainty. Scans are easily set up within the treatment-planning-system and, when coupled with an automated analysis, can provide accurate measurements within minutes.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Non-squamous cell carcinoma (SCC) malignancies are rare, but well described laryngeal pathologies. However, the epidemiology and clinical behavior of these tumors is not well studied. STUDY DESIGN/METHODS:Retrospective cohort study. METHODS:Patients diagnosed with non-squamous cell larynx cancer from 2004 to 2017 in the National Cancer Database were selected. Demographic, clinicopathologic factors, treatments, and survival were analyzed. Univariable and multivariable cox regression were performed. Survival was compared with a propensity score-matched (PSM) population of laryngeal SCC patients. RESULTS:A total of 136,235 cases of larynx cancer were identified. After excluding SCC variants, 2,172 (1.6%) patients met inclusion criteria. The most common histology was chondrosarcoma (374, 17.2%), followed by small cell (345, 15.9%), and spindle cell carcinoma (268, 12.3%). The most common treatment was surgery (683, 31.4%) followed by chemoradiation (409, 18.8%) and surgery and adjuvant radiation (288, 13.3%). Overall, 3- and 5-year survival was 67.9% and 59.4%, respectively. In multivariate analysis controlling for age, stage, comorbidity, histology, and treatment modality; chondrosarcoma had the best survival (hazard ratio [HR] 0.11, confidence interval [CI] 0.07-0.19, P < .001). In a PSM population, matched for age, stage, comorbidity, and treatments; non-SCC patients had significantly lower survival (51.5% vs. 59.9%, P < .001). CONCLUSION/CONCLUSIONS:A diverse range of non-squamous cell malignancies occur in the larynx. In general, these tumors have poor survival, with few exceptions such as chondrosarcoma. While the majority of these histologies undergo surgical-based treatments in other sites, only 53% of patients underwent surgical-based treatment in the larynx. These data could guide clinicians in determining the outcome of treatment in these patients. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2022.

PURPOSE/OBJECTIVE:The omission of radiation therapy (RT) in elderly women with stage 1 estrogen-receptor positive (ER+) breast cancer receiving endocrine therapy (ET) is an acceptable strategy based on randomized trial data. Less is known about the omission of ET +/- RT. PATIENT AND METHODS/METHODS:We analyzed SEER-Medicare data for 13,321 women ≥ 66 years with stage I ER+ breast cancer from 2007-2012 who underwent breast conserving surgery. Patients were classified into 4 groups: 1) ET+RT (reference) 2) ET alone (ET), 3) RT alone (RT) and 4) neither RT nor ET (NT). Second breast cancer events (SBCE) were captured using Chubak's high-specificity algorithm. We used Chi-square tests for descriptive statistics, multivariable multinomial logistic regression to estimate relative risks (RR) of undergoing a treatment, and multivariable, propensity-weighted competing-risks survival regression to estimate standardized hazard ratio (SHR) of SBCE. We set significance at p≤0.01. RESULTS:Most women underwent both treatments, with 44% undergoing ET+RT, 41% RT, 6.6% ET, and 8.6% NT but practice patterns varied over time: from 2007-2012, RT decreased from 49% to 30%, whereas ET and ET+RT increased (ET: 5.4% to 9.6%; ET+RT: 38% to 51%). Compared to patients 66-69 years, patients 80-85 years were more likely to receive NT (OR=8.9), RT (OR=1.9), or ET (OR=8.8) vs. ET+RT (p<0.01).3% of subjects had an SBCE (2.2% ET+RT, 3.0% RT, 3.2% ET, 7.0% NT). Relative to ET+RT, NT and ET were associated with higher SBCE (NT: SHR 3.7, p<0.001; ET: SHR 2.2, p=0.008)), whereas RT was not associated with a higher SBCE (SHR 1.21, p=0.137). Clinical factors associated with higher SBCE were HER2 positivity and pT1c (SHR 1.7, p=0.006). CONCLUSIONS:Treatment with RT alone in older women with stage I ER+ disease is decreasing. RT alone is not associated with an increased risk for SBCE. By contrast, NT and ET are both associated with higher SBCE in multivariable analysis with propensity weighting. Further study of the omission of endocrine therapy in this patient population is warranted.