Development and validation of a recursive partitioning analysis-based pretreatment decision-making tool identifying ideal candidates for spine stereotactic body radiation therapy.

BACKGROUND: This study was aimed at developing and validating a decision-making tool predictive of overall survival (OS) for patients receiving stereotactic body radiation therapy (SBRT) for spinal metastases. METHODS: Three hundred sixty-one patients at one institution were used for the training set, and 182 at a second institution were used for external validation. Treatments most commonly involved one or three fractions of spine SBRT. Exclusion criteria included proton therapy and benign histologies. RESULTS: The final model consisted of the following variables and scores: Spinal Instability Neoplastic Score (SINS) ≥ 6 (1), time from primary diagnosis < 21 months (1), Eastern Cooperative Oncology Group (ECOG) performance status = 1 (1) or ECOG performance status > 1 (2), and >1 organ system involved (1). Each variable was an independent predictor of OS (p < .001), and each 1-point increase in the score was associated with a hazard ratio of 2.01 (95% confidence interval [CI], 1.79-2.25; p < .0001). The concordance value was 0.75 (95% CI, 0.71-0.78). The scores were discretized into three groups-favorable (score = 0-1), intermediate (score = 2), and poor survival (score = 3-5)-with 2-year OS rates of 84% (95% CI, 79%-90%), 46% (95% CI, 36%-59%), and 21% (95% CI, 14%-32%), respectively (p < .0001 for each). In the external validation set (182 patients), the score was also predictive of OS (p < .0001). Increasing SINS was predictive of decreased OS as a continuous variable (p < .0001). CONCLUSIONS: This novel score is proposed as a decision-making tool to help to optimize patient selection for spine SBRT. SINS may be an independent predictor of OS.

Feasibility and oncologic control after percutaneous image guided ablation of metastatic renal cell carcinoma.

PURPOSE: We assessed the safety, local control and oncologic efficacy of percutaneous ablation in the treatment of metastatic renal cell carcinoma. MATERIALS AND METHODS: A retrospective review was performed of 61 patients who underwent 74 ablation procedures to treat 82 metastatic renal cell carcinoma lesions with the intent of local eradication. Technical success, local tumor control, complications and patient survival were analyzed according to standard criteria. RESULTS: Four (4.9%) technical failures were observed while 2 patients were lost to followup. Time to recurrence was assessed for the subset of 76 (93%) tumors that were followed after ablation. Six (of 76, 7.9%) tumors recurred at a mean of 1.6 years after ablation (median 1.4, range 0.6 to 2.9). Thus, known overall local tumor control was achieved in 70 of 80 (87.5%) tumors. Estimated local recurrence-free survival rates (95% CI, number still at risk) at 1, 2 and 3 years after ablation were 94% (88-100, 41), 94% (88-100, 32) and 83% (70-97, 17), respectively. Estimated overall survival rates (95% CI, number still at risk) at 1, 2 and 3 years after ablation were 87% (79-97, 42), 83% (73-94, 31) and 76% (63-90, 19), respectively. CONCLUSIONS: Image guided ablation of metastatic renal cell carcinoma is a relatively safe procedure with acceptable local control rates. Ablation may offer patients a minimally invasive option of local tumor eradication and warrants a role in the multimodal treatment approach for select patients.

Cryoablation of sternal metastases for pain palliation and local tumor control.

PURPOSE: To determine safety and effectiveness of cryoablation of sternal metastases for pain palliation and local tumor control. MATERIALS AND METHODS: A tumor ablation database was retrospectively reviewed for sternal cryoablation procedures performed between January 2005 and June 2013, which yielded 15 procedures to treat 12 sternal metastases in 12 patients (five men). Median patient age was 57 years (range, 38-80 y). Metastases arose from five primary sites (breast, lung, kidney, ampulla, and thyroid), and median tumor size was 3.8 cm (range, 2.2-7.5 cm). Seven patients (58%) underwent cryoablation for pain palliation, and five (42%) underwent cryoablation for local tumor control of oligometastatic disease. Clinical outcomes (including complications, local tumor control, and pain response) were evaluated retrospectively. RESULTS: Mean pain scores decreased from 7.0 ± 1.9 (median, 7; range, 4-10) at baseline to 1.8 ± 1.2 (median, 1.5; range, 0-4) following cryoablation (P = .00049). Two patients had durable pain palliation, and four had greater than 1 month of pain relief, with a median duration of 5.7 months (range, 1.5-14.7 mo). Two patients in whom recurrent pain developed underwent repeat cryoablation, with durable pain relief. Allowing for a single repeat treatment, local tumor control was achieved in four of five patients (80%) treated for this indication, with median follow-up of 8.4 months (range, 2.6-13.6 mo). In one patient (8%), an infectious complication developed that was successfully treated with antibiotics on an outpatient basis. CONCLUSIONS: Cryoablation is a safe and potentially effective treatment for patients with painful sternal metastases and can achieve local tumor control in select patients.

Lung tumor motion change during stereotactic body radiotherapy (SBRT): an evaluation using MRI.

The purpose of this study is to investigate changes in lung tumor internal target volume during stereotactic body radiotherapy treatment (SBRT) using magnetic resonance imaging (MRI). Ten lung cancer patients (13 tumors) undergoing SBRT (48 Gy over four consecutive days) were evaluated. Each patient underwent three lung MRI evaluations: before SBRT (MRI-1), after fraction 3 of SBRT (MRI-3), and three months after completion of SBRT (MRI-3m). Each MRI consisted of T1-weighted images in axial plane through the entire lung. A cone-beam CT (CBCT) was taken before each fraction. On MRI and CBCT taken before fractions 1 and 3, gross tumor volume (GTV) was contoured and differences between the two volumes were compared. Median tumor size on CBCT before fractions1 (CBCT-1) and 3 (CBCT-3) was 8.68 and 11.10 cm3, respectively. In 12 tumors, the GTV was larger on CBCT-3 compared to CBCT-1 (median enlargement, 1.56 cm3). Median tumor size on MRI-1, MRI-3, and MRI-3m was 7.91, 11.60, and 3.33 cm3, respectively. In all patients, the GTV was larger on MRI-3 compared to MRI-1 (median enlargement, 1.54 cm3). In all patients, GTV was smaller on MRI-3m compared to MRI-1 (median shrinkage, 5.44 cm3). On CBCT and MRI, all patients showed enlargement of the GTV during the treatment week of SBRT, except for one patient who showed minimal shrinkage (0.86 cm3). Changes in tumor volume are unpredictable; therefore, motion and breathing must be taken into account during treatment planning, and image-guided methods should be used, when treating with large fraction sizes.

Influence of patient's physiologic factors and immobilization choice with stereotactic body radiotherapy for upper lung tumors.

The purpose of the present study was to compare the impact of pulmonary function, body habitus, and stereotactic body radiation therapy (SBRT) immobilization on setup and reproducibility for upper lung tumor. From 2008 through 2011, our institution's prospective SBRT database was searched for patients with upper lung tumors. Two SBRT immobilization strategies were used: full-length BodyFIX and thermoplastic S-frame. At simulation, free-breathing, four-dimensional computed tomography was performed. For each treatment, patients were set up to isocenter with in-room lasers and skin tattoos. Shifts from initial and subsequent couch positions with cone-beam computed tomography (CBCT) were analyzed. Accounting for setup uncertainties, institutional tolerance of CBCT-based shifts for treatment was 2, 2, and 4 mm in left-right, anterior-posterior, and cranial-caudal directions, respectively; shifts exceeding these limits required reimaging. Each patient's pretreatment pulmonary function test was recorded. A multistep, multivariate linear regression model was performed to elucidate intervariable dependency for three-dimensional calculated couch shift parameters. BodyFIX was applied to 76 tumors and S-frame to 17 tumors. Of these tumors, 41 were non-small cell lung cancer and 15 were metastatic from other sites. Lesions measured < 1 (15%), 1.1 to 2 (50%), 2.1 to 3 (25%), and > 3 (11%) cm. Errors from first shifts of first fractions were significantly less with S-frame than BodyFIX (p < 0.001). No difference in local control (LC) was found between S-frame and BodyFIX (p = 0.35); two-year LC rate was 94%. Multivariate modeling confirmed that the ratio of forced expiratory volume in the first second of expiration to forced vital capacity, body habitus, and the immobilization device significantly impacted couch shift errors. For upper lung tumors, initial setup was more consistent with S-frame than BodyFIX, resulting in fewer CBCT scans. Patients with obese habitus and poor lung function had more SBRT setup uncertainty; however, outcome and probability for LC remained excellent.

Assessment of minimum target dose as a predictor of local failure after spine SBRT.

OBJECTIVES: Metastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. METHODS: Spine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20-24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27-36 Gy and 21-24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. RESULTS: 522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3-54.4). The cumulative incidence of local failure was 10.5 % (7.4-13.4) at 1 year and 16.3 % (12.6-19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 - 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6-9.4) vs. 14.2 % (8.3-19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). CONCLUSIONS: Spine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14-15.3 Gy with single fraction SBRT is recommended whenever possible.

Sublobar Resection, Stereotactic Body Radiation Therapy, and Percutaneous Ablation Provide Comparable Outcomes for Lung Metastasis-Directed Therapy.

BACKGROUND: Prolonged survival of patients with metastatic disease has furthered interest in metastasis-directed therapy (MDT). RESEARCH QUESTION: There is a paucity of data comparing lung MDT modalities. Do outcomes among sublobar resection (SLR), stereotactic body radiation therapy (SBRT), and percutaneous ablation (PA) for lung metastases vary in terms of local control and survival? STUDY DESIGN AND METHODS: Medical records of patients undergoing lung MDT at a single cancer center between January 2015 and December 2020 were reviewed. Overall survival, local progression, and toxicity outcomes were collected. Patient and lesion characteristics were used to generate multivariable models with propensity weighted analysis. RESULTS: Lung MDT courses (644 total: 243 SLR, 274 SBRT, 127 PA) delivered to 511 patients were included with a median follow-up of 22 months. There were 47 local progression events in 45 patients, and 159 patients died. Two-year overall survival and local progression were 80.3% and 63.3%, 83.8% and 9.6%, and 4.1% and 11.7% for SLR, SBRT, and PA, respectively. Lesion size per 1 cm was associated with worse overall survival (hazard ratio, 1.24; P = .003) and LP (hazard ratio, 1.50; P < .001). There was no difference in overall survival by modality. Relative to SLR, there was no difference in risk of local progression with PA; however, SBRT was associated with a decreased risk (hazard ratio, 0.26; P = .023). Rates of severe toxicity were low (2.1%-2.6%) and not different among groups. INTERPRETATION: This study performs a propensity weighted analysis of SLR, SBRT, and PA and shows no impact of lung MDT modality on overall survival. Given excellent local control across MDT options, a multidisciplinary approach is beneficial for patient triage and longitudinal management.

Development and validation of a unifying pre-treatment decision tool for intracranial and extracranial metastasis-directed radiotherapy.

Background: Though metastasis-directed therapy (MDT) has the potential to improve overall survival (OS), appropriate patient selection remains challenging. We aimed to develop a model predictive of OS to refine patient selection for clinical trials and MDT. Patients and methods: We assembled a multi-institutional cohort of patients treated with MDT (stereotactic body radiation therapy, radiosurgery, and whole brain radiation therapy). Candidate variables for recursive partitioning analysis were selected per prior studies: ECOG performance status, time from primary diagnosis, number of additional non-target organ systems involved (NOS), and intracranial metastases. Results: A database of 1,362 patients was assembled with 424 intracranial, 352 lung, and 607 spinal treatments (n=1,383). Treatments were split into training (TC) (70%, n=968) and internal validation (IVC) (30%, n=415) cohorts. The TC had median ECOG of 0 (interquartile range [IQR]: 0-1), NOS of 1 (IQR: 0-1), and OS of 18 months (IQR: 7-35). The resulting model components and weights were: ECOG = 0, 1, and > 1 (0, 1, and 2); 0, 1, and > 1 NOS (0, 1, and 2); and intracranial target (2), with lower scores indicating more favorable OS. The model demonstrated high concordance in the TC (0.72) and IVC (0.72). The score also demonstrated high concordance for each target site (spine, brain, and lung). Conclusion: This pre-treatment decision tool represents a unifying model for both intracranial and extracranial disease and identifies patients with the longest survival after MDT who may benefit most from aggressive local therapy. Carefully selected patients may benefit from MDT even in the presence of intracranial disease, and this model may help guide patient selection for MDT.

Thoracic Radiotherapy for Renal Cell Carcinoma Metastases: Local Control for the Management of Lung and Mediastinal Disease in the Modern Era.

INTRODUCTION/BACKGROUND: Radiotherapy (RT) is an alternative local therapy to metastasectomy in the treatment of thoracic metastases from renal cell carcinoma (RCC), including the management of life-threatening disease. PATIENTS AND METHODS: We reviewed patients with lung and mediastinal RCC metastases treated with RT at our institution. Overall survival (OS) and metastasis control (MC) was measured from the start of RT using the Kaplan-Meier (KM) method. RESULTS: Seventy-one patients were treated with RT for 89 lung (n = 58) or mediastinal (n = 31) metastases. Of 89 treated lesions, 11 (12%) had local tumor recurrence, at a median of 1.6 years (range 0.4-2.9). MC at 1, 3, and 5-years was 96.6%, 83.5%, and 67.9%, respectively. For the 58-lung metastasis-directed RT courses, MC rates at 1, 3, and 5-years were 95.0%, 84.5%, and 84.5%, respectively (median MC not reached). For the 31-mediastinum metastasis-directed RT courses, MC rates at 1, 3, and 5-years were 100%, 43.4%, and 43.4%, respectively (median MC 2.9 years). MC was significantly improved for lung lesions compared to mediastinal lesions (P = .046). OS for the entire cohort at 1, 3, and 5 years was 65.2%, 48.5%, and 38.0%. There was no difference in OS based on metastatic sites in the 71 patients. Nineteen patients received RT to 19 lesions with the intention of preventing an event such as airway compromise or vascular invasion. One and two-year MC for these 19 lesions were 88.9% and 71.1%, respectively (median local control 2.4 years). OS in these 19 patients at 1, 2, and 5 years were 62.1%, 48.3%, and 32.2% respectively, with median survival 1.2 years. No patients developed grade 4 or 5 acute or late toxicities. CONCLUSION: Radiation therapy can safely achieve high metastasis control rates for lung and mediastinal metastases from RCC, including lesions at high risk for causing a life-threatening event.

CD117, BAP1, MTAP, and TdT Is a Useful Immunohistochemical Panel to Distinguish Thymoma from Thymic Carcinoma.

BACKGROUND: The morphologic distinction between thymic carcinomas and thymomas, specifically types B3, A, and occasionally micronodular thymomas with lymphoid stroma (MNTLS) can be challenging, as has also been shown in interobserver reproducibility studies. Since thymic carcinomas have a worse prognosis than thymomas, the diagnosis is important for patient management and treatment. This study aimed to identify a panel of immunohistochemical (IHC) markers that aid in the distinction between thymomas and thymic carcinomas in routine practice. MATERIALS AND METHOD: Thymic carcinomas, type A and B3 thymomas, and MNTLS were identified in an institutional database of thymic epithelial tumors (TET) (1963-2021). IHC was performed using antibodies against TdT, Glut-1, CD5, CD117, BAP1, and mTAP. Percent tumor cell staining was recorded (Glut-1, CD5, CD117); loss of expression (BAP1, mTAP) was considered if essentially all tumor cells were negative; TdT was recorded as thymocytes present or absent (including rare thymocytes). RESULTS: 81 specimens included 44 thymomas (25 type A, 11 type B3, 8 MNTLS) and 37 thymic carcinomas (including 24 squamous cell carcinomas). Using BAP1, mTAP, CD117 (cut-off, 10%), and TdT, 88.9% of thymic carcinomas (95.7% of squamous cell carcinomas) and 77.8% of thymomas could be predicted. Glut-1 expression was not found to be useful in that distinction. All tumors that expressed CD5 in ≥50% of tumor cells also expressed CD117 in ≥10% of tumor cells. In four carcinomas with homozygous deletion of CDKN2A, mTAP expression was lost in two squamous cell carcinomas and in a subset of tumor cells of an adenocarcinoma and was preserved in a lymphoepithelial carcinoma. CONCLUSION: A panel of immunostains including BAP1, mTAP, CD117 (using a cut-off of 10% tumor cell expression), and TdT can be useful in the distinction between thymomas and thymic carcinomas, with only a minority of cases being inconclusive.

Integrating a Grassroots Well-Being Curriculum into a Radiation Oncology Residency Program.

PURPOSE: The burnout rate among US radiation oncology residents was 33% in 2016. To our knowledge there are no published interventions addressing burnout among radiation oncology residents. We describe the implementation of a well-being curriculum, cocreated by a psychologist, a medical humanities professional, and radiation oncology attending and resident physicians. METHODS AND MATERIALS: Radiation oncology residents at our institution were surveyed to determine themes that induced burnout. A curriculum was developed, with monthly small group sessions focused on 1 identified topic. Sessions alternated between psychological tool-focused approaches and humanities exercises. These were led by a psychologist or medical humanities professional. Residents were given protected time to attend sessions during business hours. Participation was optional. Participants were assigned a random identifier, and the Stanford Professional Fulfillment Index (PFI) was assessed at baseline and 3-month intervals. PFI trends were analyzed after 1 year. At the end of the year, a focus group was held to evaluate work satisfaction and self-reported interactions with patients and coworkers. This information was used to improve the curriculum. RESULTS: All 12 residents in the radiation oncology program participated in the curriculum. There was an equal number of residents of postgraduate years 2 through 5. Six of the participants were female. Of the participants, 11 completed the PFI. At baseline, 80% of residents met criteria for burnout. This decreased to 67%, 50%, and 33% at 3, 6, and 9 months, respectively. The proportion of residents meeting criteria for very good professional fulfillment was 30%, 56%, 38%, and 22% at baseline and 3, 6, and 9 months, respectively. On average, 9 of 12 residents attended each session. CONCLUSIONS: Our experience demonstrates the feasibility of collaborating with residents in the development of a well-being curriculum to cater programming to their needs, which we believe led to excellent engagement and attendance at each session.

Stereotactic Body Radiation Therapy for Metastases in Long Bones.

PURPOSE: To evaluate the cumulative incidence of fracture and local failure and associated risk factors after stereotactic body radiation therapy (SBRT) for long bone metastases. METHODS AND MATERIALS: Data from 111 patients with 114 metastases in the femur, humerus, and tibia treated with SBRT in 7 international centers between October 2011 and February 2021 were retrospectively reviewed and analyzed using a competing risk regression model. RESULTS: The median follow-up was 21 months (range, 6-91 months). All but 1 patient had a Karnofsky performance status ≥70. There were 84 femur (73.7%), 26 humerus (22.8%), and 4 tibia (3.5%) metastases from prostate (45 [39.5%]), breast (22 [19.3%]), lung (15 [13.2%]), kidney (13 [11.4%]), and other (19 [16.6%]) malignancies. Oligometastases accounted for 74.8% of metastases and 28.1% were osteolytic. The most common total doses were 30 to 50 Gy in 5 daily fractions (50.9%). Eight fractures (5 in the femur, 2 in the tibia, and 1 in the humerus) were observed with a median time to fracture of 12 months (range, 0.8-33 months). In 6 out of 8 patients, fracture was not associated with local failure. The cumulative incidence of fracture was 3.5%, 6.1%, and 9.8% at 1, 2, and 3 years, respectively. The cumulative incidence of local failure (9/110 metastases with imaging follow-up) was 5.7%, 7.2%, and 13.5% at 1, 2, and 3 years, respectively. On multivariate analysis, extraosseous disease extension was significantly associated with fracture (P = .001; subhazard ratio, 10.8; 95% confidence interval, 2.8-41.9) and local failure (P = .02; subhazard ratio, 7.9; 95% confidence interval, 1.4-44.7). CONCLUSIONS: SBRT for metastases in long bones achieved high rates of durable local metastasis control without an increased risk of fracture. Similar to spine SBRT, patients with extraosseous disease extension are at higher risk of local failure and fracture.

Development and Internal Validation of a Recursive Partitioning Analysis-Based Model Predictive of Pain Flare Incidence After Spine Stereotactic Body Radiation Therapy.

PURPOSE: Pain flares are a common acute toxic effect after stereotactic body radiation therapy (SBRT) for spine metastasis. We aimed to identify a subset of patients with the highest rate of pain flare after spine SBRT to optimize prophylactic corticosteroid administration. METHODS AND MATERIALS: The data set included 428 patients with 610 treatments. We defined pain flare as acute worsening of pain at the treatment site requiring new or higher dose therapy with corticosteroids, opiates, and/or hospitalization. Data were split into 70% training and 30% validation sets using a random number generator. After feature importance testing and generation of a correlation heatmap, feature extraction was performed via recursive partitioning analysis. RESULTS: We identified 125 total pain flares (20%). Five variables met significance (P < .02) for model inclusion: renal primary, soft tissue involvement, Bilsky >0, spinal instability neoplastic score >6, and gross tumor volume >8 cc. One point was assigned for each variable. The low-risk group (score = 0, n = 159) had pain flare rates of 7.0% and 13.6% in the training and validation sets; the intermediate-risk group (score = 1, n = 150) had rates of 14.0% and 16.3%; and the high-risk group (score >1, n = 301) had rates of 28.8% and 31.3%. Patients in the high-risk group had higher rates of flare (odds ratio, 3.50; 95% confidence interval, 2.06-5.92) and accumulated health care costs 3 and 6 months post-SBRT, relative to intermediate- and low-risk patients (P < .001). CONCLUSIONS: Our internally validated model identifies a high-risk group of patients more likely to develop a pain flare after spine SBRT, for whom prophylactic steroids may be considered. Evaluation in a clinical trial is warranted.

Cardiopulmonary Toxicity Following Intensity-Modulated Proton Therapy (IMPT) Versus Intensity-Modulated Radiation Therapy (IMRT) for Stage III Non-Small Cell Lung Cancer.

INTRODUCTION: Intensity-modulated proton therapy (IMPT) has the potential to reduce radiation dose to normal organs when compared to intensity-modulated radiation therapy (IMRT). We hypothesized that IMPT is associated with a reduced rate of cardiopulmonary toxicities in patients with Stage III NSCLC when compared with IMRT. METHODS: We analyzed 163 consecutively treated patients with biopsy-proven, stage III NSCLC who received IMPT (n = 35, 21%) or IMRT (n = 128, 79%). Patient, tumor, and treatment characteristics were analyzed. Overall survival (OS), freedom-from distant metastasis (FFDM), freedom-from locoregional relapse (FFLR), and cardiopulmonary toxicities (CTCAE v5.0) were calculated using the Kaplan-Meier estimate. Univariate cox regressions were conducted for the final model. RESULTS: Median follow-up of surviving patients was 25.5 (range, 4.6-58.1) months. Median RT dose was 60 (range, 45-72) Gy [RBE]. OS, FFDM, and FFLR were not different based on RT modality. IMPT provided significant dosimetric pulmonary and cardiac sparing when compared to IMRT. IMPT was associated with a reduced rate of grade more than or equal to 3 pneumonitis (HR 0.25, P = .04) and grade more than or equal to 3 cardiac events (HR 0.33, P = .08). Pre-treatment predicted diffusing capacity for carbon monoxide less than equal to 57% (HR 2.8, P = .04) and forced expiratory volume in the first second less than equal to 61% (HR 3.1, P = .03) were associated with an increased rate of grade more than or equal to 3 pneumonitis. CONCLUSIONS: IMPT is associated with a reduced risk of clinically significant pneumonitis and cardiac events when compared with IMRT without compromising tumor control in stage III NSCLC. IMPT may provide a safer treatment option, particularly for high-risk patients with poor pretreatment pulmonary function.

Dosimetric predictors of pneumonitis in locally advanced non-small cell lung cancer patients treated with chemoradiation followed by durvalumab.

OBJECTIVES: The incidence and predictors of pneumonitis for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) in the era of consolidation durvalumab have yet to be fully elucidated. In this large single institution analysis, we report the incidence of and factors associated with grade 2 + pneumonitis in NSCLC patients treated with the PACIFIC regimen. MATERIALS AND METHODS: We identified all patients treated at our institution with definitive CRT followed by durvalumab from 2018 to 2021. Clinical documentation and imaging studies were reviewed to determine grade 2 + pneumonitis events, which required the following: 1) pulmonary symptoms warranting prolonged steroid taper, oxygen dependence, and/or hospital admission and 2) radiographic findings consistent with pneumonitis. RESULTS: One-hundred ninety patients were included. The majority received 60 Gray (Gy) in 30 fractions with concurrent carboplatin and paclitaxel. Median number of durvalumab cycles received was 12 (IQR: 4-22). At a median follow-up of 14.8 months, 50 (26.3%) patients experienced grade 2 + pneumonitis with a 1-year cumulative incidence of 27.8% (95% CI: 21.9-35.4). Seventeen (8.9%) patients experienced grade 3 + pneumonitis and 4 grade 5 (2.1%). Dosimetric predictors of pneumonitis included ipsilateral and total lung volume receiving 5 Gy or greater (V5Gy), V10Gy, V20Gy, V40Gy, and mean dose and contralateral V40Gy. Heart V5Gy, V10Gy, and mean dose were also significant variables. Overall survival estimates at 1 and 3 years were 87.4% (95% CI: 82.4-92.8) and 60.3% (95% CI: 47.9-74.4), respectively. CONCLUSION: We report a risk of pneumonitis higher than that seen on RTOG 0617 and comparable to the PACIFIC study. Multiple lung and heart dosimetric factors were predictive of pneumonitis.

Development and Assessment of a Predictive Score for Vertebral Compression Fracture After Stereotactic Body Radiation Therapy for Spinal Metastases.

IMPORTANCE: Vertebral compression fracture (VCF) is a potential adverse effect following treatment with stereotactic body radiation therapy (SBRT) for spinal metastases. OBJECTIVE: To develop and assess a risk stratification model for VCF after SBRT. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study conducted at a high-volume referral center included 331 patients who had undergone 464 spine SBRT treatments from December 2007 through October 2019. Data analysis was conducted from November 1, 2020, to August 17, 2021. Exclusions included proton therapy, prior surgical intervention, vertebroplasty, or missing data. EXPOSURES: One and 3 fraction spine SBRT treatments were most commonly delivered. Single-fraction treatments generally involved prescribed doses of 16 to 24 Gy (median, 20 Gy; range, 16-30 Gy) to gross disease compared with multifraction treatment that delivered a median of 30 Gy (range, 21-50 Gy). MAIN OUTCOMES AND MEASURES: The VCF and radiography components of the spinal instability neoplastic score were determined by a radiologist. Recursive partitioning analysis was conducted using separate training (70%), internal validation (15%), and test (15%) sets. The log-rank test was the criterion for node splitting. RESULTS: Of the 331 participants, 88 were women (27%), and the mean (IQR) age was 63 (59-72) years. With a median follow-up of 21 months (IQR, 11-39 months), we identified 84 VCFs (18%), including 65 (77%) de novo and 19 (23%) progressive fractures. There was a median of 9 months (IQR, 3-21 months) to developing a VCF. From 15 candidate variables, 6 were identified using the backward selection method, feature importance testing, and a correlation heatmap. Four were selected via recursive partitioning analysis: epidural tumor extension, lumbar location, gross tumor volume of more than 10 cc, and a spinal instability neoplastic score of more than 6. One point was assigned to each variable, and the resulting multivariable Cox model had a concordance of 0.760. The hazard ratio per 1-point increase for VCF was 1.93 (95% CI, 1.62-2.30; P < .001). The cumulative incidence of VCF at 2 years (with death as a competing risk) was 6.7% (95% CI, 4.2%-10.7%) for low-risk (score, 0-1; 273 [58.3%]), 17.0% (95% CI, 10.8%-26.7%) for intermediate-risk (score, 2; 99 [21.3%]), and 35.4% (95% CI, 26.7%-46.9%) for high-risk cases (score, 3-4; 92 [19.8%]) (P < .001). Similar results were observed for freedom from VCF using stratification. CONCLUSIONS AND RELEVANCE: The results of this cohort study identify a subgroup of patients with high risk for VCF following treatment with SBRT who may potentially benefit from undergoing prophylactic spinal stabilization or vertebroplasty.

Single and Multifraction Spine Stereotactic Body Radiation Therapy and the Risk of Radiation Induced Myelopathy.

Purpose: This study reports on the risk of radiation-induced myelitis (RM) of the spinal cord from a large single-institutional experience with 1 to 5 fraction stereotactic body radiation therapy (SBRT) to the spine. Methods and Materials: A retrospective review of patients who received spine SBRT to a radiation naïve level at or above the conus medullaris between 2007 and 2019 was performed. Local failure determination was based on SPIne response assessment in Neuro-Oncology criteria. RM was defined as neurologic symptoms consistent with the segment of cord irradiated in the absence of neoplastic disease recurrence and graded by Common Toxicity Criteria for Adverse Events, version 4.0. Rates of adverse events were estimated and dose-volume statistics from delivered treatment plans were extracted for the planning target volumes and spinal cord. Results: A total of 353 lesions in 277 patients were identified that met the specified criteria, for which 270, 70, and 13 lesions received 1-, 3-, and 5-fraction treatments, respectively, with a median follow-up of 46 months (95% confidence interval [CI], 41-52 months) for all surviving patients. The median overall survival was 33.0 months (95% CI, 29-43). The median D0.03cc to the spinal cord was 11.7 Gy (interquartile range [IQR], 10.5-12.4), 16.7 Gy (IQR, 12.8-20.6), and 26.0 Gy (IQR, 24.1-28.1), for 1-, 3-, 5-fractions. Using an a/b = 2Gy for the spinal cord, the median single-fraction equivalent-dose (SFED2) was 11.7 Gy (IQR, 10.2-12.5 Gy) and the normalized biological equivalent dose (nBED2/2) was 19.9 Gy (IQR, 15.4-22.8 Gy). One patient experienced grade 2 RM after a single-fraction treatment. The cumulative probability of RM was 0.3% (95% CI, 0%-2%). Conclusions: Spine SBRT is safe while limiting the spinal cord (as defined on treatment planning magnetic resonance imaging or computed tomography myelogram) D0.03cc to less than 14 Gy, 21.9 Gy, and 30 Gy, for 1, 3, and 5-fractions, consistent with standard guidelines.

The Game Continues: Seeking Clarity in the Radiation Oncology Match.

Though the previous Gaming the Match agreement offered guidance to programs on how best to approach the Match process, guidance for applicants remains inconsistent. Here we review and propose guidelines by which the spirit of the Match may better be achieved for both program directors and applicants alike.

Integrating Radiation Oncology Into Undergraduate Medical Education.

Cancer is one of the most important public health problems. However, medical education has not advanced at the same rate when it comes to cancer education. Currently, the United States Medical Licensing Examination subject examinations do not cover radiation oncology, prevention, and survivorship planning in its assessment model. Incorporating medical oncology and radiation oncology training into the undergraduate medical education curriculum can have a significant benefit in training future physicians. In this paper, we review current literature and propose some ideas that can help incorporate oncology, and specifically radiation oncology, into undergraduate medical education.

Ablative radiotherapy for ultracentral lung cancers: Dosimetric, geometric, and volumetric predictors of outcomes and toxicity.

BACKGROUND: Ultracentral lung cancers arise near the proximal bronchial tree (PBT), trachea, or esophagus, and have been associated with worse outcomes and increased toxicity after radiotherapy. We sought to associate dosimetric and anatomic factors with oncologic outcomes and toxicities. METHODS: One-hundred ten patients treated with ablative, curative-intent radiotherapy for ultracentral, node-negative, non-small cell lung cancer were included. Dosimetric and geometric data obtained using custom software that calculated volumes of target structures and organs-at-risk and measured the shortest vector length between these volumes were associated with outcomes and toxicity. RESULTS: Common dose/fractionation schemes included 50 Gy in 5 fractions (57%), 60 Gy in 8 fractions (15%), and 48 Gy in 4 fractions (13%). Overall survival at 1, 2, and 5 years was 78%, 57%, and 32%, respectively. Factors significantly associated with death included endobronchial tumor, gross tumor volume (GTV) or planning target volume (PTV) contacting PBT, shorter distance from GTV to PBT or esophagus, volume of PBT receiving prescription dose, higher pericardium max dose, lung V20Gy, and mean lung dose. Local progression at 1, 2, and 5 years was 4%, 16%, and 21%. Factors associated with local progression were lower GTV minimum dose and higher GTV/PTV volume ratio. Acute and late grade 2 + toxicity was seen in 18% and 27%, respectively. Four patients (4%) had fatal toxicity. CONCLUSIONS: Lower GTV minimum dose and smaller volumetric PTV expansions may increase risk of local progression, and should be balanced against normal tissue doses including pericardium maximum dose, lung V20Gy, and mean lung dose.