The Assistant Clinical Research Coordinator Program: A Pathway for Recruitment in Radiation Oncology.

Purpose: Recruiting prospective physicians to radiation oncology can be challenging, because of limited familiarity with the field. The Assistant Clinical Research Coordinator (ACRC) program can help provide trainees early exposure to radiation oncology. Methods and Materials: The ACRC program involves hiring a college graduate to provide administrative and research support for faculty members. The program was developed with our institution's clinical trials office, which provided guidance on regulatory compliance and training. A structured selection process identifies top candidates, and a rigorous onboarding process ensures smooth transitions between ACRCs. We report characteristics and outcomes of ACRC employees and surveyed them to assess their program experience using a Likert scale. Results: From 2005 to 2023, the ACRC program paired 73 ACRCs with faculty. Most faculty (68%) are currently supported by ACRCs. In 2023, 113 applications were received for 4 positions. ACRCs have contributed to research publications (293 as coauthors and 43 as first authors) and taken on leadership roles in the department. Most program alumni have attended medical school (34 of 64 program graduates; 53%). Eight have chosen to specialize in radiation oncology (13%; 2 applying into radiation oncology, 1 in residency, and 5 attendings). Of the 25% of alumni who responded to our survey, 77% responded that the mentorship provided by the ACRC program was very or extremely effective in guiding their academic development. All respondents rated the research opportunities as good or excellent, and 77% rated the clinical experience opportunities as good or excellent. Most (77%) reported that the ACRC program had substantial or significant influence on their choice of career path. Conclusions: The ACRC program provides an opportunity to address recruitment challenges in radiation oncology by offering early exposure to the field, clinical research skills, and mentorship. With the strong interest in our job posting this year, there is potential to expand this program to other institutions.

Shaping success: clinical implementation of a 3D-printed electron cutout program in external beam radiation therapy.

Purpose: The integration of 3D-printing technology into radiation therapy (RT) has allowed for a novel method to develop personalized electron field-shaping blocks with improved accuracy. By obviating the need for handling highly toxic Cerrobend molds, the clinical workflow is significantly streamlined. This study aims to expound upon the clinical workflow of 3D-printed electron cutouts in RT and furnish one year of in-vivo dosimetry data. Methods and materials: 3D-printed electron cutouts for 6x6 cm, 10x10 cm, and 15x15 cm electron applicators were designed and implemented into the clinical workflow after dosimetric commissioning to ensure congruence with the Cerrobend cutouts. The clinical workflow consisted of four parts: i) the cutout aperture was extracted from the treatment planning system (TPS). A 3D printable cutout was then generated automatically through custom scripts; ii) the cutout was 3D-printed with PLA filament, filled with tungsten ball bearings, and underwent quality assurance (QA) to verify density and dosimetry; iii) in-vivo dosimetry was performed with optically stimulated luminescence dosimeters (OSLDs) for a patient's first treatment and compared to the calculated dose in the TPS; iv) after treatment completion, the 3D-printed cutout was recycled. Results: QA and in-vivo OSLD measurements were conducted (n=40). The electron cutouts produced were 6x6 cm (n=3), 10x10 cm (n=30), and 15x15 cm (n=7). The expected weight of the cutouts differed from the measured weight by 0.4 + 1.1%. The skin dose measured with the OSLDs was compared to the skin dose in the TPS on the central axis. The difference between the measured and TPS doses was 4.0 + 5.2%. Conclusion: The successful clinical implementation of 3D-printed cutouts reduced labor, costs, and removed the use of toxic materials in the workplace while meeting clinical dosimetric standards.

An Affordable Platform for Virtual Reality-Based Patient Education in Radiation Therapy.

PURPOSE: The goal of this study was to develop and assess the effectiveness of an affordable smartphone-based virtual reality (VR) patient education platform with 360-degree videos produced depicting a first-person patient perspective during the radiation therapy (RT) care path to reduce patient anxiety. METHODS AND MATERIALS: Three disease site-specific (breast, pelvis, head and neck) VR videos were filmed using a 360-degree camera to portray the first-person perspective of a patient's standard RT appointments, including a computed tomography simulation and the first RT treatment session. Instruction is given for possible clinical implementation. Patient participation was divided into 2 groups: (1) Group A (n = 28) included patients participating before simulation and later after the first treatment, and (2) Group B (n = 33) included patients participating only while undergoing treatment. Patients viewed their disease site-specific video using an inexpensive cardboard VR viewer and their smartphone, emulating an expensive VR-headset. Surveys were administered assessing patient anxiety, comfort, satisfaction, and knowledge of RT on a 5-point Likert-type scale. RESULTS: Patients in Group A and Group B while undergoing treatment both indicated that their anxiety "decreased a little" in the survey, after watching the VR video (Group A, median on a 5-point Likert-type scale, 4 [IQR, 4-5]; Group B, 4 [IQR, 4-4]). The VR aspect of the videos was especially liked by patients while undergoing treatment, with 96.4% in Group A and 90.9% in Group B reporting that the VR aspect of the videos was helpful. All Group A participants believed that the VR videos would be beneficial to new patients. CONCLUSIONS: Our affordable VR patient education platform effectively immerses a patient in their care path from simulation through initial treatment delivery, reducing anxiety and increasing familiarity with the treatment process.

Long-term outcomes of patients with unfavorable stage I-II classic Hodgkin lymphoma treated with Stanford V chemotherapy and limited field irradiation.

Management of stage I-II unfavorable risk Hodgkin lymphoma (HL) strives to reduce toxicity while maintaining tumor control. Compared to ABVD or BEACOPP, Stanford V chemotherapy contains less doxorubicin and bleomycin. We report long-term outcomes of patients with stage I-II classic HL with European risk factors treated with Stanford V combined modality therapy (CMT). From our institutional cancer registry, we identified 168 patients with ≥1 European risk factor treated with 8-12 weeks of Stanford V CMT and consolidative radiotherapy between 1990 and 2016. Outcomes were analyzed after classification by EORTC and GHSG unfavorable criteria. With median follow-up of 8.4 years, 10-year overall survival and progression-free survival for the entire cohort were 95% and 88%, respectively. Thirteen of 18 relapses were salvaged successfully. There were no cases of MDS or AML after primary therapy. Long-term outcomes of stage I-II unfavorable risk HL treated with Stanford V CMT are comparable to ABVD or BEACOPP regimens.

Integrating Tumor and Nodal Imaging Characteristics at Baseline and Mid-Treatment Computed Tomography Scans to Predict Distant Metastasis in Oropharyngeal Cancer Treated With Concurrent Chemoradiotherapy.

PURPOSE: Prognostic biomarkers of disease relapse are needed for risk-adaptive therapy of oropharyngeal cancer (OPC). This work aims to identify an imaging signature to predict distant metastasis in OPC. METHODS AND MATERIALS: This single-institution retrospective study included 140 patients treated with definitive concurrent chemoradiotherapy, for whom both pre- and midtreatment contrast-enhanced computed tomography (CT) scans were available. Patients were divided into separate training and testing cohorts. Forty-five quantitative image features were extracted to characterize tumor and involved lymph nodes at both time points. By incorporating both imaging and clinicopathological features, a random survival forest (RSF) model was built to predict distant metastasis-free survival (DMFS). The model was optimized via repeated cross-validation in the training cohort and then independently validated in the testing cohort. RESULTS: The most important features for predicting DMFS were the maximum distance among nodes, maximum distance between tumor and nodes at mid-treatment, and pretreatment tumor sphericity. In the testing cohort, the RSF model achieved good discriminability for DMFS (C-index = 0.73, P = .008), and further divided patients into 2 risk groups with different 2-year DMFS rates: 96.7% versus 67.6%. Similar trends were observed for patients with p16+ tumors and smoking ≤10 pack-years. The RSF model based on pretreatment CT features alone achieved lower performance (concordance index = 0.68, P = .03). CONCLUSIONS: Integrating tumor and nodal imaging characteristics at baseline and mid-treatment CT allows prediction of distant metastasis in OPC. The proposed imaging signature requires prospective validation and, if successful, may help identify high-risk human papillomavirus-positive patients who should not be considered for deintensification therapy.

Cost-effectiveness of Screening for Nasopharyngeal Carcinoma among Asian American Men in the United States.

OBJECTIVE: Most patients with nasopharyngeal carcinoma (NPC) in the United States are diagnosed with stage III-IV disease. Screening for NPC in endemic areas results in earlier detection and improved outcomes. We examined the cost-effectiveness of screening for NPC with plasma Epstein-Barr virus DNA among Asian American men in the United States. STUDY DESIGN: We used a Markov cohort model to estimate discounted life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios for screening as compared with usual care without screening. SETTING: The base case analysis considered onetime screening for 50-year-old Asian American men. SUBJECTS AND METHODS: Confirmatory testing was magnetic resonance imaging and nasopharyngoscopy. Cancer-specific outcomes, health utility values, and costs were determined from cancer registries and the published literature. RESULTS: For Asian American men, usual care without screening resulted in the detection of NPC at stages I, II, III-IVB, and IVC among 6%, 29%, 54%, and 11% of those with cancer, respectively, whereas screening resulted in earlier detection with a stage distribution of 43%, 24%, 32%, and 1%. This corresponded to an additional 0.00055 QALYs gained at a cost of $63 per person: an incremental cost of $113,341 per QALY gained. In probabilistic sensitivity analysis, screening Asian American men was cost-effective at $100,000 per QALY gained in 35% of samples. CONCLUSION: Although screening for NPC with plasma Epstein-Barr virus DNA for 50-year-old Asian American men may result in earlier detection, in this study it was unlikely to be cost-effective. Screening may be reasonable for certain subpopulations at higher risk for NPC, but clinical studies are necessary before implementation.

Outcomes and Characteristics of Patients Treated with Emergent Palliative Radiation Therapy.

PURPOSE: Emergent palliative radiation therapy (PRT) of symptomatic metastases can significantly increase the quality of life of patients with cancer. In some contexts, this treatment may be underused, but in others PRT may represent an excessively aggressive intervention. The characterization of the current use of emergent PRT is warranted for optimized value and patient-centered care. METHODS AND MATERIALS: This study is a cross-sectional retrospective analysis of all emergent PRT courses at a single academic tertiary institution across 1 year. RESULTS: A total of 214 patients received a total of 238 treatment courses. The most common indications were bone (39%) and brain (14%) metastases. Compared with outpatients, inpatients had lower mean survival rates (2 months vs 6 months; P < .001), higher rates of stopping treatment early (19.1% vs 9.0%; P = .034), and greater involvement of palliative care (44.8% vs 24.1%; P < .001), but the same mean planned fractions (9.10 vs 9.40 fractions; P = .669). In a multiple predictor survival analysis, palliative care involvement (P = .025), male sex (P = .001), ending treatment early (P = .011), and having 1 of 3 serious indications (airway compromise, leptomeningeal disease, and superior/inferior vena cava involvement; P = .007) were significantly associated with worse overall survival. CONCLUSIONS: Survival is particularly poor in patients who receive emergent PRT, and patient characteristics such as functional status and indication should be considered when determining fractionation schedule and dosing. A multi-institutional study of practice patterns and outcomes is warranted.

Invasive nodal evaluation prior to stereotactic ablative radiation for non-small cell lung cancer.

INTRODUCTION: Invasive nodal evaluation (INE) is used to improve staging for early stage non-small cell lung cancer (NSCLC), including when stereotactic ablative radiation (SABR) is used. Consensus guidelines from the NCCN recommend performing INE for patients with T2N0 tumors and considering INE for those with T1N0 tumors. We reasoned that if INE results in significant stage migration in the form of substantially fewer patients with occult nodal involvement, then patients treated with SABR who do not undergo INE should have worse overall survival (OS). METHODS: Patients diagnosed 2004-2014 with stage T1-2N0M0 NSCLC and treated with SABR were identified from the National Cancer Database. Factors associated with INE were determined using mixed effects logistic regression. We tested for an association between INE and OS for patients diagnosed 2004-2013 using mixed effects proportional hazards regression methods. RESULTS: 24,603 SABR patients were identified. 6% of the 19,322 patients with T1 tumors and 9% of the 5281 patients with T2 tumors had INE. Median OS was 2.8 years for the no-INE group and 2.7 years for the INE group (log-rank P = 0.69). No significant association was observed between the use of INE and OS in the univariate analysis (HR 1.02, 95% CI 0.94-1.11) or the multivariate analysis (HR 0.94, 95% CI 0.86-1.02). These findings were confirmed using propensity score matched and instrumental variable analysis. On subgroup analysis, INE was associated with a non-significant trend for improved OS in patients with T2 tumors (HR 0.87, 95% CI 0.76-1.00) but not T1 tumors (HR 0.98, 95% CI 0.88-1.09). CONCLUSIONS: Despite current NCCN recommendations, the rate of INE was low for patients with stage T1 or T2 tumors. While omitting INE represents a compromise in the completeness of nodal evaluation, we found that it was not associated with a detriment in overall survival.

Rising rates of bilateral mastectomy with reconstruction following neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) is used to allow more limited breast surgery without compromising local control. We sought to evaluate nationwide surgical trends in patients with operable breast cancer treated with NAC and factors associated with surgical type. We used the National Cancer Database to identify 235,339 women with unilateral T1-3 N0-3 M0 breast cancer diagnosed between 2010 and 2014 and treated with surgery and chemotherapy. Of these, 59,568 patients (25.3%) were treated with NAC. Rates of pathological complete response (pCR) to NAC increased from 33.3% at the start of the study period in 2010 to 46.3% at the end of the period in 2014 (p = 0.02). Rates of breast-conserving surgery (BSC) changed little, from 37.0 to 40.8% (p = 0.22). Although rates of unilateral mastectomy decreased from 43.3 to 34.7% (p = 0.02) and rates of bilateral mastectomy without immediate reconstruction remained similar (11.7-11.5%; p = 0.82), rates of bilateral mastectomy with immediate reconstruction rose from 8.0 to 13.1% (p = 0.02). Patients who were younger, with private/managed care insurance, and diagnosed in more recent years were more likely to achieve pCR; however, these same characteristics were associated with receipt of bilateral mastectomy (vs. BCS). In addition, non-Hispanic white ethnic and higher area education attainment were both associated with bilateral mastectomy. These findings did not differ by age or molecular subtype. Further study of nonclinical factors that influence selection of more extensive surgery despite excellent response to NAC is warranted.

18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy.

PURPOSE: Tumor hypoxia contributes to radiation resistance. A noninvasive assessment of tumor hypoxia would be valuable for prognostication and possibly selection for hypoxia-targeted therapies. 18F-pentafluorinated etanidazole (18F-EF5) is a nitroimidazole derivative that has demonstrated promise as a positron emission tomography (PET) hypoxia imaging agent in preclinical and clinical studies. However, correlation of imageable hypoxia by 18F-EF5 PET with clinical outcomes after radiation therapy remains limited. METHODS AND MATERIALS: Our study prospectively enrolled 28 patients undergoing radiation therapy for localized lung or other tumors to receive pretreatment 18F-EF5 PET imaging. Depending on the level of 18F-EF5 tumor uptake, patients underwent functional manipulation of tumor oxygenation with either carbogen breathing or oral dichloroacetate followed by repeated 18F-EF5 PET. The hypoxic subvolume of tumor was defined as the proportion of tumor voxels exhibiting higher 18F-EF5 uptake than the 95th percentile of 18F-EF5 uptake in the blood pool. Tumors with a hypoxic subvolume ≥ 10% on baseline 18F-EF5 PET imaging were classified as hypoxic by imaging. A Cox model was used to assess the correlation between imageable hypoxia and clinical outcomes after treatment. RESULTS: At baseline, imageable hypoxia was demonstrated in 43% of all patients (12 of 28), including 6 of 16 patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy and 6 of 12 patients with other cancers. Carbogen breathing was significantly associated with decreased imageable hypoxia, while dichloroacetate did not result in a significant change under our protocol conditions. Tumors with imageable hypoxia had a higher incidence of local recurrence at 12 months (30%) than those without (0%) (P < .01). CONCLUSIONS: Noninvasive hypoxia imaging by 18F-EF5 PET identified imageable hypoxia in about 40% of tumors in our study population. Local tumor recurrence after highly conformal radiation therapy was higher in tumors with imageable hypoxia.

Impact of Intensity-Modulated Radiotherapy on Health Care Costs of Patients With Anal Squamous Cell Carcinoma.

PURPOSE: Drivers of variation in the cost of care after chemoradiotherapy for the management of anal squamous cell carcinoma (SCC) have not been fully elucidated. We sought to characterize the direct and indirect impact of radiotherapy modality on health care costs among patients with anal SCC. PATIENTS AND METHODS: A retrospective cohort study was performed using the 2014 linkage of the SEER-Medicare database. We identified 1,025 patients with anal SCC diagnosed between 2001 and 2011 and treated with chemoradiotherapy. Propensity score matching was used to balance baseline differences between patients treated with intensity-modulated radiotherapy (IMRT) and those treated with three-dimensional conformal radiotherapy (3D-CRT). Differences in total, cancer-attributable, and procedure-specific costs between groups were measured. RESULTS: Radiation-related, patient out-of-pocket, and total costs in the 1-year period after radiotherapy start were all higher for the IMRT group than the 3D-CRT group (median total cost, $35,890 v $27,262, respectively; P < .001). Patients who received IMRT had lower cumulative costs associated with urgent hospitalizations and emergency department visits at both 9 months and 1 year after treatment start compared with a matched cohort of patients who received 3D-CRT (median, $711 v $4,957 at 1 year, respectively; P = .021). CONCLUSION: Although total costs of care were higher for IMRT compared with 3D-CRT, primarily as a result of higher radiotherapy-specific costs, IMRT was associated with decreased unplanned health care utilization costs starting at 9 months after treatment start. Radiotherapy-centered episodes of care may need to encompass a longer time horizon to capture the full cost savings associated with more advanced radiation modalities.

Nonoperative Management of Rectal Cancer: A Modern Perspective.

Nonoperative management of rectal cancer is an emerging treatment approach that aims to enable carefully selected patients to avoid the morbidity of radical surgical resection, while benefiting from the same excellent rates of tumor control achieved with radical surgery-based combined-modality therapy. The success of nonoperative management in this setting is based on the accurate assessment of tumor eradication after chemoradiotherapy, without pathologic verification. Therefore, clinical evidence of complete response-based on physical examination, endoscopic procedures, and imaging-must be utilized as a marker to predict for pathologic complete response and thus help select the patients who are most appropriate for nonoperative management. Initial evidence from retrospective and prospective single-arm and cohort studies has demonstrated high rates of local control and disease-free survival with nonoperative management of rectal cancer, compared with historical results of combined-modality therapy. Several trials and registries are prospectively investigating nonoperative management vs standard treatment of rectal cancer. At this time, combined-modality therapy with total mesorectal excision remains the standard of care for patients with locally advanced rectal cancer; nonoperative management should not be routinely offered outside of clinical trials.

Extent of lymphovascular space invasion may predict lymph node metastasis in uterine serous carcinoma.

OBJECTIVES: Emerging evidence suggests that extent of lymphovascular space invasion (LVSI) predicts for risk of lymph node metastasis in endometrioid uterine cancers. However, this correlation remains unknown in the setting of uterine serous carcinoma (USC). We sought to examine the association between extent of LVSI and other histopathologic characteristics with risk of nodal metastasis for women with USC. MATERIALS/METHODS: Pathological data from all cases of uterine serous carcinoma between July 1998 to July 2015 at our institution were reviewed. Descriptive, univariate, and multivariate logistic regression analysis of selected pathologic features were performed. RESULTS: 88 patients with USC underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy. Surgical staging revealed the following FIGO stage distributions: I (41%), II (8%), III (32%), IV (19%). LVSI was present in 44 (50%) patients. 36 patients (41%) had LN metastases with median number of total nodes removed of 17 (range, 1-49). On univariate analysis, depth of myometrial invasion, LVSI, tumor size, and cervical stromal involvement were significantly associated with nodal involvement. In a multivariate model, LVSI (OR 6.25, 95% CI 2.2-18.0, p<0.01) and cervical stromal involvement (OR 3.33, 95% CI 1.10-10.0, p=0.03) were the only factors that remained significant. Among patients with LVSI-positive disease, extensive LVSI was associated with increased risk of nodal involvement compared to focal LVSI (90% vs 29%, p=0.04). CONCLUSIONS: Presence and extent of LVSI, and cervical stromal invasion are important predictors for lymph node metastasis in uterine serous carcinoma.

Sinoatrial node toxicity after stereotactic ablative radiation therapy to lung tumors.

PURPOSE: Stereotactic ablative radiation therapy (SABR) is an established treatment for selected lung tumors. Sinoatrial node (SAN) toxicity after thoracic SABR has not been reported in the literature. We sought to understand the risk of SAN toxicity owing to incidental dose to the SAN from SABR. METHODS AND MATERIALS: We conducted a retrospective review of patients with early-stage lung cancer or limited pulmonary metastases who underwent thoracic SABR to a right-sided central lung tumor (within 2 cm of the mainstem bronchus or other mediastinal structures) between January 2008 and December 2014, analyzed a subset whose treatment imparted dose to the SAN exceeding 10% of the prescription dose, and examined patient and treatment dosimetric characteristics. Mean follow-up interval was 28 months. Time to toxicity was defined from start of SABR. RESULTS: Of 47 patients with central tumors in the right lung treated with SABR reviewed, 13 met our study criteria. A contouring atlas of regional cardiac anatomy was created. One patient treated with SABR for non-small cell lung cancer at the right hilum developed symptomatic sick sinus syndrome, requiring pacemaker placement 6 months after treatment. Her acute presentation and short interval between SABR and onset of symptoms suggest that SAN toxicity was likely due to radiation-induced injury. Both her age and mean dose to her SAN were the third highest in our cohort. She remained free from cancer progression at 24 months' follow-up. Twelve additional patients who received significant dose to the SAN from SABR did not develop toxicity. CONCLUSION: While uncommon, SAN toxicity from SABR to right-sided central thoracic tumors should be recognized and followed in future studies.

Cost-effectiveness of radiation and chemotherapy for high-risk low-grade glioma.

BACKGROUND: The addition of procarbazine, lomustine, vincristine (PCV) chemotherapy to radiotherapy (RT) for patients with high-risk (≥40 y old or subtotally resected) low-grade glioma (LGG) results in an absolute median survival benefit of over 5 years. We evaluated the cost-effectiveness of this treatment strategy. METHODS: A decision tree with an integrated 3-state Markov model was created to follow patients with high-risk LGG after surgery treated with RT versus RT+PCV. Patients existed in one of 3 health states: stable, progressive, or dead. Survival and freedom from progression were modeled to reflect the results of RTOG 9802 using time-dependent transition probabilities. Health utility values and costs of care were derived from the literature and national registry databases. Analysis was conducted from the health care perspective. Deterministic and probabilistic sensitivity analysis explored uncertainty in model parameters. RESULTS: Modeled outcomes demonstrated agreement with clinical data in expected benefit of addition of PCV to RT. The addition of PCV to RT yielded an incremental benefit of 4.77 quality-adjusted life-years (QALYs) (9.94 for RT+PCV vs 5.17 for RT alone) at an incremental cost of $48635 ($188234 for RT+PCV vs $139598 for RT alone), resulting in an incremental cost-effectiveness ratio of $10186 per QALY gained. Probabilistic sensitivity analysis demonstrates that within modeled distributions of parameters, RT+PCV has 99.96% probability of being cost-effectiveness at a willingness-to-pay threshold of $100000 per QALY. CONCLUSION: The addition of PCV to RT is a cost-effective treatment strategy for patients with high-risk LGG.

Hypofractionated Intensity-Modulated Radiotherapy for Patients With Non-Small-Cell Lung Cancer.

BACKGROUND: Alternative treatment regimens are needed for patients with non-small cell lung cancer (NSCLC) who cannot receive definitive treatment with concurrent chemoradiotherapy, surgery, or stereotactic ablative radiotherapy (SABR). PATIENTS AND METHODS: We report survival, patterns of failure and toxicity outcomes for patients with NSCLC who were not eligible for surgical resection, concurrent chemoradiotherapy, or SABR and underwent hypofractionated intensity-modulated radiotherapy (IMRT). Kaplan-Meier survival analysis was used to evaluate the progression-free and overall survival. Competing risk analysis was used to evaluate in-field, locoregional, and distant failure. RESULTS: A total of 42 patients treated to 52.5 to 60 Gy in 15 fractions were included. Most of the patients had metastatic or recurrent disease (64%) and a relatively large, centrally located tumor burden (74%). The median follow-up period was 13 months (interquartile range, 6-18 months). All patients received the total prescribed dose. The median survival was 15.1 months. The overall and progression-free survival rates at 1 year were 63% and 22.5%, respectively. The pattern of failure was predominantly distant, with only 2% of patients experiencing isolated in-field recurrence. The cumulative incidence of in-field failure at 6 and 12 months was 2.5% (95% confidence interval, 0.4%-15.6%) and 16.1% (95% confidence interval, 7.5%-34.7%), respectively. The risk of esophageal toxicity was associated with the esophageal mean dose, maximal point dose, and dose to the 5 cm3 volume. The risk of pneumonitis was associated with the lung mean dose and volume receiving 18 Gy. CONCLUSION: Hypofractionated IMRT without concurrent chemotherapy provides favorable rates of local control and survival for well-selected patients with NSCLC who cannot tolerate standard definitive therapy.

Pre-treatment non-target lung FDG-PET uptake predicts symptomatic radiation pneumonitis following Stereotactic Ablative Radiotherapy (SABR).

PURPOSE: To determine if pre-treatment non-target lung FDG-PET uptake predicts for symptomatic radiation pneumonitis (RP) following lung stereotactic ablative radiotherapy (SABR). METHODS: We reviewed a 258 patient database from our institution to identify 28 patients who experienced symptomatic (grade â©¾ 2) RP after SABR, and compared them to 57 controls who did not develop symptomatic RP. We compared clinical, dosimetric and functional imaging characteristics between the 2 cohorts including pre-treatment non-target lung FDG-PET uptake. RESULTS: Median follow-up time was 26.9 months. Patients who experienced symptomatic RP had significantly higher non-target lung FDG-PET uptake as measured by mean SUV (p < 0.0001) than controls. ROC analysis for symptomatic RP revealed area under the curve (AUC) of 0.74, with sensitivity 82.1% and specificity 57.9% with cutoff mean non-target lung SUV > 0.56. Predictive value increased (AUC of 0.82) when mean non-target lung SUV was combined with mean lung dose (MLD). We developed a 0-2 point model using these 2 variables, 1 point each for SUV > 0.56 or MLD > 5.88 Gy equivalent dose in 2 Gy per fraction (EQD2), predictive for symptomatic RP in our cohort with hazard ratio 10.01 for score 2 versus 0 (p < 0.001). CONCLUSIONS: Patients with elevated pre-SABR non-target lung FDG-PET uptake are at increased risk of symptomatic RP after lung SABR. Our predictive model suggests patients with mean non-target lung SUV > 0.56 and MLD > 5.88 Gy EQD2 are at highest risk. Our predictive model should be validated in an external cohort before clinical implementation.

Severe Chest Wall Toxicity From Cryoablation in the Setting of Prior Stereotactic Ablative Radiotherapy.

We present the case of a 42-year-old woman with metastatic synovial sarcoma of parotid origin, treated definitively with chemoradiation, who subsequently developed oligometastatic disease limited to the lungs. She underwent multiple left and right lung wedge resections and left lower lobectomy, followed by right lower lobe stereotactic ablative radiotherapy (SABR), 54 Gy in three fractions to a right lower lobe lesion abutting the chest wall. Two years later, she was treated with cryoablation for a separate right upper lobe nodule abutting the chest wall. Two months later, she presented with acute shortness of breath, pleuritic chest pain, decreased peripheral blood O2 saturation, and productive cough. A computed tomography (CT) scan demonstrated severe chest wall necrosis in the area of recent cryoablation that, in retrospect, also received a significant radiation dose from her prior SABR. This case demonstrates that clinicians should exercise caution in using cryoablation when treating lung tumors abutting a previously irradiated chest wall. Note: Drs. Loo and Shah contributed equally as co-senior authors.

Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.

PURPOSE: The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab. PATIENT AND METHODS: We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions. RESULTS: Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained. CONCLUSION: THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States.