High dose total marrow irradiation (TMI) does not increase long-term toxicity of myeloablative fludarabine/busulfan (FluBu4) conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT).

OBJECTIVES: Based on a previous phase 1 study, total marrow irradiation (TMI) at 9Gy was added to a myeloablative FluBu4 conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for myeloid malignancies. Here, we report on the long-term toxicity of TMI combined with FluBu4 and compare it to patients who received only FluBu4. METHODS: We retrospectively analyzed 38 consecutive patients conditioned with FluBu4/TMI (n = 15) or FluBu4 (n = 23, control group) who had at least 1 year follow-up post-transplant. The rate of long-term adverse events that have been previously associated with total body irradiation (TBI) was analyzed in the two groups. RESULTS: The baseline characteristics did not differ between the two groups. The control group had a longer median follow-up (71.2 mo) than the TMI group (38.5 mo) (p = .004). The most common adverse events were xerostomia, dental complications, cataracts, or osteopenia and did not differ between the two groups. Cognitive dysfunction or noninfectious pneumonitis, often detected after high dose TBI, were also not different in the two groups (p = .12 and p = .7, respectively). There was no grade 4 adverse event. CONCLUSION: Our results suggest that a conditioning regimen with TMI 9Gy and FluBu4 does not increase long-term adverse events after allogeneic HSCT.

SBRT for Liver Tumors: What the Interventional Radiologist Needs to Know.

This review summarizes the clinical evidence supporting the utilization of stereotactic body radiotherapy (SBRT) for liver tumors, including hepatocellular carcinoma, liver metastases, and cholangiocarcinoma. Emerging prospective evidence has demonstrated the benefit and low rates of toxicity across a broad range of clinical contexts. We provide an introduction for the interventional radiologist, with a discussion of underlying themes such as tumor dose-response, mitigation of liver toxicity, and the technical considerations relevant to performing liver SBRT. Ultimately, we recommend that SBRT should be routinely included in the armamentarium of locoregional therapies for liver malignancies, alongside those liver-directed therapies offered by interventional radiology.

The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Increased Utilization of Stereotactic Body Radiotherapy is Associated with Decreased Disparities and Improved Survival for Early-Stage NSCLC.

INTRODUCTION: We sought to determine if increased use of stereotactic body radiation therapy (SBRT) was associated with decreased disparities in the receipt of definitive treatment for early-stage non-small cell lung cancer (NSCLC). METHODS: The National Cancer Database (NCDB) was utilized to determine the proportion of patients with NSCLC receiving surgery, SBRT, or no definitive treatment for clinical cT1-2aN0M0 NSCLC from 2004-2017. Univariable and multivariable logistic regressions were used. Age-adjusted mortality rates were calculated using the Surveillance, Epidemiology, and End Result (SEER) database. RESULTS: From 2004 to 2017, the proportion of early-stage NSCLC undergoing no definitive treatment declined from 22% to 10.5% (P<.001), while the proportion receiving SBRT increased from 1% (0.9%-1.3%) to 22% (21.4%-22.3%; P<.001). Among Whites, the proportion undergoing no definitive treatment decreased from 21% to 10% (P<.001), as compared to Blacks, which had a higher decrease, of 32% to 15% (P<.001). The proportion of Blacks receiving SBRT increased from 1% (0.3%-1.7%) to 22% (20.8%-23.5%) (P<.001). Between 2011 and 2017 likelihood of Blacksreceiving curative therapy increased compared to Whites [OR: 0.55 (0.48-0.64) to 0.70 (0.62-0.79; P<.001]. Furthermore, the age-adjusted mortality rate of early-stage NSCLC decreased from 4.3 (4.0-4.5) in 2004 to 0.8 (0.7-0.9) in 2017 (P<.001). CONCLUSIONS: Increased utilization of SBRT significantly increased the proportion of patients receiving curative therapy for early-stage NSCLC and was associated with an improvement in mortality.  Furthermore, the use of SBRT reduced previously seen disparities in receipt of treatment between Whites and Blacks. SBRT was also associated with decreased mortality from early-stage NSCLC.

Knowledge-based planning for multi-isocenter VMAT total marrow irradiation.

Purpose: Total marrow irradiation (TMI) involves optimization of extremely large target volumes and requires extensive clinical experience and time for both treatment planning and delivery. Although volumetric modulated arc therapy (VMAT) achieves substantial reduction in treatment delivery time, planning process still presents a challenge due to use of multiple isocenters and multiple overlapping arcs. We developed and evaluated a knowledge-based planning (KBP) model for VMAT-TMI to address these clinical challenges. Methods: Fifty-one patients previously treated in our clinic were selected for the model training, while 22 patients from another clinic were used as a test set. All plans used a 3-isocenter to cover sub-target volumes of head and neck (HN), chest, and pelvis. Chest plan was performed first and then used as the base dose for both the HN and pelvis plans to reduce hot spots around the field junctions. This resulted in a wide range of dose-volume histograms (DVH). To address this, plans without the base-dose plan were optimized and added to the library to train the model. Results: KBP achieved our clinical goals (95% of PTV receives 100% of Rx) in a single day, which used to take 4-6 days of effort without KBP. Statistically significant reductions with KBP were observed in the mean dose values to brain, lungs, oral cavity and lenses. KBP substantially improved 105% dose spillage (14.1% ± 2.4% vs 31.8% ± 3.8%), conformity index (1.51 ± 0.06 vs 1.81 ± 0.12) and homogeneity index (1.25 ± 0.02 vs 1.33 ± 0.03). Conclusions: KBP improved dosimetric performance with uniform quality. It reduced dependence on planner experience and achieved a factor of 5 reduction in planning time to produce quality plans to allow its wide-spread clinical implementation.

Brain arteriovenous malformation flow after stereotactic radiosurgery: Role of quantitative MRA.

BACKGROUND: Stereotactic radiosurgery (SRS) is a current therapeutic option for treatment of arteriovenous malformations (AVMs) located in deep or eloquent brain regions. Obliteration usually occurs in a delayed fashion, with an expected latency of 3-5 years. Here, we assess how AVM flow correlates with volume before and after SRS treatment. METHODS: Patients with supratentorial AVM treated with SRS at our institution between 2012-2022 were retrospectively reviewed. Patients were included if Quantitative Magnetic Resonance Angiography (QMRA) study was performed at baseline and at least at the first follow-up. Correlation between AVM flow and volume before and after treatment was evaluated. AVM flow and volume were additionally assessed for obliteration using the non-parametric receiver operating characteristic (ROC) curve. RESULTS: Twelve patients with radiologic follow-up imaging were included. Eight patients presented AVM rupture, one of which occurred after radiosurgical treatment. Three patients underwent embolization prior SRS. Mean AVM initial volume was 3.8 cc (0.1-12.4 cc), mean initial flow 174 ml/min (11-604 ml/min), both variables showed progressive reduction at follow-up (range 3-57 months); and flow decreased with volume reduction (p < 0.001). Area under the ROC was 0.914 for both AVM flow and volume with obliteration (p = 0.019). CONCLUSIONS: AVM flow significantly decreased after SRS treatment, reflecting volume reduction. Baseline AVM flow and volume both predicted obliteration. QMRA provides additional non-invasive information to monitor patients after radiosurgical treatment.

Development and Validation of a Decision Analytical Model for Posttreatment Surveillance for Patients With Oropharyngeal Carcinoma.

Importance: Clinical practice regarding posttreatment radiologic surveillance for patients with oropharyngeal carcinoma (OPC) is neither adapted to individual patient risk nor fully evidence based. Objectives: To construct a microsimulation model for posttreatment OPC progression and use it to optimize surveillance strategies while accounting for both tumor stage and human papillomavirus (HPV) status. Design, Setting, and Participants: In this decision analytical modeling study, a Markov model of 3-year posttreatment patient trajectories was created. The training data source was the American College of Surgeon's National Cancer Database from 2010 to 2015. The external validation data set was the 2016 International Collaboration on Oropharyngeal Cancer Network for Staging (ICON-S) study. Training data comprised 2159 patients with OPC treated with primary radiotherapy who had known HPV status and disease staging information. Patients with American Joint Committee on Cancer, 7th edition stage III to IVB disease and those with clinical metastases during the time of primary treatment were included. Data were analyzed from August 1 to October 31, 2020. Main Outcomes and Measures: Main outcomes included disease stage and HPV status, specific disease transition probabilities, and latency of surveillance regimens, defined as time between recurrence incidence and disease discovery. Results: Training data consisted of 2159 total patients (1708 men [79.1%]; median age, 59.6 years [range, 40-90 years]; 401 with stage III disease, 1415 with stage IVA disease, and 343 with stage IVB disease). Cohorts predominantly had HPV-negative disease (1606 [74.4%]). With model-optimized regimens, recurrent disease was discovered a mean of 0.6 months (95% CI, 0.5-0.8 months) earlier than with a standard surveillance regimen based on current clinical guidelines. Recurrent disease was discovered using the optimized regimens without significant reduction in sensitivity. Compared with strategies based on reimbursement guidelines, the model-optimized regimens found disease a mean of 1.8 months (95% CI, 1.3-2.3 months) earlier. Conclusions and Relevance: Optimized, risk-stratified surveillance regimens consistently outperformed nonoptimized strategies. These gains were obtained without requiring any additional imaging studies. This approach to risk-stratified surveillance optimization is generalizable to a broad range of tumor types and risk factors.

Decreased overall survival in patients with locally advanced head and neck cancer receiving definitive radiotherapy and concurrent cetuximab: National Cancer Database analysis.

BACKGROUND: Recently, randomized trials have questioned the efficacy of cetuximab-based bioradiotherapy compared to chemoradiation for patients with squamous cell carcinoma of the oropharynx, larynx, and hypopharynx (HNSCC). We compared the OS of patients treated with radiotherapy alone (RTonly), chemoradiotherapy (chemoRT), and bioradiotherapy (cetuxRT). METHODS: Patients with stage III-IVB HNSCC treated with RTonly, chemoRT, or cetuxRT were identified in the National Cancer Database. OS was estimated using Cox proportional hazards. Analyses were conducted on the overall cohort and propensity matched cohorts. RESULTS: 31 014 patients were treated with RTonly (22%), chemoRT (72%), or cetuxRT (6%) from 2013 to 2016. The 2-year OS was 69% for RTonly, 79% for chemoRT, and 66% for cetuxRT (p < 0.001). In the overall and propensity-matched cohorts, chemoRT and RTonly were associated with improved OS as compared to cetuxRT (p ≤ 0.001). CONCLUSION: Compared to chemoRT or RTonly, cetuxRT is associated with decreased OS for patients with HNSCC, suggesting minimal benefit of bioradiotherapy in this population.

Increased Disparities in Patients Diagnosed with Metastatic Lung Cancer Following Lung CT Screening in the United States.

OBJECTIVES: We sought to determine if implementation of low dose computed tomography (LDCT) screening for lung cancer in the United States had led to changes in patients being diagnosed with metastatic lung cancer over time. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Result (SEER) database was utilized to determine the proportion of lung cancers diagnosed as stage I to III and stage IV from 2009-2018. Changes in lung cancer stage distribution were compared in the overall population and by race. RESULTS: From 2009 to 2018, the proportion of stage I to III lung cancers increased from 52% (51.3%-53.2%) in 2009 to 56% (54.0%-55.8%) in 2018 (P < .001). Correspondingly, the proportion of lung cancers diagnosed in stage IV decreased from 48% (46.8%-48.7%) in 2009 to 45% (44.2%-46.0%) (P < .001) in 2018. For white patients, the proportion increased from 53% (51.6%-53.7%) to 56% (55.1%-57.1%) (P < .001). However, for black patients, no trend was present, with the proportion being 51% (47.9%-53.4%) in 2009 and 52% (49.0%-54.2%) in 2018 (P = .303). CONCLUSION: Since the implementation of LDCT screening, the proportion of early-stage lung cancers increased in the general population. These changes in stage distribution were not present in black patients.

Addressing Sex Disparities in Lung Cancer Screening Eligibility: USPSTF vs PLCOm2012 Criteria.

BACKGROUND: Lung cancer is the leading cause of cancer death in women in the United States. Prospective randomized lung screening trials suggest a greater lung cancer mortality benefit from screening women compared with men. RESEARCH QUESTION: Do the United States Preventative Services Task Force (USPSTF) lung screening guidelines that are based solely on age and smoking history contribute to sex disparities in eligibility, and if so, does the use of the PLCOm2012 risk prediction model that is based on 11 predictors of lung cancer reduce sex disparities? STUDY DESIGN AND METHODS: This retrospective analysis of 883 lung cancer cases in the Chicago Race Eligibility for Screening Cohort (CREST) determined the sensitivity of USPSTF vs PLCOm2012 eligibility criteria, stratified according to sex. For comparisons vs the USPSTF 2013 and the recently published USPSTF 2021 (released March 9, 2021) eligibility criteria, the PLCOm2012 model was used with risk thresholds of ≥ 1.7%/6 years (6y) and ≥ 1.0%/6y, respectively. RESULTS: The sensitivities for screening by the USPSTF 2013 were 46.7% for women and 64.6% for men (P = .003) and by the USPSTF 2021 were 56.8% and 71.8%, respectively (P = .02). In contrast, the PLCOm2012 ≥ 1.7%/6y sensitivities were 64.6% and 70.4%, and the PLCOm2012 ≥ 1.0%/6y sensitivities were 77.4% and 82.4%. The PLCOm2012 differences in sensitivity using ≥ 1.7%/6y and ≥ 1.0%/6y thresholds between women and men were nonsignificant (both, P = .07). Compared with men, women were more likely to be ineligible according to the USPSTF 2021 criteria because their smoking exposures were < 20 pack-years (22.8% vs 14.8%; ORWomen vs Men, 1.70; 95% CI, 1.19-2.44; P = .002), and 27% of these ineligible women were eligible according to the PLCOm2012 ≥ 1.0%/6y criteria. INTERPRETATION: Although the USPSTF 2021 eligibility criteria are more sensitive than the USPSTF 2013 guidelines, sex disparities in eligibility remain. Adding the PLCOm2012 risk prediction model to the USPSTF guidelines would improve sensitivity and attenuate sex disparities.

Brief Report: Risk Prediction Model Versus United States Preventive Services Task Force 2020 Draft Lung Cancer Screening Eligibility Criteria-Reducing Race Disparities.

INTRODUCTION: Eligibility criteria for lung cancer screening based solely on age and smoking history are less sensitive than validated risk prediction models. The U.S. Preventive Services Task Force (USPSTF) has proposed new guidelines to improve the sensitivity for selecting high-risk individuals and to decrease race disparity. In this retrospective study, termed the Chicago Race Eligibility for Screening Cohort, we compare the sensitivity of the proposed USPSTF2020 criteria versus the PLCOm2012 risk prediction model for selecting a racially diverse lung cancer population with a smoking history for lung cancer screening. METHODS: This Chicago Race Eligibility for Screening Cohort study applies the PLCOm2012 model with a risk threshold of 1.0%/6 years and the USPSTF2020 criteria (age 50-80 y, pack-years ≥ 20 y, quit-years ≤ 15 y) to 883 individuals with a smoking history diagnosed with having lung cancer. RESULTS: The PLCOm2012 was more sensitive than the USPSTF2020 overall (79.1% versus 68.6%, p < 0.0001) in White (81.5% versus 75.4%, p = 0.029) and in African American (82.8% versus 70.6% p < 0.0001) individuals. Of the total cohort, 254 (28.8%) would not have qualified owing to less than 20 pack-years, quit-time of more than 15 years, and age less than 50 years. Of these 254 cases, 40% would have qualified by the PLCOm2012 model. For the 20 pack-year criterion, of the 497 African American individuals, 19.3% did not meet this criterion, and of these, an additional 31.3% would have qualified by the PLCOm2012 model (p = 0.002). CONCLUSIONS: Although more sensitive than USPSTF2013, the proposed USPSTF2020 draft guidelines still have a race disparity in eligibility for screening. This study provides "real world" evidence that use of the PLCOm2012 risk prediction model eliminates this race disparity.

Impact of anatomic site of distant metastasis on survival in salivary gland cancers.

BACKGROUND: As exemplified in patients with adenoid cystic carcinoma (ACC), metastatic salivary gland cancers display heterogenous behavior. Although anatomic site of metastasis has been suggested to be prognostic for survival in this population, this is not adequately characterized in the current literature. METHODS: Using the National Cancer Database (NCDB), patients with newly diagnosed metastatic salivary gland cancers with distant metastasis to a single organ were identified. RESULTS: Eight hundred and fifty-eight patients (n = 284 bone-only, n = 322 lung-only, n = 252 other-site-only) were identified. Anatomic site of distant metastasis was not associated with survival in the cohort as a whole; however, on pre-planned subgroup analysis, lung-only metastasis, relative to bone-only metastasis, was the only factor associated with improved survival in patients with ACC (HR: 0.52, 95%CI: 0.30-0.93, p = 0.029). CONCLUSIONS: Anatomic site of metastasis is strongly associated with survival in patients with metastatic ACC and should be considered in future studies aiming to optimize therapy in this population.

Patterns of Care and Survival Outcomes for Odontogenic Cancers.

OBJECTIVES: Our understanding of odontogenic cancers is limited primarily to case studies given the rarity of these head and neck neoplasms. Using the National Cancer Database, we report the treatment patterns and survival outcomes for one of the largest cohorts of patients with odontogenic cancers. METHODS: Patients with odontogenic tumors who did not have metastatic disease and received at least part of their care at the reporting facility were included. Patient and treatment variables were assessed using logistic regression. Survival was assessed using Cox proportional hazard models. RESULTS: We identified 437 patients with odontogenic cancers, the majority of which had malignant ameloblastoma (n = 203) or odontogenic carcinoma (n = 217). Median follow-up was 44.8 months. On multivariate analysis, improved survival was associated with age <57 years (Hazard ratios [HR] 0.44, P = .012), lower comorbidity scores (HR 0.40, P = .008), surgical resection (HR 0.08, P < .001) and absence of lymph node metastasis (HR 0.23, P < .001). The 5-year overall survival was 87.1% for debulking surgery, 88.6% for radical resection and 26.6% for no surgical resection (P < .001). Lymph node metastases were associated with tumor size ≥5 cm (P = .006), malignant odontogenic histology (P = .025), and moderate/poor differentiation (P < .001). CONCLUSION: In this large series of odontogenic cancers, any type of surgical resection was associated with improved survival. Lymph node metastases, although infrequent, were associated with significantly worse survival. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 131:E1496-E1502, 2021.

Machine Learning-Guided Adjuvant Treatment of Head and Neck Cancer.

Importance: Postoperative chemoradiation is the standard of care for cancers with positive margins or extracapsular extension, but the benefit of chemotherapy is unclear for patients with other intermediate risk features. Objective: To evaluate whether machine learning models could identify patients with intermediate-risk head and neck squamous cell carcinoma who would benefit from chemoradiation. Design, Setting, and Participants: This cohort study included patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx from January 1, 2004, through December 31, 2016. Patients had resected disease and underwent adjuvant radiotherapy. Analysis was performed from October 1, 2019, through September 1, 2020. Patients were selected from the National Cancer Database, a hospital-based registry that captures data from more than 70% of newly diagnosed cancers in the United States. Three machine learning survival models were trained using 80% of the cohort, with the remaining 20% used to assess model performance. Exposures: Receipt of adjuvant chemoradiation or radiation alone. Main Outcomes and Measures: Patients who received treatment recommended by machine learning models were compared with those who did not. Overall survival for treatment according to model recommendations was the primary outcome. Secondary outcomes included frequency of recommendation for chemotherapy and chemotherapy benefit in patients recommended for chemoradiation vs radiation alone. Results: A total of 33 527 patients (24 189 [72%] men; 28 036 [84%] aged ≤70 years) met the inclusion criteria. Median follow-up in the validation data set was 43.2 (interquartile range, 19.8-65.5) months. DeepSurv, neural multitask logistic regression, and survival forest models recommended chemoradiation for 17 589 (52%), 15 917 (47%), and 14 912 patients (44%), respectively. Treatment according to model recommendations was associated with a survival benefit, with a hazard ratio of 0.79 (95% CI, 0.72-0.85; P < .001) for DeepSurv, 0.83 (95% CI, 0.77-0.90; P < .001) for neural multitask logistic regression, and 0.90 (95% CI, 0.83-0.98; P = .01) for random survival forest models. No survival benefit for chemotherapy was seen for patients recommended to receive radiotherapy alone. Conclusions and Relevance: These findings suggest that machine learning models may identify patients with intermediate risk who could benefit from chemoradiation. These models predicted that approximately half of such patients have no added benefit from chemotherapy.

Local Recurrence Following Total Marrow Radiation: Implications for Clinical Target Delineation.

Total marrow radiation is an emerging treatment modality used in patients undergoing stem cell transplantation. We present a rare case of a patient undergoing total marrow irradiation with concurrent ablative stem cell transplantation with local failures in two out-of-field areas that were not included in the clinical target volume A 31-year-old female patient initially presented with abdominal pain secondary to chronic myelogenous leukemia. She underwent dasatinib treatment for years, but subsequently developed recurrence and underwent consolidation systemic chemotherapy followed by allogeneic stem cell transplantation with adjuvant total marrow irradiation. Several months later, she noticed increased left jaw swelling and dysphagia with associated right ankle swelling. Biopsy of the right ankle and left mandible were consistent with recurrent myeloid sarcoma. This case report suggests that inclusion of the mandible and lower extremities may be necessary when performing total marrow radiation.

Risk Prediction Model Versus United States Preventive Services Task Force Lung Cancer Screening Eligibility Criteria: Reducing Race Disparities.

INTRODUCTION: Disparities exist in lung cancer outcomes between African American and white people. The current United States Preventive Services Task Force (USPSTF) lung cancer screening eligibility criteria, which is based solely on age and smoking history, may exacerbate racial disparities. We evaluated whether the PLCOm2012 risk prediction model more effectively selects African American ever-smokers for screening. METHODS: Lung cancer cases diagnosed between 2010 and 2019 at an urban medical center serving a racially and ethnically diverse population were retrospectively reviewed for lung cancer screening eligibility based on the USPSTF criteria versus the PLCOm2012 model. RESULTS: This cohort of 883 ever-smokers comprised the following racial and ethnic makeup: 258 white (29.2%), 497 African American (56.3%), 69 Hispanic (7.8%), 24 Asian (2.7%), and 35 other (4.0%). Compared with the USPSTF criteria, the PLCOm2012 model increased the sensitivity for the African American cohort at lung cancer risk thresholds of 1.51%, 1.70%, and 2.00% per 6 years (p < 0.0001). For example, at the 1.70% risk threshold, the PLCOm2012 model identified 71.3% African American cases, whereas the USPSTF criteria only identified 50.3% (p < 0.0001). In contrast, in case of whites there was no difference (66.0% versus 62.4%, respectively [p = 0.203]). Of the African American ever-smokers who were PLCO1.7%-positive and USPSTF-negative, the criteria missed from the USPSTF were those with pack-years less than 30 (67.7%), quit time of greater than 15 years (22.5%), and age less than 55 years (13.0%). CONCLUSIONS: The PLCOm2012 model was found to be preferable over the USPSTF criteria at identifying African American ever-smokers for lung cancer screening. The broader use of this model in racially diverse populations may help overcome disparities in lung cancer screening and outcomes.

Prostate Cancer Outcomes Following Solid-Organ Transplantation: A SEER-Medicare Analysis.

BACKGROUND: Immunosuppressive regimens associated with organ transplantation increase the risk of developing cancer. Transplant candidates and recipients with prostate cancer are often treated, even if low-risk features would ordinarily justify active surveillance. METHODS: Using SEER-Medicare, we identified 163 676 men aged 66 years and older diagnosed with nonmetastatic prostate cancer. History of solid organ transplant was identified using diagnosis or procedure codes. A propensity score-matched cohort was identified by matching transplanted men to nontransplanted controls by age, race, region, year, T-stage, grade, comorbidity, and cancer therapy. Fine-Gray competing risk models assessed associations between transplant status and prostate cancer-specific mortality (PCSM) and overall mortality (OM). RESULTS: We identified 620 men (0.4%) with transplant up to 10 years before (n = 320) or 5 years after (n = 300) prostate cancer diagnosis and matched them to 3100 men. At 10 years, OM was 55.7% and PCSM was 6.0% in the transplant cohort compared with 42.4% (P < .001) and 7.6% (P = .70) in the nontransplant cohort, respectively. Adjusted models showed no difference in PCSM for transplanted men (hazard ratio = 0.88, 95% confidence interval = 0.61 to 1.27, P = .70) or differences by prostate cancer therapy. Among 334 transplanted men with T1-2N0, well or moderately differentiated "low-risk" prostate cancer, PCSM was similar for treated and untreated men (hazard ratio = 0.92, 95% confidence interval = 0.47 to 1.81). CONCLUSIONS: Among men aged 66 years and older with prostate cancer, an organ transplant is associated with higher OM but no observable difference in PCSM. These findings suggest men with prostate cancer and previous or future organ transplantation should be managed per usual standards of care, including consideration of active surveillance for low-risk cancer characteristics.

Patterns of Care and Outcomes of Intensity-Modulated Radiotherapy and 3D Conformal Radiotherapy for Early Stage Glottic Cancer: A National Cancer Database Analysis.

Early stage glottic cancer has traditionally been treated with 3D conformal radiotherapy (3DCRT). However, intensity-modulated radiotherapy (IMRT) has been recently adopted as an alternative to decrease toxicity. Here, we compared the usage and outcomes of IMRT and 3DCRT for patients with early stage squamous cell carcinoma (SCC) of the glottic larynx. Using the National Cancer Database, we identified patients with Stage I-II SCC of the glottis who received 55-75 Gy using IMRT (n = 1623) or 3DCRT (n = 2696). Median follow up was 42 months with a 5-year overall survival (OS) of 72%. Using a nominal logistic regression, race, ethnicity, year of diagnosis and fraction size were associated with the receipt of IMRT (p < 0.05). Using Kaplan-Meier methods and Cox proportional hazards models as well as a propensity matched cohort, there was no difference in OS for patients who received IMRT versus 3DCRT (hazard ratio (HR), 1.08; 95% confidence interval (95% CI), 0.93-1.26; p = 0.302). However, there was a survival benefit for patients receiving slight hypofractionation as compared to conventional fractionation (HR, 0.78; 95% CI, 0.69-0.92; p = 0.003). IMRT was associated with similar survival as 3DCRT, supporting the implementation of this potentially less toxic modality without compromising survival.

Heart V5 predicts cardiac events in unresectable lung cancer patients undergoing chemoradiation.

BACKGROUND: Recent studies incorporating dose escalated radiation identified heart dose as a predictor of cardiac toxicity in unresectable lung cancer patients. Whether conventionally dosed radiation impacts cardiac events remains unclear. METHODS: Stage III lung cancer patients undergoing definitive chemoradiation to 60-70 Gy were analyzed. Clinical and dosimetric factors (mean heart dose, heart V5-60 in 5 Gy increments) were analyzed against freedom from ≥ grade 3 cardiac events and overall survival (OS) by log-rank test. Multivariable analysis (MVA) for factors significant on univariate analysis was performed by Cox proportional hazards. RESULTS: A total of 108 patients were identified. Median follow-up was 18.0 months. One- and two-year OS were 79% and 61%, respectively. On MVA, gross tumor volume (GTV) ≥98.6 cm3 [hazard ratio (HR): 2.11, 95% confidence interval (CI): 1.15-3.93, P=0.02] and female gender (HR: 2.01, 95% CI: 1.09-3.73, P=0.03) predicted for worse survival. Twelve patients (11%) developed ≥ grade 3 cardiac events. One- and two-year freedom from cardiac events (FFCE) was 94% and 84% respectively. On MVA, heart V5 ≥49% predicted for cardiac events (HR: 11.44, 95% CI: 1.31-111.60, P=0.03) while female gender was nearly significant (HR: 3.49, 95% CI: 0.97-16.80, P=0.06). Females presented with similar comorbidity scores, GTVs, and relapse rates but experienced higher heart doses than their male counterparts. CONCLUSIONS: Heart V5 ≥49% predicted for cardiac events after chemoradiation. However, cardiac dosimetry was not associated with survival. Rather, female gender and GTV ≥98.6 cm3 led to worse survival. This study corroborates emerging data that low-dose radiation to the heart impacts cardiac toxicity.