Biodistribution and Dosimetry of Intraventricularly Administered 124I-Omburtamab in Patients with Metastatic Leptomeningeal Tumors.

Radiation dose estimations are key for optimizing therapies. We studied the role of 124I-omburtamab (8H9) given intraventricularly in assessing the distribution and radiation doses before 131I-omburtamab therapy in patients with metastatic leptomeningeal disease and compared it with the estimates from cerebrospinal fluid (CSF) sampling. Methods: Patients with histologically proven malignancy and metastatic disease to the central nervous system or leptomeninges who met eligibility criteria for 131I-omburtamab therapy underwent immuno-PET imaging with 124I-8H9 followed by 131I-8H9 antibody therapy. Patients were imaged with approximately 74 MBq of intraventricular 124I-omburtamab via an Ommaya reservoir. Whole-body PET images were acquired at approximately 4, 24, and 48 h after administration and analyzed for dosimetry calculations. Peripheral blood and CSF samples were obtained at multiple time points for dosimetry estimation. Results: Forty-two patients with complete dosimetry and therapy data were analyzed. 124I-omburtamab PET-based radiation dosimetry estimations revealed mean (±SD) absorbed dose to the CSF for 131I-8H9 of 0.62 ± 0.40 cGy/MBq, compared with 2.22 ± 2.19 cGy/MBq based on 124I-omburtamab CSF samples and 1.53 ± 1.37 cGy/MBq based on 131I-omburtamab CSF samples. The mean absorbed dose to the blood was 0.051 ± 0.11 cGy/MBq for 124I-omburtamab samples and 0.07 ± 0.04 cGy/MBq for 131I-omburtamab samples. The effective whole-body radiation dose for 124I-omburtamab was 0.49 ± 0.27 mSv/MBq. The mean whole-body clearance half-time was 44.98 ± 16.29 h. Conclusion: PET imaging with 124I-omburtamab antibody administered intraventricularly allows for noninvasive estimation of dose to CSF and normal organs. High CSF-to-blood absorbed-dose ratios are noted, allowing for an improved therapeutic index to leptomeningeal disease and reduced systemic doses. PET imaging-based estimates were less variable and more reliable than CSF sample-based dosimetry.

Volumetric 3D assessment of ablation zones after thermal ablation of colorectal liver metastases to improve prediction of local tumor progression.

PURPOSE: The goal of this study was to develop and evaluate a volumetric three-dimensional (3D) approach to improve the accuracy of ablation margin assessment following thermal ablation of hepatic tumors. METHODS: The 3D margin assessment technique was developed to generate the new 3D assessment metrics: volumes of insufficient coverage (VICs) measuring volume of tissue at risk post-ablation. VICs were computed for the tumor and tumor plus theoretical 5- and 10-mm margins. The diagnostic accuracy of the 3D assessment to predict 2-year local tumor progression (LTP) was compared to that of manual 2D assessment using retrospective analysis of a patient cohort that has previously been reported as a part of an outcome-centered study. Eighty-six consecutive patients with 108 colorectal cancer liver metastases treated with radiofrequency ablation (2002-2012) were used for evaluation. The 2-year LTP discrimination power was assessed using receiver operating characteristic area under the curve (AUC) analysis. RESULTS: A 3D assessment of margins was successfully completed for 93 out of 108 tumors. The minimum margin size measured using the 3D method had higher discrimination power compared with the 2D method, with an AUC value of 0.893 vs. 0.790 (p = 0.01). The new 5-mm VIC metric had the highest 2-year LTP discrimination power with an AUC value of 0.923 (p = 0.004). CONCLUSIONS: Volumetric semi-automated 3D assessment of the ablation zone in the liver is feasible and can improve accuracy of 2-year LTP prediction following thermal ablation of hepatic tumors. KEY POINTS: • More accurate prediction of local tumor progression risk using volumetric 3D ablation zone assessment can help improve the efficacy of image-guided percutaneous thermal ablation of hepatic tumors. • The accuracy of evaluation of ablation zone margins after thermal ablation of colorectal liver metastases can be improved using a volumetric 3D semi-automated assessment approach and the volume of insufficient coverage assessment metric. • The new 5-mm volume-of-insufficient-coverage metric, indicating the volume of tumor plus 5-mm margin that remained untreated, had the highest 2-year local tumor progression discrimination power.

Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition.

PURPOSE: The objective of this study was to evaluate adverse events (AEs) in patients who received both immune checkpoint inhibitors and thoracic radiation therapy (RT). In particular, we compared the rate of toxicities of concurrent versus sequential delivery of thoracic RT and checkpoint inhibitors. METHODS AND MATERIALS: Patient and treatment characteristics were collected on all patients at our institution who were treated with programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors and underwent thoracic RT (n = 79). Receiving both treatments within 1 month was considered concurrent (n = 35; 44%), and any treatment up to 6 months apart was considered sequential (n = 44; 56%). The primary endpoint of this study was the rate of Grade ≥2 AEs from combination therapy (immunotherapy and RT), specifically those that are relevant to thoracic RT: Pneumonitis, other pulmonary events, esophagitis, dermatitis, and fatigue. Further univariate analysis was performed to compare AE rates with clinical and therapy-related variables. RESULTS: A total of 79 patients were identified, with lung cancer (n = 45) and melanoma (n = 15) being the most common primary histology. Sixty-two (78%) patients were treated with anti-PD-1 or anti-PD-L1 antibodies, 12 (15%) with anti-CTLA-4 antibodies, and 5 (6%) received both anti-PD-1/PD-L1 and anti-CTLA-4 antibodies. The median follow-up for survivors was 5.9 months (range, 2.4-55.6 months). Grade ≥2 AEs included pneumonitis (n = 5; 6%), esophagitis (n = 6; 8%), and dermatitis (n = 8; 10%). No statistically significant correlation was found between these AEs when comparing concurrent versus sequential treatment. The only significant variable was a correlation of immunotherapy drug category with Grade ≥2 esophagitis (P = .04). CONCLUSIONS: Overall, Grade ≥2 AE rates of thoracic RT and immunotherapy appeared as expected and acceptable. The lack of significant differences in AE rates with concurrent versus sequential treatment suggests that even concurrent immunotherapy and thoracic RT may be safe.

Stereotactic body radiation therapy (SBRT) improves local control and overall survival compared to conventionally fractionated radiation for stage I non-small cell lung cancer (NSCLC).

BACKGROUND: Stereotactic body radiotherapy (SBRT) has been adopted as the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC), with local control rates consistently >90%. However, data directly comparing the outcomes of SBRT with those of conventionally fractionated radiotherapy (CONV) is lacking. MATERIAL AND METHODS: Between 1990 and 2013, 497 patients (525 lesions) with early-stage NSCLC (T1-T2N0M0) were treated with CONV (n = 127) or SBRT (n = 398). In this retrospective analysis, five endpoints were compared, with and without adjusting for clinical and dosimetric factors. Competing risks analysis was performed to estimate and compare the cumulative incidence of local failure (LF), nodal failure (NF), distant failure (DF) and disease progression. Overall survival (OS) was estimated by the Kaplan-Meier method and compared by the Cox regression model. Propensity score (PS) matched analysis was performed based on seven patient and clinical variables: age, gender, Karnofsky performance status (KPS), histology, T stage, biologically equivalent dose (BED), and history of smoking. RESULTS: The median dose delivered for CONV was 75.6 Gy in 1.8-2.0 Gy fractions (range 60-90 Gy; median BED = 89.20 Gy) and for SBRT 48 Gy in four fractions (45-60 Gy in three to five fractions; median BED = 105.60 Gy). Median follow-up was 24.4 months, and 3-year LF rates were 34.1% with CONV and 13.6% with SBRT (p < .001). Three-year OS rates were 38.9 and 53.1%, respectively (p = .018). PS matching showed a significant improvement of OS (p = .0497) for SBRT. T stage was the only variable correlating with all five endpoints. CONCLUSION: SBRT compared to CONV is associated with improved LF rates and OS. Our data supports the continued use and expansion of SBRT as the standard of care treatment for inoperable early-stage NSCLC.

Long-term outcomes in oral cavity squamous cell carcinoma with adjuvant and salvage radiotherapy after surgery.

OBJECTIVE: Early-stage oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients, and locoregional recurrence rates are as high as 25% with surgery alone. Radiotherapy (RT) is typically reserved as part of salvage multimodality therapy after salvage surgery because it is generally thought that there is no significant detriment to salvage therapy. Our aim was to examine outcomes for recurrent OCSCC treated with salvage surgery and radiation and compare them to outcomes for patients treated with adjuvant postoperative RT upfront. METHODS: We identified 425 patients with OCSCC treated with postoperative RT at our institution. The 5-year rates of local failure, locoregional failure (LRF), survival, and distant metastasis (DM) were the main outcome measures. We performed a landmark analysis and examined the same outcomes in the adjuvant versus salvage cohorts using Cox proportional hazards and Fine-Gray competing risk method. RESULTS: The adjuvant cohort had higher tumor (T) (P < 0.0001) and nodal (N) (P < 0.0001) stage than the salvage cohort's stage at initial presentation. On multivariate analysis, a strategy of salvage RT experienced poorer overall survival (OS) compared to upfront adjuvant RT (hazard ratio [HR] 1.84; 95% confidence interval [CI], 1.26-2.70; P = 0.002). Moreover, salvage surgery followed by RT patients experienced increasing risk of LRF (HR 1.56; 95% CI, 1.18-2.06; P = 0.002) and (DM) (HR 1.53; 95% CI, 1.08-2.17; P = 0.02) on multivariate analysis. Additional analysis was performed excluding salvage cohort with advanced disease at initial presentation (T3-T4 and N2). Salvage RT treatment selection for early-stage OCSCC continued to experience significantly poorer OS as compared to adjuvant RT (HR 1.48; 95% CI, 1.002-2.19; P = 0.049). CONCLUSION: Early-stage OCSCC patients who are observed and experienced recurrence requiring salvage therapy (surgery and RT) have worse oncologic outcomes than locally advanced patients receiving upfront adjuvant RT. Prospective randomized studies are needed to identify high-risk subset of early-stage OCSCC comparing adjuvant RT versus observation, followed by salvage surgery and RT at recurrence. LEVEL OF EVIDENCE: 4. Laryngoscope, 2539-2545, 2018.

Outcome After Radiation Therapy for Langerhans Cell Histiocytosis Is Dependent on Site of Involvement.

PURPOSE: To characterize the efficacy and safety of radiation therapy in a contemporary Langerhans cell histiocytosis (LCH) cohort and to explore whether there are sites at higher risk for local recurrence. PATIENTS AND METHODS: Between 1995 and 2015 we identified 39 consecutive LCH patients who were treated primarily with radiation therapy. Patients were staged by single/multisystem involvement and established risk organ criteria. In 46 irradiated lesions, clinical and radiologic responses were evaluated at multiple time points after radiation therapy. Patient demographics, treatment, and local failure were compared by site of lesion. RESULTS: Median age at radiation therapy was 35 years (range, 1.5-67 years). Twelve patients had multisystem involvement, and of those, 5 patients had disease in organs considered to be high risk. The following sites were irradiated: bone (31), brain (6), skin (3), lymph node (3), thyroid (2), and nasopharynx (1). Median dose was 11.4 Gy (range, 7.5-50.4 Gy). At a median follow-up of 45 months (range, 6-199 months), local recurrence or progression was noted in 5 of 46 lesions (11%). There were no local failures of the 31 bone lesions evaluated, whereas the 3-year freedom from local failure in the 15 non-bone lesions was 63% (95% confidence interval 32-83%; P=.0008). Local failures occurred in 2 of 3 skin lesions, in 2 of 6 brain lesions, and 1 of 3 lymph node lesions. Deaths were recorded in 5 of 39 patients (13%), all of whom were adults with multisystem disease. CONCLUSION: Radiation therapy is a safe and effective measure for providing local control of LCH involving the bone. Whereas bone lesions are well controlled with low doses of radiation, disease in other tissues, such as the skin and brain, may require higher doses of radiation or additional treatment modalities.

Prostate-Specific Antigen (PSA) Bounce After Dose-Escalated External Beam Radiation Therapy Is an Independent Predictor of PSA Recurrence, Metastasis, and Survival in Prostate Adenocarcinoma Patients.

PURPOSE: To evaluate the difference in prostate-specific antigen (PSA) recurrence-free, distant metastasis-free, overall, and cancer-specific survival between PSA bounce (PSA-B) and non-bounce patients treated with dose-escalated external beam radiation therapy (DE-EBRT). METHODS AND MATERIALS: During 1990-2010, 1898 prostate adenocarcinoma patients were treated with DE-EBRT to ≥75 Gy with ≥5 years follow-up. Patients receiving neoadjuvant/concurrent androgen-deprivation therapy (n=1035) or with fewer than 4 PSA values obtained 6 months or more after post-EBRT completion (n=87) were excluded. The evaluable 776 patients were treated (median, 81.0 Gy). Prostate-specific antigen bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. Prostate-specific antigen relapse was defined as post-radiation therapy PSA nadir + 2 ng/mL. Median follow-up was 9.2 years (interquartile range, 6.9-11.3 years). RESULTS: One hundred twenty-three patients (15.9%) experienced PSA-B after DE-EBRT at a median of 24.6 months (interquartile range, 16.1-38.5 months). On multivariate analysis, younger age (P=.001), lower Gleason score (P=.0003), and higher radiation therapy dose (P=.0002) independently predicted PSA-B. Prostate-specific antigen bounce was independently associated with decreased risk for PSA relapse (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.33-0.85; P=.008), distant metastatic disease (HR 0.34; 95% CI 0.12-0.94; P=.04), and all-cause mortality (HR 0.53; 95% CI 0.29-0.96; P=.04) on multivariate Cox analysis. Because all 50 prostate cancer-specific deaths in patients without PSA-B were in the non-bounce cohort, competing-risks analysis was not applicable. A nonparametric competing-risks test demonstrated that patients with PSA-B had superior cancer-specific survival compared with patients without PSA-B (P=.004). CONCLUSIONS: Patients treated with dose-escalated radiation therapy for prostate adenocarcinoma who experience posttreatment PSA-B have improved PSA recurrence-free survival, distant metastasis-free survival, overall survival, and cancer-specific survival outcomes.

Identifying the Optimal Radiation Dose in Locally Advanced Non-Small-cell Lung Cancer Treated With Definitive Radiotherapy Without Concurrent Chemotherapy.

INTRODUCTION: The optimal radiation dose for locally advanced non-small-cell lung cancer (NSCLC) is not known for patients who receive sequential chemoradiation (CRT) or definitive radiotherapy (RT) only. Our objective was to determine whether a benefit exists for radiation dose escalation for these patients. MATERIALS AND METHODS: The patients included in our retrospective analysis had undergone RT for NSCLC from 2004 to 2013, had not undergone surgery, and received a dose ≥ 50.0 Gy. Patients who received concurrent CRT were excluded from the analysis, leaving 336 patients for analysis. The primary outcomes were overall survival (OS), local failure (LF), and distant failure (DF). RESULTS: On multivariate analysis, after adjusting for age, Karnofsky performance status, gross tumor volume, and treatment modality, patients treated with a radiation dose > 66 Gy had significantly improved OS compared with those treated with < 60 Gy (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.39-0.87; P = .008). After adjusting for smoking history and radiologic tumor size, patients treated with a radiation dose > 66 Gy had a significantly decreased risk of LF compared with those treated with < 60 Gy (HR, 0.59; 95% CI, 0.38-0.91; P = .02). The radiation dose was not an independent prognostic factor of DF on multivariate analysis. CONCLUSION: When controlling for tumor volume and/or dimensions and other independent prognostic factors, patients with locally advanced NSCLC who were not candidates for concurrent CRT benefited from a radiation dose > 66 Gy versus < 60 Gy with improved OS and reduced LF. An increased radiation dose did not appear to affect the incidence of DF.

Trends and variations in postmastectomy radiation therapy for breast cancer in patients with 1 to 3 positive lymph nodes: A National Cancer Data Base analysis.

BACKGROUND: High-level evidence is lacking to guide treatment decisions about postmastectomy radiation therapy (PMRT) in patients who have breast cancer with 1 to 3 positive lymph nodes who receive contemporary systemic therapies, leading to potential variations in PMRT delivery. The objective of this study was to examine nationwide trends in PMRT use in this group. METHODS: The National Cancer Data Base (NCDB) was used to identify 93,372 women who had T1-T2N1 breast cancer diagnosed between 2003 and 2012. Patients who received neoadjuvant chemotherapy or radiation therapy (RT) and those who had bilateral breast cancers were excluded. Time trends were evaluated using the Cochrane-Armitage test and correlated the receipt of PMRT with various patient demographic, facility, clinicopathologic, and treatment variables using multivariable logistic regression. A second analysis was performed for patients who were diagnosed during 2010 and included radiation oncologist density as an additional covariate. P values < .0001 were considered statistically significant. RESULTS: Overall, 22.5% of the study population received PMRT, representing an increase from 19.1% in 2003 to 30.3% in 2012. Factors associated with greater PMRT use included younger age, lower Charlson-Deyo comorbidity scores, shorter distance to the treating facility, treatment at a comprehensive cancer program, facility location in the New England Census division, and higher density of radiation oncologists. Increased PMRT use was associated with later year of diagnosis, receipt of chemotherapy, receipt of hormone therapy, higher grade disease, larger tumor size, greater numbers of positive lymph nodes, positive margins, and absence of immediate breast reconstruction (all P < .0001). CONCLUSIONS: The receipt of PMRT by patients with breast cancer who have 1 to 3 positive lymph nodes has increased over time, with wide variability in practice patterns in the United States. Cancer 2018;124:482-90. © 2017 American Cancer Society.

Factors influencing the utilization of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer.

PURPOSE: Brain metastases are common in patients with limited-stage small cell lung cancer (LS-SCLC) due to the inability of most chemotherapeutics to penetrate the blood-brain barrier. Prophylactic cranial irradiation (PCI) is therefore recommended for use in patients with a good response to concurrent chemoradiotherapy. However, PCI is not always delivered; therefore, we investigated the reasons for PCI omission in patients who underwent therapy with curative intent. METHODS AND MATERIALS: We retrospectively reviewed all patients with LS-SCLC who were treated with curative intent at our institution. Overall survival and cumulative incidence of brain metastasis were estimated by the Kaplan-Meier method. The Pearson χ2 test and Mann-Whitney U test were used to examine factors associated with PCI use, and prognostic factors were analyzed with Cox proportional hazards modeling. RESULTS: We examined 208 patients who were treated for LS-SCLC at our institution. A total of 115 patients (55%) received PCI. The most common documented reason for PCI omission was patient refusal due to neurotoxicity concerns (38%). Physician assessment of being medically unfit (33%) and of advanced age (8%) were the second and third most common reasons, respectively. Karnofsky performance status and clinical American Joint Committee on Cancer stage but not PCI were significantly associated with overall survival. Only clinical stage remained an independent factor on multivariate analysis. CONCLUSIONS: Approximately half of patients with LS-SCLC ultimately receive PCI, generally for guideline-recommended reasons. The most common reason for PCI omission was patient concerns regarding neurotoxicity. Efforts to decrease PCI neurotoxicity, including hippocampal-sparing radiation and memantine use, may increase the use of this survival-improving intervention in eligible patients with LS-SCLC.

A Descriptive Report of Early Mobilization for Critically Ill Ventilated Patients with Cancer.

BACKGROUND: Early mobilization protocols have been successfully implemented to improve function in critically ill patients; however, no study has focused on the oncology population. OBJECTIVES: To investigate the feasibility of early mobilization and describe the rehabilitation interventions and discharge outcomes in a cohort of critically ill patients with cancer. DESIGN: Retrospective review. METHODS: A retrospective analysis of patients with cancer who participated in occupational and physical therapy while on mechanical ventilation utilizing an institutional early mobilization protocol from June 2010 - July 2011, was completed. Demographic and clinical variables were abstracted, as well as occupational and physical therapy interventions. RESULTS: A cohort of 42 cancer patients on mechanical ventilation in the mixed medical/surgical intensive care unit of a comprehensive cancer center received early mobilization during the study period. The majority of participants demonstrated improved cognitive and functional status from the intensive care unit to hospital discharge. There were no reported adverse events during the occupational and physical therapy sessions. Among the 30 hospital survivors, 53% required continued rehabilitation services in their home environment and 40% were transferred to a rehabilitation facility. LIMITATIONS: Due to the small sample size, these findings are not generalizable to all critically ill cancer patients. There was no post-acute care follow-up of cognitive and physical functional performance. CONCLUSION: Early mobilization appears feasible in addressing the cognitive and functional needs of oncology patients in the intensive care unit.

Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for unresectable pancreatic cancer, and is postulated to be more effective and less toxic than conventionally fractionated intensity modulated radiation therapy (IMRT). MATERIAL AND METHODS: We retrospectively reviewed unresectable stage I-III pancreatic adenocarcinoma treated from 2008 to 2016 at our institution with SBRT (five fractions, 30-33 Gy) or IMRT (25-28 fractions, 45-56 Gy with concurrent chemotherapy). Groups were compared with respect to overall survival (OS), local and distant failure, and toxicity. Log-rank test and Cox proportional hazards regression model, and competing risks methods were used for univariate and multivariate analysis. RESULTS: SBRT patients (n = 44) were older than IMRT (n = 226) patients; otherwise there was no significant difference in baseline characteristics. There was no significant difference in OS or local or distant failure. There was no significant difference in rates of subsequent resection (IMRT =17%, SBRT =7%, p = .11). IMRT was associated with more acute grade 2+ gastrointestinal toxicity, grade 2+ fatigue, and grade 3+ hematologic toxicity (p = .008, p < .0001, p = .001, respectively). CONCLUSIONS: In this analysis, SBRT achieves similar disease control outcomes as IMRT, with less acute toxicity. This suggests SBRT is an attractive technique for pancreatic radiotherapy because of improved convenience and tolerability with equivalent efficacy. However, the lack of observed advantages in disease control with this moderate-dose SBRT regimen may suggest a role for increasing SBRT dose, if this can be accomplished without significant increase in toxicity.

Protective Lung Ventilation and Morbidity After Pulmonary Resection: A Propensity Score-Matched Analysis.

BACKGROUND: Protective lung ventilation (PLV) during one-lung ventilation (OLV) for thoracic surgery is frequently recommended to reduce pulmonary complications. However, limited outcome data exist on whether PLV use during OLV is associated with less clinically relevant pulmonary morbidity after lung resection. METHODS: Intraoperative data were prospectively collected in 1080 patients undergoing pulmonary resection with OLV, intentional crystalloid restriction, and mechanical ventilation to maintain inspiratory peak airway pressure <30 cm H2O. Other ventilator settings and all aspects of anesthetic management were at the discretion of the anesthesia care team. We defined PLV and non-PLV as <8 or ≥8 mL/kg (predicted body weight) mean tidal volume. The primary outcome was the occurrence of pneumonia and/or acute respiratory distress syndrome (ARDS). Propensity score matching was used to generate PLV and non-PLV groups with comparable characteristics. Associations between outcomes and PLV status were analyzed by exact logistic regression, with matching as cluster in the anatomic and nonanatomic lung resection cohorts. RESULTS: In the propensity score-matched analysis, the incidence of pneumonia and/or ARDS among patients who had an anatomic lung resection was 9/172 (5.2%) in the non-PLV compared to the PLV group 7/172 (4.1%; odds ratio, 1.29; 95% confidence interval, 0.48-3.45, P= .62). The incidence of pneumonia and/or ARDS in patients who underwent nonanatomic resection was 3/118 (2.5%) in the non-PLV compared to the PLV group, 1/118 (0.9%; odds ratio, 3.00; 95% confidence interval, 0.31-28.84, P= .34). CONCLUSIONS: In this prospective observational study, we found no differences in the incidence of pneumonia and/or ARDS between patients undergoing lung resection with tidal volumes <8 or ≥8 mL/kg. Our data suggest that when fluid restriction and peak airway pressures are limited, the clinical impact of PLV in this patient population is small. Future randomized trials are needed to better understand the benefits of a small tidal volume strategy during OLV on clinically important outcomes.

Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma.

INTRODUCTION: Higher target conformity and better sparing of organs at risk with modern radiotherapy (RT) may result in higher tumor control and less toxicity. In this study, we compare our institutional multimodality therapy experience of adjuvant chemotherapy and hemithoracic intensity-modulated pleural RT (IMPRINT) with previously used adjuvant conventional RT (CONV) in patients with malignant pleural mesothelioma (MPM) treated with lung-sparing pleurectomy/decortication (P/D). METHODS: We analyzed 209 patients who underwent P/D and adjuvant RT (131 who received CONV and 78 who received IMPRINT) for MPM between 1974 and 2015. The primary end point was overall survival (OS). The Kaplan-Meier method and Cox proportional hazards model were used to calculate OS; competing risks analysis was performed for local failure-free survival and progression-free survival. Univariate analysis and multivariate analysis were performed with relevant clinical and treatment factors. RESULTS: The median age was 64 years, and 80% of the patients were male. Patients receiving IMPRINT had significantly higher rates of the epithelial histological type, advanced pathological stage, and chemotherapy treatment. OS was significantly higher after IMPRINT (median 20.2 versus 12.3 months, p = 0.001). Higher Karnofsky performance score, epithelioid histological type, macroscopically complete resection, and use of chemotherapy/IMPRINT were found to be significant factors for longer OS in multivariate analysis. No significant predictive factors were identified for local failure or progression. Grade 2 or higher esophagitis developed in fewer patients after IMPRINT than after CONV (23% versus 47%). CONCLUSIONS: Trimodality therapy including adjuvant hemithoracic IMPRINT, chemotherapy, and P/D is associated with promising OS rates and decreased toxicity in patients with MPM. Dose constraints should be applied vigilantly to minimize serious adverse events.

Preoperative Echocardiographic Indices of Diastolic Dysfunction and Brain Natriuretic Peptide in Predicting Postoperative Atrial Fibrillation After Noncardiac Surgery.

BACKGROUND: We have shown previously that either echocardiographic indices of diastolic dysfunction or increased preoperative brain natriuretic peptide (BNP) predict postoperative atrial fibrillation (POAF). Because these 2 predictors of POAF have not been evaluated together, our goal was to further elucidate their concurrent role in patients undergoing noncardiac thoracic surgery. METHODS: We retrospectively identified 191 patients who had a preoperative transthoracic echocardiogram and serum BNP level collected as part of routine care before major lung or esophageal resection. Clinical and echocardiographic data were compared between patients who did or did not develop POAF (>5 minutes), and prognostic factors for POAF were identified. RESULTS: Univariate associations with POAF (41 of 191; 22% patients) included older age (P = .04), male sex (P = .01), hypertension (P = .03), increased body mass index (P = .01), and prolonged transmitral flow deceleration time (P < .0001), whereas BNP was not statistically significant (P = .07). Stepwise logistic regression analysis showed that both increasing transmitral flow deceleration time (continuous data log base 2 transformed; odds ratio, 16.05; 95% confidence interval, 3.74-68.96; P = .0002) and left atrial diastolic volume index (continuous data log base 2 transformed; odds ratio, 3.29; 95% confidence interval, 1.22-8.91; P = .02) were independent risk factors of POAF (area under the receiver operating characteristic curve = 0.73). There was no significant interaction between BNP and the 2 independent variables (P = .60, and P = .90), respectively. CONCLUSIONS: In a cohort of patients who had echocardiography and BNP measurements before undergoing major thoracic surgery, this study showed that when evaluated together greater preoperative left atrial diastolic volume index and transmitral flow deceleration time but not BNP levels were independent predictors for POAF.

Comparison of compressed sensing diffusion spectrum imaging and diffusion tensor imaging in patients with intracranial masses.

PURPOSE: To compare compressed diffusion spectrum imaging (CS-DSI) with diffusion tensor imaging (DTI) in patients with intracranial masses. We hypothesized that CS-DSI would provide superior visualization of the motor and language tracts. MATERIALS AND METHODS: We retrospectively analyzed 25 consecutive patients with intracranial masses who underwent DTI and CS-DSI for preoperative planning. Directionally-encoded anisotropy maps, and streamline hand corticospinal motor tracts and arcuate fasciculus language tracts were graded according to a 3-point scale. Tract counts, anisotropy, and lengths were also calculated. Comparisons were made using exact marginal homogeneity, McNemar's and Wilcoxon signed-rank tests. RESULTS: Readers preferred the CS-DSI over DTI anisotropy maps in 92% of the cases, and the CS-DSI over DTI tracts in 84%. The motor tracts were graded as excellent in 80% of cases for CS-DSI versus 52% for DTI; 58% of the motor tracts graded as acceptable in DTI were graded as excellent in CS-DSI (p=0.02). The language tracts were graded as excellent in 68% for CS-DSI versus none for DTI; 78% of the language tracts graded as acceptable by DTI were graded as excellent by CS-DSI (p<0.001). CS-DSI demonstrated smaller normalized mean differences than DTI for motor tract counts, anisotropy and language tract counts (p≤0.01). CONCLUSION: CS-DSI was preferred over DTI for the evaluation of motor and language white matter tracts in patients with intracranial masses. Results suggest that CS-DSI may be more useful than DTI for preoperative planning purposes.

Chemotherapy and intensity-modulated radiation therapy for locally advanced pancreatic cancer achieves a high rate of R0 resection.

BACKGROUND: To assess local control, survival and conversion to resectability among locally advanced pancreatic cancer (LAPC) patients treated with induction chemotherapy (ICT) followed by chemoradiotherapy treatment using intensity-modulated radiation therapy (IMRT). MATERIAL AND METHODS: Between 2007 and 2012, 134 LAPC patients were treated with ICT followed by IMRT. After chemoradiotherapy, 40 patients received maintenance chemotherapy. RESULTS: With a median follow-up of 20 months, median overall survival (OS) was 23 months. One- and two-year OS was 85% and 47%, respectively. On multivariate analysis, progression of disease after IMRT was associated with worse OS. Cumulative incidence of local failure was 10% at one year and 36% at two years. Twenty-six patients (19%) underwent resection after chemoradiotherapy including 22 patients (85%) with negative margins. On multivariate analysis, response to IMRT was associated with surgery (p = .01). Acute grade 3-4 hematologic and non-hematologic toxicity rates were 26% and 4.5%, respectively. CONCLUSION: IMRT is safe in patients with LAPC. Patients with non-progressive LAPC after ICT and who received IMRT had high rates of local control and prolonged survival.

PIK3CA mutation is associated with increased local failure in lung stereotactic body radiation therapy (SBRT).

OBJECTIVES: Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway has been associated with radioresistance. It is unclear whether such mutations confer suboptimal local control for patients who receive lung stereotactic body radiation therapy (SBRT). Our objective was to examine whether mutations in the EGFR/AKT/PIK3CA signaling pathway are associated with local failure (LF) after lung SBRT. METHODS: We retrospectively reviewed 166 patients who underwent SBRT to primary or metastatic lung lesions from 2007-2015 for whom genetic testing data was available for EGFR, AKT, and PIK3CA genes. Association between clinical factors, including molecular mutation status, and LF was evaluated. RESULTS: Six patients (4%) had PIK3CA mutation, 36 patients (22%) had EGFR mutation, and one patient (0.6%) had AKT1 mutation. Median lesion size was 2.0 cm (range, 0.6-5.6 cm); median dose was 48Gy in 4 fractions (range, 30-70Gy in 3-10 fractions). Median follow-up for survivors was 27.3 months (range, 3.8-66.7 months). LF occurred in 16 patients (10%). On univariate analysis, PIK3CA mutation was associated with LF (HR 10.44 [95% CI 2.16-50.46], p=0.003), while tumor histology, tumor size, primary tumor site, BED and EGFR mutation were not. At one year, probability of LF in lesions with PIK3CA mutation was 20.0% vs. 2.9% in lesions without mutation (p<0.001 by log rank test). CONCLUSION: Although the number of patients affected was small, PIK3CA mutation was significantly associated with higher risk of LF in patients undergoing lung SBRT. This association has not previously been reported for lung SBRT and indicates the need for further validation.

Concurrent Chemoradiotherapy With Cisplatin Versus Cetuximab for Squamous Cell Carcinoma of the Head and Neck.

OBJECTIVES: We previously reported inferior outcomes for locally advanced head and neck cancer treated with cetuximab (C225) versus cisplatin (CDDP). We now examine if this difference persists when accounting for HPV status and update outcomes on the entire cohort. MATERIALS AND METHODS: From 3/106 to 4/1/08, 174 locally advanced head and neck cancer patients received definitive treatment with RT and CDDP (n=125) or RT and C225 (n=49). Of these, 62 patients had tissue available for HPV analysis. RESULTS: The median follow-up was 47 months. The 3-year loco-regional failure, disease-free survival, and overall survival for CDDP versus C225 were 5.7% versus 40.2% (P<0.0001), 85.1% versus 35.4% (P<0.0001), and 90.0% versus 56.6% (P<0.0001), respectively. In the subset with tissue, there was no difference in rates of HPV or p16 positivity between the 2 groups. In this subset, the 3-year loco-regional failure, disease-free survival, and overall survival for CDDP versus C225 were 5.3% versus 32.0% (P=0.01), 86.8% versus 43.2% (P=0.002), and 86.7% versus 76.9% (P=0.09), respectively. Multivariate analysis continued to show a benefit for CDDP. CONCLUSIONS: With longer follow-up and the inclusion of HPV and p16 status for about one third of patients where tissue was available, we continued to find superior outcomes with concurrent CDDP versus C225.

Long-term Impact of Androgen-deprivation Therapy on Cardiovascular Morbidity After Radiotherapy for Clinically Localized Prostate Cancer.

OBJECTIVE: To characterize the impact of androgen-deprivation therapy (ADT) on the incidence of cardiovascular events (CE) in prostate cancer patients treated with radiotherapy (RT). MATERIALS AND METHODS: There were 2211 patients with localized prostate cancer treated with RT from 1988 to 2008 at our institution. There were 991 patients (44.8%) who received ADT at the time of RT for a median of 6.1 months. Salvage ADT was initiated prior to CE in 365 men (16.5%) at a median of 5.5 years (range: 0.6 to 18.4 years) after RT and continued for a median of 4.3 years. A nomogram was constructed to predict the 10-year risk of CE "post-RT" (i.e., after RT). RESULTS: Patients receiving ADT at the time of RT exhibited significantly higher 10-year incidence of CE (19.6%, 95% CI 17.0%-22.6%) than those not receiving ADT (14.3%, 95% CI 12.2%-16.7%, P = .005). On multivariate analysis, both ADT at the time of RT (P = .007) and the time of salvage (P = .0004) were associated with increased CE risk, as were advanced age (P = .02), smoking (P = .0007), history of diabetes (P = .0007), and history of CE before RT (P < .0001). A nomogram using patient age, smoking status, history of pre-RT CE, history of diabetes, and ADT use at the time of RT predicted the rate of 10-year CE with a C-index of 0.81 (95% CI, 0.72-0.88). CONCLUSION: While ADT is often an essential part of prostate cancer treatment, patients should be counseled regarding increased risks of CE and prophylactic efforts should be considered to mitigate that risk.