Financial Strain, Mental Illness, and Homelessness: Results From a National Longitudinal Study.

BACKGROUND: Research indicates that adults with severe mental illness have lower income and employment than adults without severe mental illness. Further, mental illness has been identified as a risk factor for homelessness. However, little research has investigated the interrelationships between financial strain, mental illness, and homelessness. It is unknown whether or to what extent financial strain mediates the association between mental illness and subsequent homelessness. METHODS: This study examined financial strain and severe mental illness (psychotic, bipolar, and depressive disorders in the past 12 months) as predictors of subsequent homelessness and financial strain as a mediator of the link between severe mental illness and homelessness by analyzing data from waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (n=34,653). RESULTS: χ2 and multivariable analyses revealed that financial crises and debt, lower income, unemployment, and past homelessness at wave 1 each significantly predicted subsequent homelessness between waves 1 and 2. For participants with and without severe mental illness, risk of homelessness between waves 1 and 2 increased as a function of the number of financial strain variables at wave 1. Mediation analyses showed a direct effect of severe mental illness on future homelessness as well as an indirect effect via greater financial strain, which accounted for 39% of the link between mental illness and homelessness. CONCLUSIONS: The findings showing that financial strain mediated the association between severe mental illness and homelessness support assessment of financial well-being in the context of treatment of mental illness and homeless service programs. The results suggest that individuals experiencing homelessness who have severe mental illness may benefit from assistance increasing financial literacy, improving money management, and achieving financial well-being.

Incorporation of extracorporeal photopheresis into a reduced intensity conditioning regimen in myelodysplastic syndrome and aggressive lymphoma: results from ECOG 1402 and 1902.

BACKGROUND: Extracorporeal photopheresis (ECP) is an immunomodulatory cellular therapy which has been shown to induce a tolerogenic state in patients with acute and chronic graft-vs-host disease. ECOG-ACRIN explored the activity of ECP as a part of a reduced intensity conditioning regimen in two multicenter trials in patients with MDS (E1902) and lymphomas (E1402). While both studies closed before completing accrual, we report results in 23 patients (17 MDS and 6 lymphoma). STUDY DESIGN AND METHODS: Patients received 2 days of ECP followed by pentostatin 4 mg/m2 /day for two consecutive days, followed by 600 cGy of total body irradiation prior to stem cell infusion. Immunosuppression for aGVHD was infusional cyclosporine A or tacrolimus and methotrexate on day +1, +3, with mycophenolate mofetil starting on day 100 for chronic GVHD prophylaxis. RESULTS: All patients engrafted, with median time to neutrophil and platelet engraftment of 15-18 days and 10-18 days respectively. Grade 3 or 4 aGVHD occurred in 13% and chronic extensive GVHD in 30%. CONCLUSIONS: These studies demonstrate that ECP/pentostatin/TBI is well tolerated and associated with adequate engraftment of neutrophils and platelets in patients with lymphomas and MDS.

The central role of disgust in disorders of food avoidance.

BACKGROUND: Individuals with extreme food avoidance such as Avoidant Restrictive Food Intake Disorder (ARFID) experience impairing physical and mental health consequences from nutrition of insufficient variety or/and quantity. Identifying mechanisms contributing to food avoidance is essential to develop effective interventions. Anxiety figures prominently in theoretical models of food avoidance; however, there is limited evidence that repeated exposures to foods increases approach behavior in ARFID. Studying disgust, and relationships between disgust and anxiety, may offer novel insights, as disgust is functionally associated with avoidance of contamination from pathogens (as may occur via ingestion) and is largely resistant to extinction. METHOD: This exploratory, cross-sectional study included data from 1,644 adults who completed an online questionnaire. Participant responses were used to measure ARFID classification, picky eating, sensory sensitivity, disgust, and anxiety. Structural equation modeling tested a measurement model of latent disgust and anxiety factors as measured by self-reported frequency of disgust and anxiety reactions. Mediational models were used to explore causal ordering. RESULTS: A latent disgust factor was more strongly related to severity of picky eating (B ≈ 0.4) and ARFID classification (B ≈ 0.6) than the latent anxiety factor (B ≈ 0.1). Disgust partially mediated the association between anxiety and picky eating and fully mediated the association between anxiety and ARFID. Models testing the reverse causal ordering demonstrated poorer fit. Findings suggest anxiety may be associated with food avoidance in part due to increased disgust. CONCLUSIONS: Disgust may play a prominent role in food avoidance. Findings may inform novel approaches to treatment.

The Clinical Significance of Posterior Insular Volume in Adolescent Anorexia Nervosa.

OBJECTIVE: The diagnostic criterion disturbance in the experience of the body remains a poorly understood and persistent feature of anorexia nervosa (AN). Increased sophistication in understanding the structure of the insular cortex-a neural structure that receives and integrates visceral sensations with action and meaning-may elucidate the nature of this disturbance. We explored age, weight status, illness severity, and self-reported body dissatisfaction associations with insular cortex volume. METHODS: Structural magnetic resonance imaging data were collected from 21 adolescents with a history of AN and 20 age-, sex-, and body mass index-matched controls. Insular cortical volumes (bilateral anterior and posterior regions) were identified using manual tracing. RESULTS: Volumes of the right posterior insula demonstrated the following: (a) a significant age by clinical status interaction (ß = -0.018 [0.008]; t = 2.32, p = .02) and (b) larger volumes were associated with longer duration of illness (r = 0.48, p < .04). In contrast, smaller volumes of the right anterior insula were associated with longer duration of illness (r = -0.50, p < .03). The associations of insular volume with body dissatisfaction were of moderate effect size and also of opposite direction, but a statistical trend in right posterior (r = 0.40, p < .10 in right posterior; r = -0.49, p < .04 in right anterior). CONCLUSIONS: In this exploratory study, findings of atypical structure of the right posterior insular cortex point to the importance of future work investigating the role of visceral afferent signaling in understanding disturbance in body experience in AN.

A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402.

Patients with early stage diffuse large B-cell lymphoma (DLBCL) receive RCHOP (rituximab cyclophosphamide, doxorubicin, vincristine, prednisone) alone or with involved field radiotherapy (IFRT). Anti-CD20 radioimmunotherapy (RIT) delivers radiation to microscopic sites outside of known disease. This phase II study aimed to achieve a functional complete response (CR) rate of ≥75% to RCHOP and (90) Yttrium-ibritumomab tiuxetan RIT. Patients with stages I/II DLBCL received 4-6 cycles of RCHOP followed by RIT [14·8 MBq/kg (0·4 mCi/kg)]; patients with positron emission tomographypositive sites of disease after RCHOP/RIT received 30 Gy IFRT. Of the 62 patients enrolled; 53 were eligible. 42% (22/53) had stage I/IE; 58% (31/53) stage II/IIE. After RCHOP, 79% (42/53) were in CR/unconfirmed CR. Forty-eight patients proceeded to RIT. One partial responder after RIT received IFRT and achieved a CR. The best response after RCHOP + RIT in all 53 patients was a functional CR rate of 89% (47/53; 95% confidence interval: 77-96%). With a median follow-up of 5·9 years, 7 (13%) patients have progressed and 4 (8%) have died (2 with DLBCL). At 5 years, 78% of patients remain in remission and 94% are alive. Chemoimmunotherapy and RIT is an active regimen for early stage DLBCL patients. Eighty-nine percent of patients achieved functional CR without the requirement of IFRT. This regimen is worthy of further study for early stage DLBCL in a phase III trial.

Evaluation of the International Prognostic Score (IPS-7) and a Simpler Prognostic Score (IPS-3) for advanced Hodgkin lymphoma in the modern era.

The International Prognostic Score (IPS-7) is the most commonly used risk stratification tool for advanced Hodgkin lymphoma (HL), however recent studies suggest the IPS-7 is less discriminating due to improved outcomes with contemporary therapy. We evaluated the seven variables for IPS-7 recorded at study entry for 854 patients enrolled on Eastern Cooperative Oncology Group 2496 trial. Univariate and multivariate Cox models were used to assess their prognostic ability for freedom from progression (FFP) and overall survival (OS). The IPS-7 remained prognostic however its prognostic range has narrowed. On multivariate analysis, two factors (age, stage) remained significant for FFP and three factors (age, stage, haemoglobin level) for OS. An alternative prognostic index, the IPS-3, was constructed using age, stage and haemoglobin level, which provided four distinct risk groups [FFP (P = 0·0001) and OS (P < 0·0001)]. IPS-3 outperformed the IPS-7 on risk prediction for both FFP and OS by model fit and discrimination criteria. Using reclassification calibration, 18% of IPS-7 low risk patients were re-classified as intermediate risk and 13% of IPS-7 intermediate risk patients as low risk. For patients with advanced HL, the IPS-3 may provide a simpler and more accurate framework for risk assessment in the modern era. Validation of these findings in other large data sets is planned.

Should all patients with SCLC receive prophylactic cranial irradiation if they have responded to treatment? The time has come to improve on a former standard.

Brain metastases are common in patients with small cell lung cancer (SCLC), and prophylactic cranial irradiation (PCI) has been shown to reduce the risk of brain metastases in these patients. But how great are the benefits, and do the benefits outweigh the toxicity? In this month's Counterpoints, Dr Ben J. Slotman makes the case for the use of PCI in nearly all patients with SCLC who have responded to treatment, whereas Jacob Yousef and Dr Henry Wagner argue that the role of PCI should be reassessed.

The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496.

There is a lack of contemporary prospective data examining the adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) and Stanford V (SV; doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone) regimens in older Hodgkin lymphoma (HL) patients. Forty-four advanced-stage, older HL patients (aged ≥60 years) were treated on the randomized study, E2496. Toxicities were mostly similar between chemotherapy regimens, although 24% of older patients developed bleomycin lung toxicity (BLT), which occurred mainly with ABVD (91%). Further, the BLT-related mortality rate was 18%. The overall treatment-related mortality for older HL patients was 9% vs. 0·3% for patients aged <60 years (P < 0·001). Among older patients, there were no survival differences between ABVD and SV. According to age, outcomes were significantly inferior for older versus younger patients (5-year failure-free survival: 48% vs. 74%, respectively, P = 0·002; 5-year overall survival: 58% and 90%, respectively, P < 0·0001), although time-to-progression (TTP) was not significantly different (5-year TTP: 68% vs. 78%, respectively, P = 0·37). Furthermore, considering progression and death without progression as competing risks, the risk of progression was not different between older and younger HL patients (5 years: 30% and 23%, respectively, P = 0·30); however, the incidence of death without progression was significantly increased for older HL patients (22% vs. 9%, respectively, P < 0·0001). Altogether, the marked HL age-dependent survival differences appeared attributable primarily to non-HL events.

Homelessness and money mismanagement in Iraq and Afghanistan veterans.

OBJECTIVES: We examined the empirical link between money mismanagement and subsequent homelessness among veterans. METHODS: We used a random sample of Iraq and Afghanistan War era veterans from the National Post-Deployment Adjustment Survey in 2009-2011. RESULTS: Veterans were randomly selected from a roster of all US military service members in Operation Iraqi Freedom or Operation Enduring Freedom who were separated from active duty or in the Reserves/National Guard. Veterans (n = 1090) from 50 states and all military branches completed 2 waves of data collection 1 year apart (79% retention rate). Thirty percent reported money mismanagement (e.g., bouncing or forging a check, going over one's credit limit, falling victim to a money scam in the past year). Multivariate analysis revealed money mismanagement (odds ratio [OR] = 4.09, 95% CI = 1.87, 8.94) was associated with homelessness in the next year, as were arrest history (OR = 2.65, 95% CI = 1.33, 5.29), mental health diagnosis (OR = 2.59, 95% CI = 1.26, 5.33), and income (OR = 0.30, 95% CI = 0.13, 0.71). CONCLUSIONS: Money mismanagement, reported by a substantial number of veterans, was related to a higher rate of subsequent homelessness. The findings have implications for policymakers and clinicians, suggesting that financial education programs offered by the US Departments of Defense and Veterans Affairs may be targeted to effectively address veteran homelessness.

Perception of affect in biological motion cues in anorexia nervosa.

OBJECTIVE: Nonverbal motion cues (a clenched fist) convey essential information about the intentions of the actor. Individuals with anorexia nervosa (AN) have demonstrated impairment in deciphering intention from facial affective cues, but it is unknown whether such deficits extend to deciphering affect from body motion cues. METHOD: We examined the capacities of adults with AN (n = 21) or those weight restored for ≥12 months (WR; n = 20) to perceive affect in biological motion cues relative to healthy controls (HC; n = 23). RESULTS: Overall, individuals with AN evidenced greater deficit in discriminating affect from biological motion cues than WR or HC. Follow-up analyses showed that individuals with AN differed especially across two of the five conditions--deviating most from normative data when discriminating sadness and more consistently discriminating anger relative to WR or HC. DISCUSSION: Implications of these findings are discussed in relation to some puzzling interpersonal features of AN.

The role of trauma, social support, and demography on veteran resilience.

Background: Historically, resilience has often been conceptualized as the sustained lack of symptoms following trauma exposure. In line with a novel conceptualization of resilience as being dynamic over lifespan, determined by interacting biological and environmental factors, we examined the VA Mid-Atlantic Post Deployment Mental Health Repository (PDMH) comprised of 3876 US Military Veterans with and without PTSD diagnoses. Methods: We performed regression modelling to study the relationship between resilience (measured with Connor Davidson Resilience Scale; CD-RISC), posttraumatic stress disorder (PTSD) severity (Davidson Trauma Scale; DTS), social support (Medical Outcome Study Social Support Survey; MOSSS), combat exposure (Combat Exposure Scale; CES), childhood trauma (Trauma Life Events Questionnaire; TLEQ), and demographic factors. CD-RISC was positively correlated with years of education and negatively correlated with DTS, CES and TLEQ scores. Results: We found an interaction between CD-RISC and CES in predicting PTSD severity (Davidson Trauma Scale). Specifically, high resilience predicted lower PTSD symptom severity than low resilience, this relationship was amplified with increasing levels of combat exposure. Structural equation modelling (SEM) identified an optimal latent variable that represents resilience and relationships between latent variables for resilience, trauma, and illness. We derived a resilience latent variable composed of age, education level, MOSSS and race. Conclusions: Our results support a conceptualization of resilience as a multifactorial determinant that coexists with PTSD, a state rather than trait variable, and can be quantified by biological and behavioural metrics. HIGHLIGHTS: • Historically, resilience has often been conceptualized as the sustained lack of symptoms following trauma exposure.• We examined the VA Mid-Atlantic Post Deployment Mental Health Repository (PDMH) comprised of 3876 US Military Veterans.• We found an interaction effect between CD-RISC and CES in predicting PTSD severity (Davidson Trauma Scale).

Antecedentes: Históricamente, la resiliencia a menudo se ha conceptualizado como la ausencia sostenida de síntomas después de la exposición al trauma. En línea con una novedosa conceptualización de la resiliencia como un fenómeno dinámico a lo largo de la vida, determinada por la interacción de factores biológicos y ambientales, examinamos el Repositorio de salud mental post-despliegue VA Mid-Atlantic (PDMH por sus siglas en ingles) compuesto por 3.876 veteranos militares de EE.UU. con y sin diagnósticos de TEPT.Métodos: Realizamos modelos de regresión para estudiar la relación entre resiliencia (medida con la Escala de resiliencia de Connor Davidson; CD-RISC por sus siglas en ingles), gravedad del trastorno de estrés postraumático (TEPT) (con Escala de Trauma de Davidson; DTS por sus siglas en ingles), apoyo social (Encuesta de Estudio de Resultados Médicos - Apoyo Social; MOSSS por sus siglas en ingles), exposición al combate (Escala de exposición al combate; CES por sus siglas en ingles), trauma infantil (Cuestionario de Eventos de vida traumáticos; TLEQ por sus siglas en ingles), y factores demográficos. CD-RISC se correlacionó positivamente con años de educación y se correlacionó negativamente con los puntajes de DTS, CES y TLEQ.Resultados: Encontramos una interacción entre CD-RISC y CES en la predicción de la gravedad del TEPT (Escala de trauma de Davidson). Específicamente, una alta resiliencia predijo menor gravedad de los síntomas de TEPT que una baja resiliencia, esta relación fue amplificada con niveles crecientes de exposición al combate. El modelo de ecuaciones estructurales (SEM por sus siglas en ingles) identificó una variable latente óptima que representa la resiliencia y las relaciones entre las variables latentes de resiliencia, trauma y enfermedad. Derivamos una variable latente de resiliencia compuesta por edad, nivel educativo, MOSSS y raza.Conclusiones: Nuestros resultados apoyan una conceptualización de la resiliencia como un determinante multifactorial que coexiste con el TEPT, una variable de estado más que de rasgo, y puede ser cuantificada con mediciones biológicas y conductuales.

Scan-rescan reliability of subcortical brain volumes derived from automated segmentation.

Large-scale longitudinal studies of regional brain volume require reliable quantification using automated segmentation and labeling. However, repeated MR scanning of the same subject, even if using the same scanner and acquisition parameters, does not result in identical images due to small changes in image orientation, changes in prescan parameters, and magnetic field instability. These differences may lead to appreciable changes in estimates of volume for different structures. This study examined scan-rescan reliability of automated segmentation algorithms for measuring several subcortical regions, using both within-day and across-day comparison sessions in a group of 23 normal participants. We found that the reliability of volume measures including percent volume difference, percent volume overlap (Dice's coefficient), and intraclass correlation coefficient (ICC), varied substantially across brain regions. Low reliability was observed in some structures such as the amygdala (ICC = 0.6), with higher reliability (ICC = 0.9) for other structures such as the thalamus and caudate. Patterns of reliability across regions were similar for automated segmentation with FSL/FIRST and FreeSurfer (longitudinal stream). Reliability was associated with the volume of the structure, the ratio of volume to surface area for the structure, the magnitude of the interscan interval, and the method of segmentation. Sample size estimates for detecting changes in brain volume for a range of likely effect sizes also differed by region. Thus, longitudinal research requires a careful analysis of sample size and choice of segmentation method combined with a consideration of the brain structure(s) of interest and the magnitude of the anticipated effects.

Phase II Study of Immunotherapy With Tecemotide and Bevacizumab After Chemoradiation in Patients With Unresectable Stage III Non-Squamous Non-Small-Cell Lung Cancer (NS-NSCLC): A Trial of the ECOG-ACRIN Cancer Research Group (E6508).

INTRODUCTION: Although chemoradiotherapy (CRT) is the standard of care for patients with unresectable stage III non-small-cell lung cancer (LA-NSCLC), most patients relapse. Tecemotide is a MUC1 antigen-specific cancer immunotherapy vaccine. Bevacizumab improves survival in advanced nonsquamous (NS)-NSCLC and has a role in immune modulation. This phase II trial tested the combination of tecemotide and bevacizumab following CRT in patients with LA-NSCLC. PATIENTS AND METHODS: Subjects with stage III NS-NSCLC suitable for CRT received carboplatin/paclitaxel weekly + 66 Gy followed by 2 cycles of consolidation carboplatin/paclitaxel ≤ 4 weeks of completion of CRT (Step 1). Patients with partial response/stable disease after consolidation therapy were registered onto step 2, which was 6 weekly tecemotide injections followed by every 6 weekly injections and bevacizumab every 3 weeks for up to 34 doses. The primary endpoint was to determine the safety of this regimen. RESULTS: Seventy patients were enrolled; 68 patients (median age, 63 years; 56% male; 57% stage IIIA) initiated therapy, but only 39 patients completed CRT and consolidation therapy per protocol, primarily owing to disease progression or toxicity. Thirty-three patients (median age, 61 years; 58% male; 61% stage IIIA) were registered to step 2 (tecemotide + bevacizumab). The median number of step 2 cycles received was 11 (range, 2-25). Step 2 worst toxicity included grade 3, N = 9; grade 4, N = 1; and grade 5, N = 1. Grade 5 toxicity in step 2 was esophageal perforation attributed to bevacizumab. Among the treated and eligible patients (n = 32) who were treated on step 2, the median overall survival was 42.7 months (95% confidence interval, 21.7-63.3 months), and the median progression-free survival was 14.9 months (95% confidence interval, 11.0-20.9 months) from step 1 registration. CONCLUSIONS: This cooperative group trial met its endpoint, demonstrating tolerability of bevacizumab + tecemotide after CRT and consolidation. In this selected group of patients, the median progression-free survival and overall survival are encouraging. Given that consolidation immunotherapy is now a standard of care following CRT in patients with LA-NSCLC, these results support a role for continued investigation of antiangiogenic and immunotherapy combinations in LA-NSCLC.

Advanced oral tongue cancer in a 22-year-old pregnant woman.

OBJECTIVES: Oral squamous cell carcinoma generally occurs in older men and is associated mostly with tobacco and alcohol as the primary risk factors. The incidence of oral squamous cell carcinoma in younger patients has increased. We report a case of a young woman, 25 weeks pregnant, who presented with stage IV carcinoma of the oral tongue. METHODS: The following is a case presentation and literature review. RESULTS: The patient presented with T4 N3 M0 oral tongue cancer. A team consisting of a head and neck surgeon, a radiation oncologist, a medical oncologist, and a maternal-fetal medicine specialist was assembled. The patient initially refused surgery. Chemotherapy was initiated until 32 weeks' gestation. After an infant boy was delivered via cesarean section, the patient began concurrent irradiation and chemotherapy, which induced complete regression of the primary tongue neoplasm with a partial response of the neck nodes. The patient underwent bilateral neck dissection followed by hemiglossectomy for recurrence. CONCLUSIONS: Management of advanced oral carcinoma in pregnancy presents a unique set of challenges. Few studies have described chemotherapy and radiotherapy during pregnancy, and long-term results are needed. Care must be taken to balance appropriate and adequate treatment of disease and to ensure the safety of the patient and the fetus.

Widespread Cortical Thickness Is Associated With Neuroactive Steroid Levels.

BACKGROUND: Neuroactive steroids are endogenous molecules with regenerative and neuroprotective actions. Both cortical thickness and many neuroactive steroid levels decline with age and are decreased in several neuropsychiatric disorders. However, a systematic examination of the relationship between serum neuroactive steroid levels and in vivo measures of cortical thickness in humans is lacking. METHODS: Peripheral serum levels of seven neuroactive steroids were assayed in United States military veterans. All (n = 143) subsequently underwent high-resolution structural MRI, followed by parcellelation of the cortical surface into 148 anatomically defined regions. Regression modeling was applied to test the association between neuroactive steroid levels and hemispheric total gray matter volume as well as region-specific cortical thickness. False discovery rate (FDR) correction was used to control for Type 1 error from multiple testing. RESULTS: Neuroactive steroid levels of allopregnanolone and pregnenolone were positively correlated with gray matter thickness in multiple regions of cingulate, parietal, and occipital association cortices (r = 0.20-0.47; p < 0.05; FDR-corrected). CONCLUSION: Positive associations between serum neuroactive steroid levels and gray matter cortical thickness are found in multiple brain regions. If these results are confirmed, neuroactive steroid levels and cortical thickness may help in monitoring the clinical response in future intervention studies of neuroregenerative therapies.

Implementation of fiducial-based image registration in the Cyberknife robotic system.

Fiducial-based image registration methodology as implemented in the Cyberknife system is explored. The Cyberknife is a radiosurgery system that uses image guidance technology and computer-controlled robotics to determine target positions and adjust beam directions accordingly during the dose delivery. The image guidance system consists of 2 x-ray sources mounted on the ceiling and a detection system mounted on both sides of the treatment couch. Two orthogonal live radiographs are taken prior to and during patient treatment. Fiducial markers are identified on these radiographs and compared to a library of digital reconstructed radiographs (DRRs) using the fiducial extraction software. The fiducial extraction software initially sets an intensity threshold on the live radiographs to generate white areas on black images referred to as "blobs." Different threshold values are being used and blobs at the same location are assumed to originate from the same object. The number of blobs is then reduced by examining each blob against a predefined set of properties such as shape and exposure levels. The remaining blobs are further reduced by examining the location of the blobs in the inferior-superior patient axis. Those blobs that have the corresponding positions are assumed to originate from the same object. The remaining blobs are used to create fiducial configurations and are compared to the reference configuration from the computed tomography (CT) image dataset for treatment planning. The best-fit configuration is considered to have the appropriate fiducial markers. The patient position is determined based on these fiducial markers. During the treatment, the radiation beam is turned off when the Cyberknife changes nodes. This allows a time window to acquire live radiographs for the determination of the patient target position and to update the robotic manipulator to change beam orientations accordingly.

Multimodality image fusion and planning and dose delivery for radiation therapy.

Image-guided radiation therapy (IGRT) relies on the quality of fused images to yield accurate and reproducible patient setup prior to dose delivery. The registration of 2 image datasets can be characterized as hardware-based or software-based image fusion. Hardware-based image fusion is performed by hybrid scanners that combine 2 distinct medical imaging modalities such as positron emission tomography (PET) and computed tomography (CT) into a single device. In hybrid scanners, the patient maintains the same position during both studies making the fusion of image data sets simple. However, it cannot perform temporal image registration where image datasets are acquired at different times. On the other hand, software-based image fusion technique can merge image datasets taken at different times or with different medical imaging modalities. Software-based image fusion can be performed either manually, using landmarks, or automatically. In the automatic image fusion method, the best fit is evaluated using mutual information coefficient. Manual image fusion is typically performed at dose planning and for patient setup prior to dose delivery for IGRT. The fusion of orthogonal live radiographic images taken prior to dose delivery to digitally reconstructed radiographs will be presented. Although manual image fusion has been routinely used, the use of fiducial markers has shortened the fusion time. Automated image fusion should be possible for IGRT because the image datasets are derived basically from the same imaging modality, resulting in further shortening the fusion time. The advantages and limitations of both hardware-based and software-based image fusion methodologies are discussed.

Clofarabine followed by haploidentical stem cell transplant using fludarabine, busulfan, and total-body irradiation with post-transplant cyclophosphamide in non-remission AML.

Approximately 30-40% of patients with acute myeloid leukemia (AML) experience induction failures. In these patients who do not achieve remission with two cycles of standard induction therapies, the probability of achieving remission with subsequent inductions is very limited. Hematopoietic stem cell transplantation (HSCT) is the only curative option for these patients, but high relapse rate and transplant-related mortality often preclude them to proceed to transplant. Thus, AML not in remission at time of HSCT remains a huge unmet need in current HSCT practice, particularly if the patient does not have an HLA-matched donor identified by the time of two induction failures. We used clofarabine cytoreduction immediately followed by fludarabine (Flu) and busulfan (Bu) × 3 with total-body irradiation (TBI) conditioning (Flu/Bu3/TBI) for haploidentical peripheral blood stem cell transplant with post-transplant cyclophosphamide for two cases of refractory AML with a very high tumor burden at transplant and achieved complete remission by day + 30 in both cases.

Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition).

STUDY OBJECTIVES: Stage IIIA non-small cell lung cancer represents a relatively heterogeneous group of patients with metastatic disease to the ipsilateral mediastinal (N2) lymph nodes and also includes T3N1 patients. Presentations of disease range from apparently resectable tumors with occult microscopic nodal metastases to unresectable, bulky multistation nodal disease. This review explores the published clinical trials to make treatment recommendations in this controversial subset of lung cancer. DESIGN, SETTING, AND PARTICIPANTS: Systematic searches were made of MEDLINE, HealthStar, and Cochrane Library databases up to May 2006, focusing primarily on randomized trials, with inclusion of selected metaanalyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables. MEASUREMENT AND RESULTS: The evidence derived from the literature now appears to support routine adjuvant chemotherapy after complete resection of stage IIIA lung cancer encountered unexpectedly at surgery. However, using neoadjuvant therapy followed by surgery for known stage IIIA lung cancer as a routine therapeutic option is not supported by current published randomized trials. Combination chemoradiotherapy, especially delivered concurrently, is still the preferred treatment for prospectively recognized stage IIIA lung cancer with all degrees of mediastinal lymph node involvement. Current and future trials may modify these recommendations. CONCLUSIONS: Multimodality therapy of some type appears to be preferable in all subsets of stage IIIA patients. However, because of the relative lack of consistent randomized trial data in this subset, the following evidence-based treatment guidelines lack compelling evidence in most scenarios.

Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone.

There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.