Juxtametallic Bipolar Bone Radiofrequency Ablation: Thermal Monitoring in an Ex-Vivo Model with Specimen MRI and Histopathologic Correlation.

PURPOSE: To measure the ablation zone temperature and nontarget tissue temperature during radiofrequency (RF) ablation in bone containing metal instrumentation versus no metal instrumentation (control group). MATERIALS AND METHODS: Ex vivo experiments were performed on 15 swine vertebrae (control, n = 5; titanium screw, n = 5; stainless steel screw, n = 5). Screws and RF ablation probe were inserted identically under fluoroscopy. During RF ablation (3 W, 5 minutes), temperature was measured 10 mm from RF ablation centerpoint and in muscle contacting the screw. Magnetic resonance (MR) imaging, gross pathologic, and histopathologic analyses were performed on 1 specimen from each group. RESULTS: Ablation zone temperatures at 2.5 and 5 minutes increased by 12.2 °C ± 2.6 °C and 21.5 °C ± 2.1 °C (control); 11.0 °C ± 4.1 °C and 20.0 °C ± 2.9 °C (juxta-titanium screw), and 10.0 °C ± 3.4 °C and 17.2 °C ± 3.5 °C (juxta-stainless steel) screw; differences among groups did not reach significance by analysis of variance (P = .87). Mixed-effects linear regression revealed a statistically significant increase in temperature over time in all 3 groups (4.2 °C/min ± 0.4 °C/min, P < .001). Compared with the control, there was no significant difference in the temperature change over time for titanium (-0.3 °C/min ± 0.5 °C/min, P = .53) or steel groups (-0.4 °C/min ± 0.5 °C/min, P = .38). The mean screw temperature at the final time point did not show a statistically significant change compared with baseline in either the titanium group (-1.2 °C ± 2.3 °C, P = .50) or steel group (2.6 °C ± 2.9 °C, P = .11). MR imaging and pathologic analyses revealed homogeneous ablation without sparing of the peri-hardware zones. CONCLUSIONS: Adjacent metallic instrumentation did not affect the rate of or absolute increase in temperature in the ablation zone, did not create peri-metallic ablation inhomogeneities, and did not result in significant nontarget heating of muscle tissue in contact with the metal instrumentation.

Divergent Interpretations of Imaging After Stereotactic Body Radiation Therapy for Lung Cancer.

PURPOSE: Conflicting information from health care providers contributes to anxiety among cancer patients. The purpose of this study was to investigate discordant interpretations of follow-up imaging studies after lung stereotactic body radiation therapy (SBRT) between radiologists and radiation oncologists. METHODS AND MATERIALS: Patients treated with SBRT for stage I non-small cell lung cancer from 2007 to 2018 at Duke University Medical Center were included. Radiology interpretations of follow-up computed tomography (CT) chest or positron emission tomography (PET)/CT scans and the corresponding radiation oncology interpretations in follow-up notes from the medical record were assessed. Based on language used, interpretations were scored as concerning for progression (Progression), neutral differential listed (Neutral Differential), or favor stability/postradiation changes (Stable). Neutral Differential required that malignancy was specifically listed as a possibility in the differential. Encounters were categorized as discordant when either radiology or radiation oncology interpreted the surveillance imaging as Progression when the other interpreted the imaging study as Stable or Neutral Differential. The incidence of discordant interpretations was the primary endpoint of the study. RESULTS: From 2007 to 2018, 139 patients were treated with SBRT and had available follow-up CT or PET-CT imaging for the analysis. Median follow-up was 61 months and the median number of follow-up encounters per patient was 3. Of 534 encounters evaluated, 25 (4.7%) had overtly discordant interpretations of imaging studies. This most commonly arose when radiology felt the imaging study showed Progression but radiation oncology favored Stable or Neutral Differential (24/25, 96%). No patient or treatment variables were found to be significantly associated with discordant interpretations on univariate analysis including type of scan (CT 22/489, 4.5%; PET-CT 3/45, 7%; P = .46). CONCLUSIONS: Surveillance imaging after lung SBRT is often interpreted differently by radiologists and radiation oncologists, but overt discordance was relatively low at our institution. Providers should be aware of differences in interpretation patterns that may contribute to increased patient distress.

Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With or Without Radiation Therapy: A 25-Year Retrospective Analysis of a Single-Institution Experience.

Purpose: Atypical (World Health Organization [WHO] grade 2) and malignant (WHO grade 3) meningiomas have high rates of local recurrence, and questions remain about the role of adjuvant radiation therapy (RT) for patients with WHO grade 2 disease. These patients frequently require salvage therapy, and optimal management is uncertain given limited prospective data. We report on the long-term outcomes for patients with atypical and malignant meningiomas treated with surgery and/or RT at our institution. Methods and Materials: Data were collected through a retrospective chart review for all patients with WHO grade 2 or 3 meningiomas treated with surgery and/or RT at our institution between January 1992 and March 2017. Progression-free survival (PFS) and overall survival (OS) were described using the KaplanMeier estimator. The outcomes in the subgroups were compared with a log-rank test. A Cox proportional hazards model was used for the univariable and multivariable analyses of predictors of PFS. Results: A total of 66 patients were included in this analysis. The median follow-up was 12.4 years overall and 8.6 years among surviving patients. Fifty-two patients (78.8%) had WHO grade 2 meningiomas, and 14 patients (21.2%) had WHO grade 3 disease. Thirty-six patients (54.5%) were treated with surgery alone, 28 patients (42.4%) with surgery and adjuvant RT, and 2 patients (3%) with RT alone. Median PFS and OS were 3.2 years and 8.8 years, respectively. PFS was significantly improved with adjuvant RT compared with surgery alone (hazard ratio, 0.36; 95% confidence interval, 0.18-0.70). Patients with Ki-67 index >10% showed a trend toward worse PFS compared with patients with Ki-67 ≤10% (hazard ratio, 0.51; 95% confidence interval, 0.25-1.04). No significant differences in PFS or OS were observed with respect to Simpson or WHO grade. Conclusions: For patients with atypical or malignant meningiomas, adjuvant RT was associated with significantly improved PFS, and Ki-67 index >10% was associated with a trend toward worse PFS. Given the long-term survival, high recurrence rates, and efficacy of salvage therapy, patients with atypical and malignant meningiomas should be monitored systematically long after initial treatment.

Estrogen/progesterone receptor and HER2 discordance between primary tumor and brain metastases in breast cancer and its effect on treatment and survival.

BACKGROUND: Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM). METHODS: A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the BCBM. RESULTS: The overall receptor discordance rate was 132/316 (42%), and the subtype discordance rate was 100/316 (32%). Hormone receptors (HR, either ER or PR) were gained in 40/160 (25%) patients with HR-negative primary tumors. HER2 was gained in 22/173 (13%) patients with HER2-negative primary tumors. Subsequent treatment was not adjusted for most patients who gained receptors-nonetheless, median survival (MS) improved but did not reach statistical significance (HR, 17-28 mo, P = 0.12; HER2, 15-19 mo, P = 0.39). MS for patients who lost receptors was worse (HR, 27-18 mo, P = 0.02; HER2, 30-18 mo, P = 0.08). CONCLUSIONS: Receptor discordance between primary tumor and BCBM is common, adversely affects survival if receptors are lost, and represents a missed opportunity for use of effective treatments if receptors are gained. Receptor analysis of BCBM is indicated when clinically appropriate. Treatment should be adjusted accordingly. KEY POINTS: 1. Receptor discordance alters subtype in 32% of BCBM patients.2. The frequency of receptor gain for HR and HER2 was 25% and 13%, respectively.3. If receptors are lost, survival suffers. If receptors are gained, consider targeted treatment.

Beyond an Updated Graded Prognostic Assessment (Breast GPA): A Prognostic Index and Trends in Treatment and Survival in Breast Cancer Brain Metastases From 1985 to Today.

PURPOSE: Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts. METHODS AND MATERIALS: A multi-institutional (19), multinational (3), retrospective database of 2473 patients with breast cancer with newly diagnosed brain metastases (BCBM) diagnosed from January 1, 2006, to December 31, 2017, was created and compared with prior cohorts. Associations of PF and treatment with survival were analyzed. Kaplan-Meier survival estimates were compared with log-rank tests. PF were weighted and the Breast GPA was updated such that a GPA of 0 and 4.0 correlate with the worst and best prognoses, respectively. RESULTS: Median survival (MS) for cohorts A, B, and C improved over time (from 11, to 14 to 16 months, respectively; P < .01), despite the subtype distribution becoming less favorable. PF significant for survival were tumor subtype, Karnofsky Performance Status, age, number of BCBMs, and extracranial metastases (all P < .01). MS for GPA 0 to 1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 was 6, 13, 24, and 36 months, respectively. Between cohorts B and C, the proportion of human epidermal receptor 2 + subtype decreased from 31% to 18% (P < .01) and MS in this subtype increased from 18 to 25 months (P < .01). CONCLUSIONS: MS has improved modestly but varies widely by diagnosis-specific PF. New PF are identified and incorporated into an updated Breast GPA (free online calculator available at brainmetgpa.com). The Breast GPA facilitates clinical decision-making and will be useful for stratification of future clinical trials. Furthermore, these data suggest human epidermal receptor 2-targeted therapies improve clinical outcomes in some patients with BCBM.

Survival in Patients With Brain Metastases: Summary Report on the Updated Diagnosis-Specific Graded Prognostic Assessment and Definition of the Eligibility Quotient.

PURPOSE: Conventional wisdom has rendered patients with brain metastases ineligible for clinical trials for fear that poor survival could mask the benefit of otherwise promising treatments. Our group previously published the diagnosis-specific Graded Prognostic Assessment (GPA). Updates with larger contemporary cohorts using molecular markers and newly identified prognostic factors have been published. The purposes of this work are to present all the updated indices in a single report to guide treatment choice, stratify research, and define an eligibility quotient to expand eligibility. METHODS: A multi-institutional database of 6,984 patients with newly diagnosed brain metastases underwent multivariable analyses of prognostic factors and treatments associated with survival for each primary site. Significant factors were used to define the updated GPA. GPAs of 4.0 and 0.0 correlate with the best and worst prognoses, respectively. RESULTS: Significant prognostic factors varied by diagnosis and new prognostic factors were identified. Those factors were incorporated into the updated GPA with robust separation (P < .01) between subgroups. Survival has improved, but varies widely by GPA for patients with non-small-cell lung, breast, melanoma, GI, and renal cancer with brain metastases from 7-47 months, 3-36 months, 5-34 months, 3-17 months, and 4-35 months, respectively. CONCLUSION: Median survival varies widely and our ability to estimate survival for patients with brain metastases has improved. The updated GPA (available free at brainmetgpa.com) provides an accurate tool with which to estimate survival, individualize treatment, and stratify clinical trials. Instead of excluding patients with brain metastases, enrollment should be encouraged and those trials should be stratified by the GPA to ensure those trials make appropriate comparisons. Furthermore, we recommend the expansion of eligibility to allow for the enrollment of patients with previously treated brain metastases who have a 50% or greater probability of an additional year of survival (eligibility quotient > 0.50).

Chemotherapy-Induced Tunneling Nanotubes Mediate Intercellular Drug Efflux in Pancreatic Cancer.

Intercellular communication plays a critical role in the ever-evolving landscape of invasive cancers. Recent studies have elucidated the potential role of tunneling nanotubes (TNTs) in this function. TNTs are long, filamentous, actin-based cell protrusions that mediate direct cell-to-cell communication between malignant cells. In this study, we investigated the formation of TNTs in response to variable concentrations of the chemotherapeutic drug doxorubicin, which is used extensively in the treatment of cancer patients. Doxorubicin stimulated an increased formation of TNTs in pancreatic cancer cells, and this occurred in a dose-dependent fashion. Furthermore, TNTs facilitated the intercellular redistribution of this drug between connected cells in both pancreatic and ovarian cancer systems in vitro. To provide supportive evidence for the relevance of TNTs in pancreatic cancer in vivo, we performed multiphoton fluorescence microscopy and imaged TNTs in tumor specimens resected from three human patients with pancreatic adenocarcinoma, and one with neuroendocrine carcinoma. In sum, TNT formation was upregulated in aggressive forms of pancreatic carcinoma, was further stimulated after chemotherapy exposure, and acted as a novel method for drug efflux. These findings implicate TNTs as a potential novel mechanism of drug resistance in chemorefractory forms of cancer.

Effect of Targeted Therapies on Prognostic Factors, Patterns of Care, and Survival in Patients With Renal Cell Carcinoma and Brain Metastases.

PURPOSE: To identify prognostic factors, define evolving patterns of care, and the effect of targeted therapies in a larger contemporary cohort of renal cell carcinoma (RCC) patients with new brain metastases (BM). METHODS AND MATERIALS: A multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new BM diagnosed from January 1, 2006, to December 31, 2015, was created. Clinical parameters and treatment were correlated with median survival and time from primary diagnosis to BM. Multivariable analyses were performed. RESULTS: The median survival for the prior/present cohorts was 9.6/12 months, respectively (P < .01). Four prognostic factors (Karnofsky performance status, extracranial metastases, number of BM, and hemoglobin b) were significant for survival after the diagnosis of BM. Of the 6 drug types studied, only cytokine use after BM was associated with improved survival. The use of whole-brain radiation therapy declined from 50% to 22%, and the use of stereotactic radiosurgery alone increased from 46% to 58%. Nonneurologic causes of death were twice as common as neurologic causes. CONCLUSIONS: Additional prognostic factors refine prognostication in this larger contemporary cohort. Patterns of care have changed, and survival of RCC patients with BM has improved over time. The reasons for this improvement in survival remain unknown but may relate to more aggressive use of local brain metastasis therapy and a wider array of systemic treatment options for those patients with progressive extracranial tumor.

Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool.

Background: Brain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published the Renal Graded Prognostic Assessment (GPA) tool. In our prior RCC study (n = 286, 1985-2005), we found marked heterogeneity and variation in outcomes. In our recent update in a larger, more contemporary cohort, we identified additional significant prognostic factors. The purpose of this study is to update the original Renal-GPA based on the newly identified prognostic factors. Methods: A multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new brain metastases diagnosed from January 1, 2006 to December 31, 2015 was created. Clinical parameters and treatment were correlated with survival. A revised Renal GPA index was designed by weighting the most significant factors in proportion to their hazard ratios and assigning scores such that the patients with the best and worst prognoses would have a GPA of 4.0 and 0.0, respectively. Results: The 4 most significant factors were Karnofsky performance status, number of brain metastases, extracranial metastases, and hemoglobin. The overall median survival was 12 months. Median survival for GPA groups 0-1.0, 1.5-2.0, 2.5-3, and 3.5-4.0 (% n = 25, 27, 30 and 17) was 4, 12, 17, and 35 months, respectively. Conclusion: The updated Renal GPA is a user-friendly tool that will help clinicians and patients better understand prognosis, individualize clinical decision making and treatment selection, provide a means to compare retrospective literature, and provide more robust stratification of future clinical trials in this heterogeneous population. To simplify use of this tool in daily practice, a free online application is available at brainmetgpa.com.

Case Report of Extended Survival and Quality of Life in a Melanoma Patient with Multiple Brain Metastases and Review of Literature.

Long-term survival for melanoma patients with multiple brain metastases is rare. A review of the literature reveals only three reported melanoma patients with multiple brain metastases who survived more than 10 years. We present a patient who is recurrence-free 11 years after the diagnosis of three brain metastases. Her treatment consisted of cytokine (interferon and interleukin-2) and chemotherapy nine months prior to developing brain and soft tissue metastases, which were treated with stereotactic radiosurgery and stereotactic ablative radiotherapy, respectively, followed by six months of chemotherapy. Notably, she has not received any treatment for over 10 years, never underwent craniotomy or whole brain radiation therapy, currently has a perfect score on the functional assessment of cancer therapy for brain (FACT-Br) quality of life (QoL) scale, and runs marathons. This treatment course is consistent with emerging literature on the abscopal effect (radiation-induced immune response). Clinical trials are needed to better understand and harness the abscopal effect in order to optimally integrate targeted drug and radiation therapies.

Early Initiation of Breastfeeding Among Maya Mothers in the Western Highlands of Guatemala: Practices and Beliefs.

BACKGROUND: Guatemala exhibits the sixth highest rate of child stunting worldwide, and stunting disproportionately affects Guatemala indigenous communities. In a country struggling to combat this result of malnutrition, early child nutrition is especially critical. Specifically, early initiation of breastfeeding is important for the development of newborn infants. Understanding beliefs and practices related to early initiation of breastfeeding in Maya Guatemala may provide an avenue to guide nutrition interventions in indigenous communities. Research aim: This study aimed to determine major beliefs and practices associated with early initiation of breastfeeding among Maya mothers in Lake Atitlán, Guatemala. METHODS: As part of a larger study to assess child nutrition in the Lake Atitlán region, we created a series of semistructured interview questions to document breastfeeding practices and beliefs among mothers. We conducted and audio-recorded in-person interviews that were translated from Kaqchikel, the local language, to Spanish by a community assistant. RESULTS: We conducted 178 interviews with mothers; 76% practiced early initiation. Early initiation was associated with the village and complementary feeding practices. Mothers held a variety of beliefs about the value of colostrum, and these beliefs were associated with the village. Mothers who held negative beliefs toward colostrum were more likely to delay breastfeeding initiation. CONCLUSION: Although most Maya mothers practice early initiation, the intervillage disparity in breastfeeding practices demonstrates a need to geographically focus breastfeeding interventions. Our novel insights into the breastfeeding beliefs among Maya mothers will serve as a guide to structure culturally competent breastfeeding education interventions in indigenous communities.

The Prognostic Value of BRAF, C-KIT, and NRAS Mutations in Melanoma Patients With Brain Metastases.

PURPOSE: Brain metastases are a common problem in patients with melanoma, but little is known about the effect of gene mutations on survival in these patients. METHODS AND MATERIALS: We created a retrospective multi-institutional database of 823 patients with melanoma and brain metastases diagnosed between 2006 and 2015. Clinical parameters, gene mutation status (BRAF, C-KIT, NRAS), and treatment were correlated with survival. Treatment patterns and outcomes were compared with a prior era (1985-2005). RESULTS: BRAF status was known in 584 of 823 patients (71%). BRAF, NRAS, and C-KIT mutations were present in 51%, 22%, and 11% of tested patients, respectively. The median time from primary diagnosis to brain metastasis was 32 months, and overall median survival (MS) from the time of initial treatment of brain metastases was 10 months. MS for BRAF-positive and BRAF-negative patients was 13 months and 9 months, respectively (P=.02). There was no significant difference in MS in patients with or without NRAS or C-KIT mutations. The time from primary diagnosis to brain metastasis did not vary by mutation and was not associated with survival after the diagnosis of brain metastases. MS for the 1985 to 2005 and 2006 to 2015 cohorts was 6.7 months and 10.0 months, respectively (P<.01). Reflecting treatment-trend changes, use of whole-brain radiation therapy decreased from 48% to 26% during this period. Among BRAF-positive patients, 71% received targeted BRAF and/or MEK inhibitors and 57% received some combination of targeted therapy, chemotherapy, and/or immunotherapy. CONCLUSIONS: For melanoma patients with brain metastases, BRAF-positive patients survive longer than BRAF-negative patients and overall survival has improved from 1985-2005 to 2006-2015.

Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA).

IMPORTANCE: Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. As systemic therapies improve, patients with lung cancer live longer and thus are at increased risk for brain metastases. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials. OBJECTIVE: To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with non-small-cell lung cancer (NSCLC) and brain metastases. The DS-GPA is based on data from patients diagnosed between 1985 and 2005, and we set out to update it by incorporating more recently reported gene and molecular alteration data for patients with NSCLC and brain metastases. This new index is called the Lung-molGPA. DESIGN, SETTING, AND PARTICIPANTS: This is a multi-institutional retrospective database analysis of 2186 patients diagnosed between 2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable analyses took place between December 2015 and May 2016, and all prognostic factors were weighted for significance by hazard ratios. Significant factors were included in the updated Lung-molGPA prognostic index. MAIN OUTCOMES AND MEASURES: The main outcome was survival. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. Log rank tests were used to compare adjacent classes and to compare overall survival for adenocarcinoma vs nonadenocarcinoma groups. RESULTS: The original DS-GPA was based on 4 factors found in 1833 patients with NSCLC and brain metastases diagnosed between 1985 and 2005: patient age, Karnofsky Performance Status, extracranial metastases, and number of brain metastases. The patients studied for the creation of the DS-GPA had a median survival of 7 months from the time of initial treatment of brain metastases. To design the updated Lung-molGPA, we analyzed data from 2186 patients from 2006 through 2014 with NSCLC and newly diagnosed brain metastases (1521 adenocarcinoma and 665 nonadenocarcinoma). Significant prognostic factors included the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations in patients with adenocarcinoma (mutation status was not routinely tested for nonadenocarcinoma). The overall median survival for the cohort in the present study was 12 months, and those with NSCLC-adenocarcinoma and Lung-molGPA scores of 3.5 to 4.0 had a median survival of nearly 4 years. CONCLUSIONS AND RELEVANCE: In recent years, patient survival and physicians' ability to predict survival in NSCLC with brain metastases has improved significantly. The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical decision making and appropriate stratification of future clinical trials.

Estimating Survival in Melanoma Patients With Brain Metastases: An Update of the Graded Prognostic Assessment for Melanoma Using Molecular Markers (Melanoma-molGPA).

PURPOSE: To update the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for a markedly heterogeneous patient population, patients with melanoma and brain metastases, using a larger, more current cohort, including molecular markers. METHODS: The original Melanoma-GPA is based on data from 483 patients whose conditions were diagnosed between 1985 and 2005. This is a multi-institutional retrospective database analysis of 823 melanoma patients with newly diagnosed brain metastases from January 1, 2006, to December 31, 2015. Multivariable analyses identified significant prognostic factors, which were weighted and included in the updated index (Melanoma-molGPA). Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios to design the updated Melanoma-molGPA in which scores of 4.0 and 0.0 are associated with the best and worst prognoses, as with all of the diagnosis-specific GPA indices. Log-rank tests were used to compare adjacent classes. RESULTS: There were 5 significant prognostic factors for survival (age, Karnofsky performance status [KPS], extracranial metastases [ECM], number of brain metastases, and BRAF status), whereas only KPS and the number of brain metastases were significant in the original Melanoma-GPA. Median survival improved from 6.7 to 9.8 months between the 2 treatment eras, and the median survival times for patients with Melanoma-molGPA of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 4.9, 8.3, 15.8, and 34.1 months (P<.0001 between each adjacent group). CONCLUSIONS: Survival and our ability to estimate survival in melanoma patients with brain metastases has improved significantly. The updated Melanoma-molGPA, a user-friendly tool to estimate survival, will facilitate clinical decision making regarding whether and which treatment is appropriate and will also be useful for stratification of future clinical trials. To further simplify use, a free online/smart phone app is available at brainmetgpa.com.

The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases.

PURPOSE: Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno). METHODS: A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials. RESULTS: Of 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR-/+ was 10/15 months (P=.02) and for ALK-/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK-, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-naïve patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P=.84]/1.60 [P=.45], respectively). The CoD was nonneurologic in 82% of patients with known CoD. CONCLUSION: EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.