Survival and outcomes in patients with ≥ 25 cumulative brain metastases treated with stereotactic radiosurgery.

OBJECTIVE: In the era in which more patients with greater numbers of brain metastases (BMs) are being treated with stereotactic radiosurgery (SRS) alone, it is critical to understand how patient, tumor, and treatment factors affect functional status and overall survival (OS). The authors examined the survival outcomes and dosimetry to critical structures in patients treated with Gamma Knife radiosurgery (GKRS) for ≥ 25 metastases in a single session or cumulatively over the course of their disease. METHODS: A retrospective analysis was conducted at a single institution. The institution's prospective Gamma Knife (GK) SRS registry was queried to identify patients treated with GKRS for ≥ 25 cumulative BMs between June 2013 and April 2020. Ninety-five patients were identified, and their data were used for analysis. Treatment plans for dosimetric analysis were available for 89 patients. Patient, tumor, and treatment characteristics were identified, and outcomes and OS were evaluated. RESULTS: The authors identified 1132 patients with BMs in their institutional registry. Ninety-five patients were treated for ≥ 25 cumulative metastases, resulting in a total of 3596 tumors treated during 373 separate treatment sessions. The median number of SRS sessions per patient was 3 (range 1-12 SRS sessions), with nearly all patients (n = 93, 98%) having > 1 session. On univariate analysis, factors affecting OS in a statistically significant manner included histology, tumor volume, tumor number, diagnosis-specific graded prognostic assessment (DS-GPA), brain metastasis velocity (BMV), and need for subsequent whole-brain radiation therapy (WBRT). The median of the mean WB dose was 4.07 Gy (range 1.39-10.15 Gy). In the top quartile for both the highest cumulative number and highest cumulative volume of treated metastases, the median of the mean WB dose was 6.14 Gy (range 4.02-10.15 Gy). Seventy-nine patients (83%) had all treated tumors controlled at last follow-up, reflecting the high and durable control rate. Corticosteroids for tumor- or treatment-related effects were prescribed in just over one-quarter of the patients. Of the patients with radiographically proven adverse radiation effects (AREs; 15%), 4 were symptomatic. Four patients required subsequent craniotomy for hemorrhage, progression, or AREs. CONCLUSIONS: In selected patients with a large number of cumulative BMs, multiple courses of SRS are feasible and safe. Together with new systemic therapies, the study results demonstrate that the achieved survival rates compare favorably to those of larger contemporary cohorts, while avoiding WBRT in the majority of patients. Therefore, along with the findings of other series, this study supports SRS as a standard practice in selected patients with larger numbers of BMs.

Hippocampal sparing in patients receiving radiosurgery for ≥25 brain metastases.

PURPOSE/OBJECTIVES: To report our dosimetric analysis of the hippocampi (HC) and the incidence of perihippocampal tumor location in patients with ≥25 brain metastases who received stereotactic radiosurgery (SRS) in single or multiple sessions. MATERIALS/METHODS: Analysis of our prospective registry identified 89 patients treated with SRS for ≥25 brain metastases. HC avoidance regions (HA-region) were created on treatment planning MRIs by 5 mm expansion of HC. Doses from each session were summed to calculate HC dose. The distribution of metastases relative to the HA-region and the HC was analyzed. RESULTS: Median number of tumors irradiated per patient was 33 (range 25-116) in a median of 3 (range1-12) sessions. Median bilateral HC Dmin (D100), D40, D50, Dmax, and Dmean (Gy) was 1.88, 3.94, 3.62, 16.6, and 3.97 for all patients, and 1.43, 2.99, 2.88, 5.64, and 3.07 for patients with tumors outside the HA-region. Multivariate linear regression showed that the median HC D40, D50, and Dmin were significantly correlated with the tumor number and tumor volume (p < 0.001). Of the total 3059 treated tumors, 83 (2.7%) were located in the HA-region in 57% evaluable patients; 38 tumors (1.2%) abutted or involved the HC itself. CONCLUSIONS: Hippocampal dose is higher in patients with tumors in the HA-region; however, even for patients with a high burden of intracranial disease and tumors located in the HA-regions, SRS affords hippocampal sparing. This is particularly relevant in light of our finding of eventual perihippocampal metastases in more than half of our patients.

Patterns of Care and Survival Outcomes in the Treatment of Anal Melanoma.

PURPOSE: Anal mucosal melanoma is an uncommon malignancy of the anal canal, with few large studies available to establish clear trends in the treatment modalities presently available. The primary goal of this study was to identify the patterns of care in the treatment of anal melanoma and secondarily to determine outcomes. METHODS: This was a retrospective study performed utilizing the National Cancer Database (NCDB). A total of 787 patients diagnosed with anal melanoma between 2004 and 2014 were selected, of which 398 had staging information. The four treatment groups analyzed were surgical excision alone, surgical excision and radiation therapy, surgical excision and immunotherapy/chemotherapy, and radiation therapy plus minus immunotherapy/chemotherapy. Treatment was grouped by extent of disease; the Kaplan-Meier method was used to analyze overall survival and multivariate Cox proportional model was used to identify factors associated with overall survival. RESULTS: The majority of patients presented with either node-positive (39.4%) or metastatic disease (37.4%). Patients with surgical excision and radiation therapy had the highest median survival at 32.3 months. This is in contrast with those receiving surgical excision alone (22.9 months), surgery and immunotherapy/chemotherapy (18.4 months), and radiation without surgery (5.1 months) (p < 0.0001). CONCLUSIONS: Treatment with surgical excision was the most common initial treatment with no single modality superior over another in this rare entity.

Patterns of Care and Comparison of Outcomes Between Primary Anal Squamous Cell Carcinoma and Anal Adenocarcinoma.

BACKGROUND: The management of adenocarcinoma of the anus can be challenging because there are few data on outcomes and trends in its treatment to date. OBJECTIVE: This study aimed to compare and analyze the patterns of care and survival outcomes of patients with anal squamous cell carcinoma and anal adenocarcinoma. DESIGN: This was a retrospective study. SETTING: This study was performed by utilizing the National Cancer Database. PATIENTS: We selected a total of 19,539 patients between 2004 and 2014 with stage II to III squamous cell carcinoma or adenocarcinoma of the anus. INTERVENTION: The treatment groups analyzed were surgery alone, neoadjuvant chemoradiation followed by surgery, surgery followed by adjuvant chemoradiation, or definitive chemoradiation. MAIN OUTCOME MEASURES: Patient- and clinical-related factors were compared between the 2 groups. Kaplan-Meier and Cox proportional hazards regression models were used to assess overall survival. RESULTS: Of the patients studied, 18,346 (93.9%) had primary squamous cell carcinoma and 1193 (6.1%) had primary adenocarcinoma of the anus. The 5-year overall survival for stage II squamous cell carcinoma was 69.2%, and, for stage II adenocarcinoma, 5-year overall survival was 54.2% (p < 0.001). The 5-year overall survival for stage III squamous cell carcinoma was 55.2%, and, for stage III adenocarcinoma, 5-year overall survival was 32.9% (p < 0.001). On multivariable Cox regression, treatment with chemoradiation alone (HR, 0.67; p = 0.008) was associated with improved survival in squamous cell carcinoma. For the adenocarcinoma group, stage III disease (HR, 2.26; p < 0.001) and high tumor grade (HR, 1.59; p < 0.011) had a negative impact on survival, but there were no differences in survival based on the type of treatment received. LIMITATIONS: The National Cancer Database does not include information on specific chemotherapeutic or immunotherapy agents given to patients, nor does it provide the exact cause of death. CONCLUSIONS: Anal adenocarcinoma in comparison to anal squamous cell carcinoma had a lower 5-year overall survival stage for stage. Anal adenocarcinoma appears to be treated similarly to the rectal cancer paradigm, with frequent use of neoadjuvant chemoradiation. See Video Abstract at http://links.lww.com/DCR/B50. PATRONES DE EL CUIDADO Y COMPARACIÓN DE RESULTADOS ENTRE EL CARCINOMA DE CÉLULAS ESCAMOSAS ANAL PRIMARIO Y EL ADENOCARCINOMA ANAL: El tratamiento del adenocarcinoma del ano puede ser un desafío ya que hasta la fecha, hay pocos datos sobre los resultados y las tendencias en su tratamiento.Comparar y analizar los patrones de el cuidado y resultados de supervivencia de pacientes con carcinoma anal de células escamosas y adenocarcinoma anal.Este fue un estudio retrospectivo.Este estudio se realizó utilizando la Base de Datos Nacional de Cancer (National Cancer Database, NCB).Seleccionamos un total de 19,539 pacientes entre el 2004-2014 con carcinoma de células escamosas en estadio II-III o adenocarcinoma del ano.Los grupos de tratamiento analizados fueron solo cirugía, quimiorradiación neoadyuvante seguida por cirugía, cirugía seguida por quimiorradiación adyuvante o quimiorradiación definitiva.Se compararon los factores clínicos y de pacientes entre los dos grupos. Se utilizaron modelos de regresión de riesgos proporcionales de Kaplan-Meier y Cox para evaluar la supervivencia general.18,346 (93.9%) tenían carcinoma primario de células escamosas y 1,193 (6.1%) tenían adenocarcinoma primario del ano. La supervivencia global a 5 años para el carcinoma de células escamosas en estadio II fue del 69.2% y para el adenocarcinoma en estadio II fue del 54.2% (p < 0.001). La supervivencia global a cinco años para el carcinoma de células escamosas en estadio III fue del 55.2% y para el adenocarcinoma en estadio III fue del 32.9% (p < 0.001). En la regresión de Cox multivariable, el tratamiento con quimiorradiación sola (proporción de riesgo 0.67, p = 0.008) se asoció con una mejor supervivencia en el carcinoma de células escamosas. Para el grupo de adenocarcinoma, la enfermedad en estadio III (proporción de riesgo 2.26, p < 0.001) y el alto grado tumoral (proporción de riesgo 1.59, p < 0.011) tuvieron un impacto negativo en la supervivencia, pero no hubo diferencias en la supervivencia según el tipo de tratamiento recibido.La Base de Datos Nacional de Cancer no incluye información sobre agentes quimioterapéuticos o de inmunoterapia específicos que se administran a los pacientes, ni proporciona la causa exacta de la muerte.El adenocarcinoma anal en comparación con el carcinoma anal de células escamosas tuvo una supervivencia general inferior a 5 años, etapa por etapa. El adenocarcinoma anal parece tratarse de manera similar al paradigma del cáncer rectal, con el uso frecuente de quimiorradiación neoadyuvante. Vea el video del resumen en http://links.lww.com/DCR/B50.

Survival benefits and predictors of use of chemoradiation compared with radiation alone for early stage (T1-T2N0) anal squamous cell carcinoma.

BACKGROUND: Standard of care treatment for anal squamous cell carcinoma (SCC) is concurrent chemoradiation (CRT). However, the necessity of CRT over radiation alone for T1-2N0 disease is less certain. METHODS: The National Cancer Database (NCDB) was queried to identify patients who received CRT, defined as initiation of chemo and RT within 14 days of each other, or RT alone (without any chemo during initial treatment phase) for cT1-2N0M0 SCC of the anus. The cohort was limited to patients less than 70 years old with Charlson-Deyo Comorbidity Index of 0, receiving a radiation dose range of 4,500-5,940 cGy. Univariable and multivariable logistic regression were performed to assess for predictors of CRT usage. Five-year overall survival (OS) was analyzed using the Kaplan-Meier method with the log rank test both for the full cohort and then on the subsets of T1 and T2 patients. RESULTS: We identified 4,564 patients, of whom 4,371 (95.8%) received CRT and 193 (4.2%) received RT alone. Median follow up was 49.8 months. About 33.5% of patients had cT1N0 disease, while 66.5% of patients had cT2N0 disease. On multivariable logistic regression, patients were more likely to receive CRT if they had T2 disease [OR 2.318 (1.732-3.102), P<0.0001]. Five-year OS was 86.6% for CRT and 79.1% for RT (P=0.001). For T1 patients, 5-year OS was 90.3% with CRT and 84.7% with RT (P=0.114). For T2 patients, 5-year OS was 84.7% with CRT and 72.8% with RT (P<0.0001). Multivariable Cox regression analysis confirmed association between OS and CRT use [HR 0.588 (95% CI: 0.430-0.804), P=0.001]. CONCLUSIONS: The vast majority of patients under age 70 without significant comorbidities are treated with CRT over radiation alone for early stage anal SCC, with better survival associated with CRT.

Prognostic Differences: Epstein-Barr Virus-Associated Primary Leiomyosarcoma of the Spine Versus Spinal Leiomyosarcoma Metastases.

OBJECTIVE: The authors studied 6 cases of osseous leiomyosarcoma of the spine. Two of these cases were of immunocompromised human immunodeficiency virus (HIV)-positive patients with Epstein-Barr virus (EBV)-associated primary vertebral leiomyosarcomas. The remaining 4 cases were of patients with leiomyosarcoma metastases to the spine. METHODS: Each patient underwent surgical resection of their vertebral mass; however, the patients with the EBV-associated tumors had the best postoperative prognosis. RESULTS: The HIV-positive patients have had no further local recurrence, while the other 4 patients had rapid local recurrences requiring multiple surgical interventions. Furthermore, the patients living with HIV have lived longer with fewer leiomyosarcoma-related health complications. CONCLUSIONS: These findings suggest that EBV-associated vertebral leiomyosarcoma is of a less aggressive variety than metastatic leiomyosarcoma of the spine.

Therapy-related myelodysplastic syndromes, or are they?

The incidence of therapy-related myelodysplastic syndromes (t-MDS) is increasing as the number of cancer survivors is increasing. While t-MDS is currently defined descriptively by prior receipt of chemotherapy and/or radiotherapy, some forms of MDS that occur post localized radiation monotherapy, biologically and clinically resemble de novo (d)-MDS more than t-MDS, and therefore may not be truly therapy-related. Although patients with t-MDS, as a group, fare worse than patients with d-MDS, a variation in individual outcomes of patients with t-MDS has increasingly been appreciated. As such, accurate risk stratification is important for counseling of patients and for clinical decision making. Most of the current clinical tools used for prognostication in t-MDS were developed for d-MDS and were not specifically validated in patients with t-MDS. The management of patients with t-MDS remains challenging, highlighting the importance of developing effective prevention strategies as well as newer, targeted, and rationally-designed therapeutic interventions.