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 Outcomes of Adjuvant Chemoradiation for Node-Positive Pancreatic Adenocarcinoma.

PURPOSE: The literature has been conflicting on the superiority of adjuvant chemoradiation over chemotherapy for node-positive adenocarcinoma of the pancreas following definitive surgery. We aimed to evaluate the patterns of care and outcomes of these two treatment options using the National Cancer Database (NCDB). METHODS: Patients diagnosed with non-metastatic, node-positive adenocarcinoma of the pancreas from 2006 to 2014 who received oncologic resection with negative margins were identified in the NCDB. Patient- and clinical-related factors were compared between those who received adjuvant chemotherapy alone (aC) versus adjuvant chemoradiation (aCRT). Univariable and multivariable logistic regression was performed to assess for predictors of adjuvant chemoradiation use. The Kaplan-Meier method was used to assess overall survival (OS) and Cox regression analysis was used to assess impact of covariables on OS. RESULTS: There were 3609 patients who met the study criteria, of which 2988 (82.8%) received chemotherapy alone and 621 (17.2%) who received chemoradiation. Median follow up for living patients was 33.8 months (IQR 22-51). On multivariable logistic regression, those who received treatment in more recent years of diagnoses (OR 0.21-0.37, p < 0.001) were less likely to receive aCRT over aC. Two-year OS for those who received chemo alone was 44.9% and for chemoradiation was 42.6% (p = 0.169). This finding was sustained on multivariable survival analysis (HR 0.99, p = 0.867). CONCLUSIONS: Adjuvant chemotherapy alone for adenocarcinoma of the pancreas is the predominant treatment of choice among US hospitals. There was no overall survival benefit noted in those who were treated with adjuvant chemoradiation.

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.

Patterns of care and outcomes of adjuvant therapy for high-risk head and neck cancer after surgery.

BACKGROUND: Postoperative chemoradiotherapy (CRT) is considered standard of care in patients with locally advanced head and neck cancer with positive margins and/or extracapsular extension (ECE). METHODS: The National Cancer Data Base (NCDB) was queried to identify patients with squamous cell carcinoma of the head and neck with stages III to IVB disease or with positive margins and/or ECE diagnosed between 2004 and 2012 receiving postoperative radiotherapy (RT). Using univariable and multivariable logistic and Cox regression, we assessed for predictors of CRT use and covariables impacting overall survival (OS), including in a propensity-matched subset. RESULTS: Of 12 224 patients, 67.1% with positive margins and/or ECE received CRT as well as 54.0% without positive margins and/or ECE. The 5-year OS was 61.6% for RT alone versus 67.4% for CRT. In the propensity-matched cohort, OS benefit persisted with CRT, including in a subset with positive margins and/or ECE but not without. CONCLUSION: Postoperative CRT seems underutilized with positive margins and/or ECE and overutilized without positive margins and/or ECE. The CRT was associated with improved OS but the benefit persisted only in the subset with positive margins and/or ECE.

Impact of Adjuvant Radiotherapy for Malignant Salivary Gland Tumors.

Objective Using the National Cancer Database (NCDB), we investigated the characteristics, outcomes, and benefits of adjuvant therapy for patients diagnosed with malignant salivary gland tumors between 2004 and 2012. Study Design Retrospective analysis. Setting NCDB. Subject and Methods The cases of patients diagnosed with a nonmetastatic major salivary gland tumor who underwent resection between 2004 and 2012 were abstracted from the NCDB. Patients were further included if they had pT1-4NX-1M0 high-grade disease or pT3-4NX-0M0 or pT1-4N1M0 low-grade disease. Patients were identified as having no postoperative radiation therapy or having received postoperative radiation therapy to a dose of 5000 and 7000 cGy to the head and neck region or the parotid region, and their characteristics and outcomes were compared. Results During the study period, 4068 patients met the inclusion criteria for this analysis, of which 2728 (67.1%) received postoperative radiation and 1340 (32.9%) did not. With a median follow-up of 49.1 months, there was a significant improvement in overall survival associated with those receiving postoperative radiation (5 years, 56% vs 50.6%). On multivariable analysis, radiation utilization (hazard ratio, 0.78; 95% CI, 0.71-0.86; P < 0.001) and female sex (hazard ratio, 0.88) were associated with improved survival. When the analysis was limited to patients ≤65 years old, the survival benefit was persistent on multivariable analysis. Conclusion In conclusion, in this large NCDB study of 4068 patients with locally advanced malignant salivary gland carcinoma, administering adjuvant radiotherapy was associated with improved overall survival.

Comparison of neoadjuvant vs concurrent/adjuvant androgen deprivation in men with high-risk prostate cancer receiving definitive radiation therapy.

PURPOSE: It is unknown whether there is a benefit to starting androgen deprivation therapy (ADT) prior to rather than concurrently with definitive radiation therapy in men with high-risk prostate cancer. We studied the National Cancer Data Base to determine whether the timing of ADT impacts survival. METHODS: Men diagnosed with high-risk prostate adenocarcinoma who received external beam radiation therapy (EBRT) to a dose of 70-81 Gy along with ADT from 2004-2011 were included. Those who started ADT 42-90 days before EBRT were identified as having received neoadjuvant hormonal therapy (N-HT) and those who received ADT from 14 days before their radiation until 84 days after the start of EBRT were categorized as receiving concurrent/adjuvant treatment (C-HT). We used the log-rank test to compare Kaplan-Meier survival curves and multivariable Cox regression to assess the impact of covariables on overall survival (OS). RESULTS: Among 11,491 included patients, those receiving N-HT were 1 year older (p<0.001) and more likely to have Gleason 8-10 disease (p = 0.01) and cT3-4 disease (p = 0.002). Men receiving N-HT had a 5-year and median OS of 80.6% and 111.4 months, respectively, compared to 78.3% and 108.9 months, respectively, in those receiving C-HT (p = 0.03). This benefit remained significant on multivariable analysis (hazard ratio 0.86, 95% confidence interval 0.77-0.96, p = 0.008). Duration of ADT was not available to report. CONCLUSIONS: External beam radiation therapy with N-HT was associated with improved overall survival compared to C-HT. This study is hypothesis-generating and further studies are needed to best qualify the sequencing of hormone therapy with the duration of treatment.

Targeting Survivin Enhances Chemosensitivity in Retinoblastoma Cells and Orthotopic Tumors.

Treatments for retinoblastoma (Rb) vary depending on the size and location of the intraocular lesions and include chemotherapy and radiation therapy. We examined whether agents used to treat Rb induce a pro-survival phenotype associated with increased expression of survivin, a member of the inhibitor of apoptosis family of proteins. We document that exposure to carboplatin, topotecan or radiation resulted in elevated expression of survivin in two human Rb cell lines but not in normal retinal pigmented epithelial (RPE) cells. Cellular levels of survivin were attenuated in Rb cells exposed to an imidazolium-based survivin suppressant, Sepantronium bromide (YM155). Protein expression patterns of survivin in RPE cells were not altered following treatment protocols involving exposure to YM155. Including YM155 with chemotherapy or radiation increased levels of apoptosis in Rb cells but not in RPE cells. Intraocular luciferase expressing Rb tumors were generated from the Rb cell lines and used to evaluate the effects of carboplatin and YM155 on in-vivo survivin expression and tumor growth. Carboplatin induced expression of survivin while carboplatin combined with YM155 reduced survivin expression in tumor bearing eyes. The combination protocol was also most effective in reducing the rate of tumor regrowth. These results indicate that targeted inhibition of the anti-apoptotic protein survivin provides a therapeutic advantage for Rb cells and tumors treated with chemotherapy.

Stereotactic radiosurgery to the resection cavity for brain metastases: prognostic factors and outcomes.

BACKGROUND: Adjuvant stereotactic radiosurgery (SRS) alone after surgical resection is increasingly being used to provide excellent local control while avoiding the side effects of whole brain radiation therapy (WBRT). We report our ten year experience using this treatment scheme. PURPOSE/OBJECTIVES: To determine the rates and any correlates of local control, distant brain failure, and overall survival using SRS alone to the resection cavity. MATERIALS/METHODS: We performed a retrospective analysis of 509 patients with brain metastasis who underwent Gamma Knife SRS at our institution between 2003 and 2013. Of this group 85 patients were identified that had resection of the metastasis and subsequent SRS to the cavity. Mean dose to the resection cavity was 17.3 Gy (range 14-20) to an average volume of 12cc (range 0.3-83cc). Multiple patient, tumor, and treatment specific factors were collected for analysis (see Table 1). Vital statistics were provided by our institution's tumor registry. The primary endpoint of our analyses was recurrence free survival (RFS); defined as the duration in time between the date of SRS and any local or distant brain tumor recurrence. RESULTS: With a median follow up of 16.4 months, the overall local and distant brain failure at 12 months was 13% (95%CI 5%-21%) and 51% (95%CI 37%-64%) respectively. RPA was class 1 (5%), 2 (75%), and 3 (20%). The median overall survival (OS) was 20 months. The median RFS was 24 months with radiosensitive tumors: non small cell lung cancer (n=12), breast (n=16), gastrointestinal (n=7), small cell lung cancer (n=1), and other (n=9) compared to 5.6 months (p=0.006) in radioresistant tumors: melanoma (n=33), sarcoma (n=1), and renal cell carcinoma (n=6). Median OS for radioresistant and radiosensitive patients was 12 vs 25 months respectively (p=0.11). Additionally, there was a significant improved survival difference seen amongst those who had a gross total resection (GTR, n=46) compared to a sub total resection (n=39) with median OS of 27 vs 16 months (p=0.020) respectively. Radiographic changes suggestive of radiation necrosis were present in 6 patients, 2 of which were determined histiopathologicaly after surgical intervention. Due to the limited number of local recurrence events (n=10), there was insufficient power to analyze prognostic factors for local recurrence. CONCLUSIONS: Our results compare favorably with multiple other institution experiences showing excellent local control with SRS to the resection cavity following resection. Radioresistant histologies were associated with a worse RFS. Patients undergoing GTR had a significantly longer OS than those with STR. At our institution we continue to offer patients SRS to the resection cavity for those with good performance status and limited brain metastases.