Patterns of Care and Outcomes for Small Cell Carcinoma of the Cervix: A National Retrospective Analysis of 542 Cases.

PURPOSE: Small cell carcinoma of the cervix (SCCC) represents 1% to 5% of cervical cancers, with limited data on management and outcomes. We evaluated patterns of care and outcomes for SCCC using the National Cancer Database. METHODS AND MATERIALS: This retrospective cohort study of SCCC (2004-2011) included 542 cases. Patient demographic, diagnosis, treatment information, and overall survival (OS) were compared with descriptive statistics, logistic regression, Kaplan-Meier, and Cox models. Clinical reasoning was used to select variables for multivariable models to avoid overfitting. RESULTS: SCCC had more comorbidities, higher grade, and advanced stage than other histologies. SCCC received neoadjuvant chemotherapy (36%) more often than squamous cell carcinoma (23%) and adenocarcinoma (13%, P < .001). SCCC had worse OS across all stages (P < .001). Looking at SCCC alone, patients who received chemoradiation (CRT) (with external beam and brachytherapy) and those who received chemotherapy and surgery (without RT) had similar OS (median OS 44 vs 47 months; P = .7) on Kaplan-Meier. Patients receiving CRT were more likely to have stage II or III and N+ disease (P < .001). When evaluating chemoradiation, the addition of brachytherapy resulted in improved median OS (35 vs 19 months; P = .001) regardless of surgical resection status and controlling for age and stage. Even after controlling for stage, age, and comorbidities, the addition of brachytherapy was associated with a 40% improvement in OS (hazard ratio 1.4, 95% confidence interval 1.0-2.0). CONCLUSIONS: SCCC patients benefit from chemotherapy with aggressive local treatment. Patients who receive CRT that included brachytherapy did as well as patients who received chemotherapy followed by surgery. Brachytherapy remains an essential component in the treatment of SCCC with CRT.

Building a palliative radiation oncology program: From bedside to B.E.D.

A growing body of evidence supports the integration of palliative care with standard cancer treatments. In these situations, patients often experience a better quality of life, better quality of care, decreased cost, and, in some cases, improved survival with the addition of palliative care services to traditional treatment pathways. In this manuscript, we explore the integration of radiation oncology at palliative care. First, we discuss the impetus for change at Vanderbilt University and the inception of Vanderbilt's inpatient Palliative Radiation Oncology Service at Vanderbilt. Second, we discuss the growth of palliative care and how this invites innovative collaborative care delivery models. As you will see, this mutually beneficial relationship expands new service lines, brings radiation oncology interventions and expertise to more patients seen by palliative care specialists, and improves overall care for some of the sickest, most vulnerable patients in the health care system. As we move away from fee-for-service and toward bundled and global-based strategies, there will be further emphasis on supportive and palliative care services at the end of life. Understanding how radiation oncology can evolve is ever more relevant.

Selective omission of level V nodal coverage for patients with oropharyngeal cancer: Clinical validation of intensity-modulated radiotherapy experience and dosimetric significance.

BACKGROUND: We sought to validate the consensus recommendation and assess dosimetric significance of selective omission of nodal level V from intensity-modulated radiotherapy (IMRT) clinical target volume (CTV) for oropharyngeal cancer. METHODS: IMRT plans and clinical outcomes for 112 patients with oropharyngeal cancer (nodal classification N0-N2b) were analyzed for coverage of ipsilateral and contralateral nodal level V. Additionally, new IMRT plans were generated in 6 randomly selected patients to assess its dosimetric impact. RESULTS: With median follow-up of 3.4 years, there were no failures identified in nodal level V with or without nodal level V omission. Upon dosimetric evaluation, significant reduction in integral dose, V10 Gy , V20 Gy , V30 Gy , V40 Gy , and V50 Gy was observed by excluding unilateral and bilateral level V from the CTV. CONCLUSION: We clinically validate the consensus recommendation for selective omission of level V nodal coverage in IMRT planning of patients with oropharyngeal cancer and demonstrate significant dosimetric advantages.

Blood outgrowth endothelial cells increase tumor growth rates and modify tumor physiology: relevance for therapeutic targeting.

Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm3) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the oxygenation and subsequent radiation response of tumors. We surmise that these cells are preferentially stimulated to divide in the tumor microenvironment, thereby inducing the significant increase in tumor growth observed and that the use of injected BOECs could be a viable approach to modulate the tumor microenvironment for therapeutic gain. Conversely, agents or approaches to block their recruitment and integration of BOECs into primary or metastatic lesions may be an effective way to restrain cancer progression before or after other treatments are applied.