James E. Bates

Malignant Peripheral Nerve Sheath Tumors (MPNST): A SEER Analysis of Incidence Across the Age Spectrum and Therapeutic Interventions in the Pediatric Population

Malignant peripheral nerve sheath tumors (MPNST) are very rare in the general population and challenging to treat. A paucity of data exists regarding the incidence of MPNST across all age groups and treatment outcomes in the pediatric population. We aimed to characterize both using the Survival, Epidemiology, and End Results (SEER) database.

The Benefit of Adjuvant Radiotherapy in High-grade Nonmetastatic Retroperitoneal Soft Tissue Sarcoma: A SEER Analysis.

Objectives: Controversy persists on the use of adjuvant radiotherapy (RT) in patients with retroperitoneal sarcoma (RPS). High-grade disease is known to be associated with decreased local control and overall survival (OS). Because RT has proven beneficial for local control and OS in patients with high-grade extremity soft tissue sarcoma, we evaluated the efficacy of adjuvant RT in high-grade RPS. Methods: The Surveillance, Epidemiology, and End Results database was used to identify patients with pathology-confirmed RPS from 1973 to 2010. Clinical characteristics and outcomes were analyzed. Results: Of 480 total patients, 144 (30.0%) received postoperative radiation. Patients who received adjuvant RT had improved median OS (36 mo) compared with those who did not (27 mo, hazard ratio [HR]=0.79, P=0.023). On multivariate analysis the use of adjuvant RT (HR=0.80; 95% confidence interval [CI], 0.65-0.98; P=0.029), male sex (HR=1.32; 95% CI, 1.10-1.59; P=0.003), age above 65 years (HR=1.38; 95% CI, 1.15-1.67; P=0.001), and increasing the Surveillance, Epidemiology, and End Results historical stage (HR=1.46; 95% CI, 1.21-1.76; P<0.001) were all prognostic factors for OS. Conclusions: In a large retrospective analysis, postoperative RT improved OS in high-grade RPS patients. As such, adjuvant RT should be strongly considered in all patients with high-grade RPS. The optimal timing of RT relative to surgery requires further study.

Radiotherapy for Brain Metastases From Renal Cell Carcinoma in the Targeted Therapy Era: The University of Rochester Experience

Objectives: Radiotherapy remains the standard approach for brain metastases from renal cell carcinoma (RCC). Kinase inhibitors (KI) have become standard of care for metastatic RCC. They also increase the radiosensitivity of various tumor types in preclinical models. Data are lacking regarding the effect of KIs among RCC patients undergoing radiotherapy for brain metastases. We report our experience of radiotherapy for brain metastatic RCC in the era of targeted therapy and analyzed effects of concurrent KI therapy. Methods: We retrospectively analyzed 25 consecutive patients who received radiotherapy for brain metastases from RCC with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both. Kaplan-Meier rates of overall survival (OS) and brain progression-free survival (BPFS) were calculated and univariate analyses performed. Results: Lower diagnosis-specific graded prognostic assessment (DS-GPA) score and multiple intracranial metastases were associated with decreased OS and BPFS on univariate analysis; DS-GPA is also a prognostic factor on multivariate analysis. There was no significant difference in OS or BPFS for SRS compared with WBRT or WBRT and SRS combined. The concurrent use of KI was not associated with any change in OS or BPFS. Conclusions: This hypothesis-generating analysis suggests among patients with brain metastatic RCC treated with the most current therapies, those selected to undergo SRS did not experience significantly different survival or control outcomes than those selected to undergo WBRT. From our experience to date, limited in patient numbers, there seems to be neither harm nor benefit in using concurrent KI therapy during radiotherapy. Given that most patients progress systemically, we would recommend considering KI use during brain radiotherapy in these patients.

Spinal drop metastasis in myxopapillary ependymoma: a case report and a review of treatment options

Myxopapillary ependymoma (MPE) is a World Health Organization grade I ependymoma that is quite rare and generally thought to be benign. Possible drop metastasis from MPE has been reported three times in the literature; in each case there were cotemporaneous additional MPE lesions. We report the case of a man who had a piecemeal gross total resection of a MPE at L1-L3 followed by adjuvant external beam radiotherapy (EBRT) who presented sixteen months later with a lesion in the thecal sac consistent with drop metastasis. A subtotal resection and adjuvant EBRT were performed. The patient has been disease-free in follow-up 27 months from the second surgery. A review of the literature regarding the treatment for MPE showed that gross total resection is optimal initial management. Several retrospective studies supported the role of adjuvant radiotherapy in enhancing local control and progression-free survival. Chemotherapy has a minimal role in the management of MPE.

Prognostic significance of sites of extrathoracic metastasis in patients with non-small cell lung cancer

BACKGROUND Metastatic non-small cell lung cancer (NSCLC) continues to have a poor prognosis despite recent advances in both targeted radiotherapy methodologies such as stereotactic body radiotherapy (SBRT) and immunotherapies. The impact of location of metastatic disease in patients with NSCLC has not been investigated; we aimed to investigate this using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS We included 39,910 patients from the SEER database treated for M1b NSCLC from 2010-2013. We identified patients with metastatic disease in the brain, lung, liver, and bone. We used Kaplan-Meier analyses and Cox proportional hazards models to assess the impact of varying sites of metastatic disease on overall survival (OS). RESULTS Patients with disease coded as in the brain without other disease in the lung, liver, or bone had improved OS relative to all other comers with M1b disease (HR =0.84, 95% CI, 0.84-0.90, P<0.001). Likewise, patients with disease coded as in the bone without other disease in the lung, liver, or brain had improved OS relative to all other comers with M1b disease (HR =0.89, 95% CI, 0.86-0.92, P<0.001). CONCLUSIONS This hypothesis-generating analysis suggests that patients with limited metastatic NSCLC to the bone or brain may particularly benefit from aggressive upfront therapies.

To Treat or Not to Treat? A Postmastectomy Question.

A 47-year-old premenopausal woman with no known family history of breast cancer and an unremarkable medical history presented to her primary care physician after palpating a mass in her left breast. A mammogram and ultrasound demonstrated a 3.2 1.3-cm mass at 3 o’clock, 4 cm from the nipple, in her left breast. A biopsy showed invasive ductal carcinoma, intermediate nuclear grade, with associated high-grade ductal carcinoma in situ (DCIS). Estrogen and progesterone receptors stained positive, HER2 was negative by FISH, and Ki67 was 25%. Breast MRI confirmed the primary mass and showed a 2-mm left internal mammary lymph node (Figs. 1A and 1B). A positron emission tomography scan was not performed because the small size of the internal mammary node precluded adequate sensitivity. The patient underwent mastectomy with axillary sentinel lymph node biopsy. Pathology revealed a unifocal 5.2-cm grade 2 invasive ductal carcinoma spanning the upper and lower outer quadrants, with associated intermediate-grade DCIS. Lymphovascular space invasion and perineural invasion were seen histologically. None of the 5 lymph nodes removed from the left axilla contained malignancy. The closest margin for both invasive disease and DCIS was 6 mm. Upon evaluation by a medical oncologist, an Oncotype-DX (Redwood City, CA) test was performed, with a score of 19. The patient completed 4 cycles of adjuvant docetaxel and cyclophosphamide and initiated 5 years of tamoxifen.

Pearls & Oy-sters: Cough headache secondary to Chiari malformation type I

Cough headache is a rare condition, but its presence should prompt thorough evaluation for intracranial pathology, given a high prevalence of secondary causes of headache in this population.

Repeat courses of SRS in patients initially treated with SRS alone for brain-metastatic melanoma

Aim Stereotactic radiosurgery (SRS) is often used in the treatment of brain metastatic melanoma. Little data exist regarding outcomes of repeat course of SRS in this population. We aimed to identify treatment outcomes and toxicities in melanoma patients treated with repeat SRS after upfront SRS. Patients & methods We reviewed ten consecutive patients treated with repeat SRS following upfront SRS alone for brain metastatic melanoma. Results The median overall survival from initial treatment was 17.5 months. The median overall survival from repeat SRS was 6.7 months with a 6-month local control rate of 80%. The majority of patients progressed systemically before death. Four patients reported six adverse events, all grade 1. Conclusion Prospective study regarding the safety and efficacy of repeat courses of SRS in patients with brain-metastatic melanoma, especially in combination with novel immunotherapies, is warranted.

Survival after subsequent non-Hodgkin's lymphoma and non-small cell lung cancer in patients with malignant thymoma.

BACKGROUND Survivors of malignant thymoma (MT) are at an increased risk of developing subsequent neoplasms. We compare overall survival (OS) between MT survivors who developed non-Hodgkins lymphoma (NHL) or non-small cell lung cancer (NSCLC), and patients with first primary NHL (NHL-1) or NSCLC (NSCLC-1), respectively. METHODS Using the population-based Surveillance, Epidemiology, and End Results (SEER) database for 1973 through 2013, 273,313 patients who had NHL-1, 21 patients with MT-NHL, 566,819 patients with NSCLC-1, and 38 patients with MT-NSCLC were identified. Univariate and multivariate models were used to assess the impact of various factors on OS. RESULTS The observed-to-expected ratio among MT patients was 2.63 [95% confidence interval (95% CI), 1.40-4.49; P<0.05] for NHL and 1.90 (95% CI, 1.33-3.63; P<0.05) for lung cancer. On univariate analysis, MT history did not worsen OS for NHL [hazard ratio (HR), 1.46; 95% CI, 0.87-2.47; P=0.16] or NSCLC (HR, 0.89; 95% CI, 0.61-1.29; P=0.53). On multivariate analysis, MT history was found to be an adverse prognostic indicator on OS for NHL (HR, 2.03; 95% CI, 1.20-3.42; P=0.008), but not NSCLC (HR, 0.87; 95% CI, 0.60-1.25; P=0.45). CONCLUSIONS Patients who develop NHL after MT have inferior survival than those with first primary NHL. A history of MT does not have an adverse prognostic impact on subsequent NSCLC. Clinicians must be aware of the intrinsic risk for subsequent malignancies after MT and the potential adverse impact of MT history on NHL prognosis but not NSCLC.