Mark J. Amsbaugh

Tumor bed radiosurgery: an emerging treatment for brain metastases.

While typically used for treating small intact brain metastases, an increasing body of literature examining tumor bed directed stereotactic radiosurgery (SRS) is emerging. There are now over 1000 published cases treated with this approach, and the first prospective trial was recently published. The ideal sequencing of tumor bed SRS is unclear. Current approaches include, a neoadjuvant treatment before resection, alone as an adjuvant after resection, and following surgery combined with whole brain radiotherapy either as an adjuvant or salvage treatment. Based on available evidence, adjuvant stereotactic radiosurgery improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated. While results from published series vary, heterogeneity in both patient populations and methods of reporting results make comparisons difficult. Additional prospective data, including randomized trials are needed to confirm equivalent outcomes to the current standard of care. We review the current literature, identify areas of ongoing contention, and highlight ongoing studies.

Computed tomography–planned interstitial brachytherapy for locally advanced gynecologic cancer: Outcomes and dosimetric predictors of urinary toxicity

PURPOSE To identify dosimetric predictors of outcome and toxicity in patients receiving CT-planned interstitial brachytherapy (ISBT) for gynecologic cancers. METHODS AND MATERIALS Patients who received ISBT between 2009 and 2014 were reviewed. Demographic, disease specific, treatment, and toxicity data were collected. Logistic regression was used to model toxicity. A least absolute shrinkage and selection operator penalty was used to identify relevant predictors. Receiver operating characteristic curves were used to analyze the relation between dosimetric factors and urinary toxicity. RESULTS Seventy-three patients received ISBT (21 at time of cancer recurrence and 52 at the first presentation). Thirty-six patients had cervical cancer, 16 had vaginal cancer, 13 had uterine cancer, and 8 had vulvar cancer. ISBT was performed using both high-dose-rate and low-dose-rate 192Ir sources (27 low dose rate and 46 high dose rate). With a median followup of 12 months, Grade 3 vaginal, urinary, and rectal toxicity occurred in 17.8%, 15.1%, and 6.8% of patients, respectively. No patients experienced Grade 4 or 5 toxicity. Dose to 0.1cc of urethra predicted for development of Grade 3 urinary toxicity (area under the curve of 0.81; 95% confidence interval: 0.66, 0.96). A 10% probability of a Grade 3 urinary toxicity associated with a dose of 23.1 equivalent dose in 2 Gy fractions (95% confidence interval: 9.51, 36.27 equivalent dose in 2 Gy fractions). CONCLUSIONS ISBT is a safe treatment for gynecologic malignancies. The dose to 0.1cc significantly predicts for severe urinary toxicity. Our data suggests that dose to a small urethral volume may be the most significant predictor of urinary toxicity in patients receiving ISBT for gynecologic cancer.

High-dose versus weekly cisplatin definitive chemoradiotherapy for HPV-related oropharyngeal squamous cell carcinoma of the head and neck

OBJECTIVES To compare the outcomes and toxicity of high-dose cisplatin (HDC) versus weekly cisplatin (WC) definitive chemoradiotherapy (CRT) for patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (SCCOPx). METHODS All patients with p16 positive SCCOPx treated with definitive CRT with cisplatin between 2010 and 2014 at a single institution were retrospectively reviewed. CTCAE v 4.03 toxicity criteria were used. The Kaplan-Meier method was used to estimate event-free survival (EFS) and the overall survival (OS). RESULTS Of the 55 patients included, 22 were patients treated with HDC at dose of 100mg/m2 on days 1 and 22; and the remaining 33 patients were treated with WC at 40mg/m2. Both cohorts received a median total dose of cisplatin of 200mg/m2. At median follow-up of 31months, there was one local failure and no distant failures in the HDC cohort. In the WC group, there were 6 total failures (2 local, 4 distant). Estimated 2-year EFS was better in HDC cohort as compared to WC (96% vs. 75%; p=0.04). There was no significant difference in 2-year OS (95% vs. 94%; p=0.40). Weight loss, gastric tube dependence at six months, acute renal injury and grade 3 or 4 hematological toxicity were all similar between both groups. CONCLUSIONS HPV-related SCCOPx treated with definitive CRT with either HDC or WC had similar toxicity profile. HDC had better EFS when compared with WC and this seems to be driven by increased distant failure rates, although the OS was similar.

Patterns of care and predictors of adjuvant therapies in elderly patients with glioblastoma: An analysis of the National Cancer Data Base

The objectives of this study were to characterize patterns of care and to identify predictors for adjuvant therapy in elderly patients with glioblastoma in the modern era. METHODS. The National Cancer Data Base was queried for patients aged 70 years and older with glioblastoma diagnosed from January 1, 2004 through December 31, 2012. Multinomial logistic regression was used to identify predictors for receiving adjuvant therapy. Survival outcomes were estimated using the Kaplan‐Meier method and were analyzed using Cox regression models and the log‐rank test.

Patterns of Care and Outcomes of Adjuvant Radiotherapy for Meningiomas: A Surveillance, Epidemiology, and End Results and Medicare Linked Analysis

Background: The role of adjuvant stereotactic radiosurgery (SRS) and fractionated radiotherapy (XRT) are unknown in patients with resected meningiomas. Objective: To identify patterns of care and outcomes of adjuvant radiotherapy for meningiomas in the Linked Surveillance, Epidemiology, and End Results (SEER) Medicare data. Methods: A total of 1,964 patients older than 66 years included in the SEER-Medicare data, who were diagnosed with meningioma, and underwent craniotomy were included for analysis. Results: Patients were less likely to receive adjuvant therapy if they were older than 75 (OR 0.730, 95% CI 0.548-0.973), female sex (OR 0.731, 95% CI 0.547-0.978), or unmarried (OR 0.692, 95% CI 0.515-0.929). Patients were more likely to receive adjuvant treatment for Grade II/III tumors (OR 5.586, 95% CI 2.135-13.589), tumors over 5 cm (OR 1.850, 95% CI 1.332-2.567), or partial resection (OR 3.230, 95% CI 2.327-4.484). Yearly between 2000 and 2009, 10.65 – 19.77% of patients received adjuvant therapy. Although no survival benefit was seen with the addition of adjuvant therapy (p = 0.1236), the subgroup of patients receiving SRS had a decreased risk of death compared to those receiving surgery alone (aHR 0.544, 95% CI 0.318 – 0.929). Conclusion: Utilization of adjuvant XRT and SRS remained stable between 2000 and 2010. Male sex, young age, marriage, partial resection, Grade II/III tumors, and large tumors predicted the use of adjuvant therapy. For all patients, SRS decreased the risk of death compared to craniotomy alone.

Optimal epidural analgesia for patients diagnosed as having gynecologic cancer undergoing interstitial brachytherapy

STUDY OBJECTIVE To determine the optimal epidural analgesia for patients receiving interstitial brachytherapy (ISBT) for gynecologic cancers. DESIGN Retrospective analysis. SETTING Operating room and hospital ward. PATIENTS Seventy-three patients diagnosed as having gynecologic cancer and undergoing ISBT. INTERVENTIONS Twelve patients received ropivacaine alone, 14 patients received ropivacaine with fentanyl, and 45 patients received ropivacaine with hydromorphone by epidural infusion. MEASUREMENTS Numeric Rating Scale pain scores, amounts of nonnarcotic and narcotic pain medications used in intravenous morphine equivalents (IVMEs), and amount of antiemetic or antipruritic medications used. MAIN RESULTS Patients receiving ropivacaine alone had higher pain scores the morning of day 2 (4.2 vs 1.71 vs 0.6, P=.001), the afternoon of day 2 (4.9 vs 2.5 vs 1.7, P=.005), and the night of day 2 (2.4 vs 2.0 vs 0.6, P<.001). Patients receiving opioids in their epidural had lower pain scores on the night of placement (P=.050), the morning of day 2 (P<.001), the afternoon of day 2 (P=.002), and the night of day 2 (P<.001). Patients receiving ropivacaine alone used more oral narcotics than did those receiving ropivacaine with fentanyl or ropivacaine with hydromorphone on day 3 (5.9 vs 3.8 vs 2.8mg IVME) and received more intravenous opioids day 1 (5.8 vs 0.0 vs 0.7mg IVME, P=.004) and day 2 (20.6 vs 4.8 vs 1.0mg IVME, P=.042). There were no differences in antiemetic or diphenhydramine usage at any time point. No epidural complications occurred. CONCLUSIONS For patients receiving ISBT for gynecologic cancer, epidural analgesia provides safe and effective pain control. Combined modality epidural analgesia improves pain control and lessens oral and intravenous opioid requirements without increased risk of adverse effects compared with epidural analgesia with local anesthetic alone.

Second Neoplasms After Successful Treatment for Pediatric Central Nervous System Tumors

As survival rates following treatment for pediatric central nervous system tumors continue to improve, it is now clear that survivors of childhood cancer are at risk for a wide range of health, neurocognitive, social, and psychiatric issues. Perhaps the most significant and damaging complication facing survivors of childhood cancers is diagnosis of a second neoplasm. The development of a second neoplasm is a multifactorial process that is influenced by cancer histology, genetics, treatment technique and intensity, and environmental factors. These are a group of histologically diverse cancers that can occur at any location in the body with varied latency times. Many secondary malignant neoplasms have an extremely poor prognosis. While radiotherapy dose and field design been associated with second neoplasm development, new treatment strategies and technologies such as proton therapy have the potential to significantly reduce this devastating complication of treatment. As our ability to understand and quantify the factors that influence risk improve, models accurately predicting individual risk may be incorporated into treatment selection.

Effect of time to simulation and treatment for patients with oropharyngeal cancer receiving definitive radiotherapy in the era of risk stratification using smoking and human papillomavirus status

The effect of increasing time to definitive radiotherapy (RT) for patients with oropharyngeal squamous cell carcinoma (SCC) is unknown.

Neck dissection for unknown cancer of the head and neck in the era of chemoradiation

PURPOSE To report outcomes for patients with cervical lymph node metastases from an unknown primary site of the head and neck treated with either non-operative therapy or neck dissection followed by adjuvant therapy. MATERIALS AND METHODS All patients with squamous cell carcinoma of an unknown primary site of the head or neck seen between 2003 and 2013 were reviewed. The Kaplan-Meier method was used to estimate overall survival, local recurrence free survival, loco-regional recurrence free survival, and progression free survival. The log-rank test and proportional hazards regression were used to analyze factors influencing outcomes. RESULTS Of 2258 patients with a new diagnosis of head and neck cancer, no primary site was identified in 66 patients. Twenty-nine patients were treated with definitive non-operative therapy (15 with chemoradiation and 14 with radiation alone). Thirty-seven patients received an upfront neck dissection followed by adjuvant radiation or chemoradiation. Three-year loco-regional recurrence free survival, progression free survival, and overall survival were 55.9%, 55.4%, and 69.4% respectively. Patients treated with preoperative neck dissection had improved local recurrence free survival (96.7% vs 54.1%, p=0.003) and loco-regional recurrence free survival (82.2% vs 46.4%, p=0.068) compared to patients treated with definitive chemoradiation with no difference in overall survival (p=0.641). CONCLUSIONS Neck dissection improved local and regional control but not overall survival in patients with unknown primary squamous cell carcinoma of the head and neck over non-operative therapy alone.

Organ preservation with neoadjuvant chemoradiation in patients with orbit invasive sinonasal cancer otherwise requiring exenteration.

Purpose We sought to determine if organ preservation (OP) with neoadjuvant chemoradiation (CRT) was feasible in patients with sinonasal cancer determined to require exenteration. Materials and Methods Twenty patients were determined to require exenteration for definitive treatment from 2005 to 2014. Fourteen patients underwent OP and 6 patients received exenteration with adjuvant CRT. Exenteration free survival (EFS), locoregional control (LRC), progression-free survival (PFS), and overall survival (OS) were estimated. Results Five patients (36%) receiving OP had complete disease response at time of surgery. With a median follow-up of 18.8 months, EFS was 62% at 2 years for patients undergoing OP. At 2 years, there were no significant differences in LRC, PFS or OS (all all p > 0.050) between the groups. Less grade 3 or greater toxicity was seen in patients undergoing OP (p = 0.003). Visual function was preserved in all patients undergoing OP. Conclusion For patients with sinonasal cancer, OP may avoid exenteration, offering similar disease control and improved toxicity.