The Prognostic Significance of Facial Nerve Involvement in Carcinomas of the Parotid Gland.

IMPORTANCE AND BACKGROUND: Facial nerve (FN) palsy and perineural invasion (PNI) are adverse features in carcinomas of the parotid gland. FN sacrifice at the time of surgery is associated with significant morbidity. The role of adjuvant radiotherapy in patients with high-risk features, including FN involvement, remains unclear. OBJECTIVE: Analyze the disease-free survival (DFS) and overall survival (OS) and the impact of tumor characteristics, including FN involvement, for patients treated with surgical resection for carcinoma of the parotid gland. DESIGN: This is a retrospective chart review. SETTING: University of Utah and Intermountain Healthcare, Utah. PARTICIPANTS: A total of 129 patients who were treated with primary surgery for nonmetastatic primary malignancies of the parotid gland from 1988 to 2006. INTERVENTIONS: Parotidectomy with or without adjuvant therapy. MAIN OUTCOME(S) AND MEASURES: Kaplan-Meier analysis was used to obtain 5-year estimates of DFS and OS. Recurrence risk factors, particularly the impact of FN involvement, were analyzed. RESULTS: Five-year DFS and OS rates were 79% and 78%, respectively. Thirty-two (28%) patients developed recurrent disease. Disease recurrence occurred in 64% of patients with both FN palsy and PNI, in 43% with FN palsy without PNI, in 27% with only PNI, and in 16% without either feature. CONCLUSIONS AND RELEVANCE: FN involvement, particularly FN palsy, is a predictor of increased risk of recurrence and death. Radiotherapy cannot substitute for FN sacrifice in high-risk patients.

Toxicity and cost-effectiveness analysis of intensity modulated radiation therapy versus 3-dimensional conformal radiation therapy for postoperative treatment of gynecologic cancers.

OBJECTIVE: To evaluate toxicity and cost-effectiveness of intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) in the postoperative treatment of uterine and cervical cancer. METHODS: Between 2000 and 2012, eighty patients at our institution received post-hysterectomy 3DCRT (46) or IMRT (34) for uterine or cervical cancer. Baseline characteristics, outcome, and ≥CTCAE grade 2 toxicities were compared between the two groups. Predictors of toxicity-free survival were identified. A decision analysis model was designed to capture individual health states at 1, 2, and 3 years after treatment. Micro-costing technique and estimated quality-adjusted life years (QALYs) were used to calculate incremental cost-effectiveness ratio (ICER). RESULTS: Utilization of IMRT increased from 25% (2005-2007) to 75% (2008-2012). Recurrence-free and overall survival rates were not different between the two groups. Toxicity rates were reduced with IMRT versus 3DCRT (HR 0.42, p=0.04). Women who received IMRT had numerically lower rates of late gastrointestinal and genitourinary toxicity and significantly lower rates of late overall toxicity at 3 years (16% vs. 45%, p=0.04). On univariate analysis, IMRT was associated with decreased late toxicity (HR 0.43, p=0.04). Treatment costs were higher and toxicity costs were lower with IMRT. IMRT had an ICER of $235,233 (year 1), $114,270 (year 2), and $75,555 (year 3) per QALY gained. CONCLUSION: IMRT is associated with reduced late overall toxicity compared to 3DCRT without compromising clinical outcome. IMRT is not cost-effective during the early chronic toxicity phase, but it becomes more cost-effective over time.

Tumor control and incidence of radiation necrosis after reirradiation with stereotactic radiosurgery for brain metastases.

OBJECTIVES: To determine the ability of a second course of stereotactic radiosurgery (SRS) to control brain metastases as well as to document the incidence of radiation necrosis (RN) after reirradiation with SRS. METHODS AND MATERIALS: Between 2001 and 2010, 37 patients with 43 retreated lesions were treated with ≥2courses of SRS to the same brain metastasis. Patient, tumor, and treatment characteristics as well as follow-up data were collected. Magnetic resonance imaging was reviewed to assess tumor response to treatment. Development of RN, as confirmed by pathology or imaging, was recorded. Local control, overall survival, and predictors of RN were analyzed. RESULTS: The most common histology was melanoma (n=20, 47%) followed by lung (n=9, 21%), and breast (n=8, 19%) cancer. RN was identified in 7/43 (16%) lesions. Using a competing risk model for analysis, with death as the competing risk, the incidence of RN was 11.6% and 16.5% at 6 and 12 months, respectively, and the incidence of local failure was 16.7% and 19.4% at 6 and 12 months, respectively. There was not a statistically significant association between radiation dose, mean tumor size, number of months between SRS courses, use of WBRT, or use of surgery and the development of RN. Median survival after the second course of SRS was 8.3 months, and median survival for those with and without RN was 14.1 and 7.7 months, respectively (p=0.23). CONCLUSION: Reirradiation with SRS can lead to tumor response in the majority of patients with a low incidence of RN.

Patterns of failure and predictors of outcome in cutaneous malignant melanoma of the scalp.

BACKGROUND: Patients with melanoma of the scalp may have higher failure (recurrence) rates than melanoma of other body sites. OBJECTIVE: We sought to characterize survival and patterns of failure for patients with scalp melanoma. METHODS: Between 1998 and 2010, 250 nonmetastatic patients underwent wide local excision of a primary scalp melanoma. Kaplan-Meier analyses were performed to evaluate overall survival, scalp control, regional neck control, distant metastases-free survival, and disease-free survival. RESULTS: Five-year overall survival was 86%, 57%, and 45% for stages I, II, and III, respectively, and 5-year scalp control rates were 92%, 75%, and 63%, respectively. Five-year distant metastases-free survival for these stages were 92%, 65%, and 45%, respectively. Of the 74 patients who recurred, the site of first recurrence included distant disease in 47%, although 31% recurred in the scalp alone. LIMITATIONS: This is a retrospective review. CONCLUSION: Distant metastases-free survival and overall survival for stage II and III patients with scalp melanoma are poor, and stage III patients experience relatively high rates of scalp failure suggesting that these patients may benefit from additional adjuvant systemic and local therapy. Further research is needed to characterize the environmental, microenvironmental, and genetic causes of the increased aggressiveness of scalp melanoma and to identify more effective treatment and surveillance methods.

An integrin-targeted, pan-isoform, phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo.

PURPOSE: Multiple reports point to an important role for the phosphoinositide-3 kinase (PI3K) and AKT signaling pathways in tumor survival and chemoresistance in multiple myeloma (MM). The goals of our study were: (1) to generate the preclinical results necessary to justify a Phase I clinical trial of SF1126 in hematopoietic malignancies including MM and (2) to begin combining pan-PI3K inhibitors with other agents to augment antitumor activity of this class of agent in preparation for combination therapy in Phase I/II trials. METHODS: We determined the in vitro activity of SF1126 with 16 human MM cell lines. In vivo tumor growth suppression was determined with human myeloma (MM.1R) xenografts in athymic mice. In addition, we provide evidence that SF1126 has pharmacodynamic activity in the treatment of patients with MM. RESULTS: SF1126 was cytotoxic to all tested MM lines, and potency was augmented by the addition of bortezomib. SF1126 affected MM.1R cell line signaling in vitro, inhibiting phospho-AKT, phospho-ERK, and the hypoxic stabilization of HIF1α. Tumor growth was 94 % inhibited, with a marked decrease in both cellular proliferation (PCNA immunostaining) and angiogenesis (tumor microvessel density via CD31 immunostaining). Our clinical results demonstrate pharmacodynamic knockdown of p-AKT in primary patient-derived MM tumor cells in vivo. CONCLUSIONS: Our results establish three important points: (1) SF1126, a pan-PI3K inhibitor has potent antitumor activity against MM in vitro and in vivo, (2) SF1126 displays augmented antimyeloma activity when combined with proteasome inhibitor, bortezomib/Velcade(®), and (3) SF1126 blocks the IGF-1-induced activation of AKT in primary MM tumor cells isolated from SF1126-treated patients The results support the ongoing early Phase I clinical trial in MM and suggest a future Phase I trial in combination with bortezomib in hematopoietic malignancies.

Radiation Dose Escalation in Stage III Non-Small-Cell Lung Cancer.

For patients with stage III non-small-cell lung cancer with unresectable or inoperable tumors, definitive chemoradiotherapy is often utilized. Historically, local control and overall survival rates have been poor. In an effort to improve local control, new chemotherapeutic agents in combination with higher doses of radiotherapy have been investigated. Early dose escalation trials date back to the 1980s, and the feasibility and efficacy of dose escalation for patients with inoperable stage III lung cancer continue to be topics of investigation. Herein, we review the evolution of chemotherapy as it relates to treatment of unresectable stage III lung cancer, and we outline the early and the more recent dose escalation studies. While dose escalation appears to provide a modest benefit in terms of preventing local failure and improving overall survival, advances in diagnostic imaging and radiotherapy treatment have possibly resulted in selection of a more favorable patient population. These variables make statements regarding the benefit of dose escalation challenging.

A surveillance, epidemiology, and end results registry analysis of prostate cancer modality time trends by age.

OBJECTIVE: To use the Surveillance, Epidemiology, and End Results (SEER) registry to analyze age-specific time trends in the use of radiotherapy (RT) (external beam radiotherapy [EBRT], brachytherapy [brachy], and combination therapy [combo]) as first-line treatment for prostate cancer. METHODS: A total of 820,649 prostate cancer patients in the SEER public-use registry (1973-2004) with diagnosis year, treatment, and age information available were identified. Modality use time-trend curves were plotted for patients 45 to 85+ years of age, grouped in 5-year intervals. A nonparametric (Spearman) test was used to assess the correlation between diagnosis year and (a) percentage use of RT and (b) relative percentage use of EBRT, brachy, and combo therapy. RESULTS: Over the study period from 1973 to 2004, RT use increased in patients ≥65 years of age, but has remained stable in patients <65 years of age. All age groups experienced a similar relative rise in the use of brachy and combo therapy, with brachy use surpassing combo use in approximately year 2000. CONCLUSIONS: Trends in treatment choice for early prostate cancer generally reflect treatment advances, but do not appear to be uniform among all age groups. The SEER database is a valuable asset for analyzing these trends and can be used to investigate age-specific treatment patterns.