David M. Marcus

Rising Incidence of Mucosal Melanoma of the Head and Neck in the United States

Background. While it is established that the incidence of cutaneous melanoma has risen over time in the United States, the incidence trend for mucosal melanoma of the head and neck (MMHN) is unknown. Methods. We used the Surveillance, Epidemiology, and End Results (SEER) database to determine incidence trends for MMHN from 1987 to 2009 in the United States. We determined annual percent change (APC) by weighted least squares and joinpoint regression analysis. Results. MMHN incidence increased from 1987 to 2009 (APC 2.4%; P < 0.01). Nasal cavity lesions increased in incidence (APC 2.7%; P < 0.01) over this duration, while the incidence of non-nasal cavity lesions remained stable. The highest rate of increase was in white females ages 55 to 84 (APC 5.1%; P = 0.01). Conclusions. The incidence of MMHN in the United States has been rising since 1987. This trend is driven primarily by increased incidence of nasal cavity melanomas.

Prognostic factors for overall survival after radiosurgery for brain metastases from melanoma.

Objectives:Brain metastases (BM) cause significant morbidity and mortality in patients with melanoma. We aimed to identify prognostic factors for overall survival (OS) in patients undergoing stereotactic radiosurgery (SRS) for BM from melanoma. Methods:We identified 135 patients treated with SRS at Emory University between 1998 and 2010 for BM from melanoma. We recorded patient age, number and size of all BM, Karnofsky Performance Status (KPS), presence of extracranial metastases, serum lactate dehydrogenase (LDH), use of whole-brain radiation therapy (WBRT), use of temozolomide, and surgical resection of BM. We used the Kaplan-Meier method to calculate OS, and we compared time-to-event data with the log-rank test. We performed Cox multivariate analysis to identify factors independently associated with OS. Results:Median OS for all patients was 6.9 months. Patients with KPS≥90, 70 to 80, and <70 had median OS of 10.4, 6.1, and 4.5 months, respectively (P=0.02). Patients with LDH<240 had median OS of 7.8 months versus 3.5 months for LDH≥240 (P=0.01). Patients receiving WBRT had median OS of 7.3 months versus 6.5 months for patients not receiving WBRT (P=0.05). KPS and LDH (but not WBRT) were significantly associated with OS on multivariate analysis. Conclusions:In addition to previously identified prognostic factors for OS in patients with BM from melanoma, serum LDH is independently associated with OS. If this finding is confirmed in a prospective manner, the serum LDH level should be included in future prognostic algorithms for patients with melanoma and BM who are to receive SRS.

The impact of multiparametric pelvic magnetic resonance imaging on risk stratification in patients with localized prostate cancer.

OBJECTIVE To determine the impact of multiparametric magnetic resonance imaging (MP-MRI) of the prostate on established risk stratification criteria in patients with clinically localized adenocarcinoma of the prostate (ACP). METHODS The cohort included 71 patients who underwent MP-MRI of the prostate at a tertiary care referral center as part of their initial workup for ACP. Tumor characteristics comprising traditional risk stratification criteria (prostate-specific antigen, clinical T stage, and biopsy Gleason score) were recorded, and the initial National Comprehensive Cancer Network risk group was calculated. The National Comprehensive Cancer Network risk group was then recalculated incorporating MRI findings. The impact of MRI findings on changes in risk group classification was evaluated using the Stuart-Maxwell test. For patients undergoing radical prostatectomy, MRI findings were correlated with pathologic findings. RESULTS The cohort included 11 (15.5%), 39 (54.9%), and 21 patients (29.6%) with low-, intermediate-, and high-risk disease, respectively. MRI findings led to risk group upstaging in 12 cases (16.9%). The highest yield was demonstrated in patients with intermediate-risk disease, in whom MRI led to upstaging in 25.6% of patients. There was a significant difference between pre-MRI and post-MRI risk group classifications (P<.01) for the entire cohort. Compared with radical prostatectomy specimens, the specificity of MRI for T3 disease was 92.9%. CONCLUSION In our cohort of patients undergoing MP-MRI for previously untreated, clinically localized ACP, MRI findings led to changes in risk stratification in a substantial proportion of patients. Our findings support the use of MP-MRI in the workup of patients with localized ACP.

Multiatlas segmentation of thoracic and abdominal anatomy with level set-based local search

Segmentation of organs at risk (OARs) remains one of the most time‐consuming tasks in radiotherapy treatment planning. Atlas‐based segmentation methods using single templates have emerged as a practical approach to automate the process for brain or head and neck anatomy, but pose significant challenges in regions where large interpatient variations are present. We show that significant changes are needed to autosegment thoracic and abdominal datasets by combining multi‐atlas deformable registration with a level set‐based local search. Segmentation is hierarchical, with a first stage detecting bulk organ location, and a second step adapting the segmentation to fine details present in the patient scan. The first stage is based on warping multiple presegmented templates to the new patient anatomy using a multimodality deformable registration algorithm able to cope with changes in scanning conditions and artifacts. These segmentations are compacted in a probabilistic map of organ shape using the STAPLE algorithm. Final segmentation is obtained by adjusting the probability map for each organ type, using customized combinations of delineation filters exploiting prior knowledge of organ characteristics. Validation is performed by comparing automated and manual segmentation using the Dice coefficient, measured at an average of 0.971 for the aorta, 0.869 for the trachea, 0.958 for the lungs, 0.788 for the heart, 0.912 for the liver, 0.884 for the kidneys, 0.888 for the vertebrae, 0.863 for the spleen, and 0.740 for the spinal cord. Accurate atlas segmentation for abdominal and thoracic regions can be achieved with the usage of a multi‐atlas and perstructure refinement strategy. To improve clinical workflow and efficiency, the algorithm was embedded in a software service, applying the algorithm automatically on acquired scans without any user interaction. PACS numbers: 87.57.nm, 87.57.N‐, 87.57.Q‐

A review of low-dose-rate prostate brachytherapy--techniques and outcomes.

Prostate cancer is the most common male cancer in the United States and the second leading cause of male cancer death. The main therapeutic modalities for the treatment of prostate cancer are surgery, external beam radiation therapy, hormonal therapy, and brachytherapy. In recent years, brachytherapy has been increasingly utilized for the treatment of early-stage prostate cancer. Technological advances, including improvements in imaging, planning, and postimplant quality assessment by dosimetry have led to widespread use of brachytherapy. Outcomes for prostate brachytherapy have been shown to be equivalent, in selected patients, to those of other treatment modalities for prostate cancer, including radical prostatectomy and external beam radiation therapy. Further, prostate brachytherapy has quality-of-life benefits in comparison to these other treatment modalities, particularly in the domain of sexual function. This paper describes the history of low-dose rate brachytherapy; current techniques for brachytherapy implantation and postoperative dosimetric evaluation; recent outcomes studies; recent quality-of-life analyses; and current and future prostate brachytherapy developments, including open clinical trials. As research in prostate brachytherapy continues, it is likely that this modality will play an increasingly important role in the treatment of early-stage prostate cancer patients in the future.

Perfluoroctyl bromide as a blood pool contrast agent for computed tomographic angiography.

RATIONALE AND OBJECTIVES We determined whether perfluoroctyl bromide (perflubron) could be used as a computed tomography (CT) angiographic agent by studying vessel visibility (celiac artery, superior mesenteric artery [SMA], and renal arteries) with spiral CT and three-dimensional (3D) reconstructions. METHODS Five rhesus monkeys were examined with a perflubron emulsion (90% [w/v] perfluorochemical; administered intravenously at a dose of 1.5 ml/kg and at a rate of 0.5 ml/sec. Spiral CT was performed immediately and at 5 hr after injection. Three dimensional images of the aorta at the level of the celiac artery, SMA, and renal arteries were reconstructed and blindly rated 0-4 (0 = not seen; 4 = excellent visualization) by two observers. RESULTS All the vessels had the best ratings immediately after injection: celiac artery, 2.8 +/- 0.42; SMA, 2.7 +/- 0.48; left renal artery, 2.1 +/- 0.99; and right renal artery, 1.2 +/- 1.03. The ratings after the 5-hr delay were as follows: celiac artery, 1.3 +/- 1.34; SMA, 1.5 +/- 1.08; left renal artery, 1.5 +/- 0.97; and right renal artery, 1.2 +/- 0.79. CONCLUSIONS Spiral CT angiography with a perflubron emulsion successfully demonstrated all vessels immediately and at 5 hr after contrast agent infusion. Further refinements of the dose, rate, and reconstruction technique are expected to increase vessel visibility over this wide imaging window.

Outcomes and prognostic factors in modern era management of major salivary gland cancer

OBJECTIVES There is a dearth of prospective evidence regarding cancer of the major salivary glands. Outcomes and management of major salivary gland are based largely on retrospective series spanning many decades and changes in surgical, radiation, imaging and systemic therapy strategies and technique. We sought to report contemporary patterns of relapse and prognostic factors for major salivary gland cancer. MATERIALS AND METHODS 112 patients with major salivary gland cancers underwent resection with or without adjuvant therapy between January 1997 and September 2010. Outcomes were documented with follow-up until December 2014. Survival was calculated by the Kaplan-Meier method. Log-rank test and Cox proportional hazards regression were performed with locoregional control (LRC), distant control (DC) and overall survival (OS) as the primary outcome variables. RESULTS Median follow-up was 55.1 months. Rates of LRC for stage I/II and III/IV at five years were 95.7% and 61.9% respectively. Rates of DC at five years for stage I/II and III/IV were 93% and 56.9% respectively. Multivariate analysis identified larger tumor size, clinical nerve involvement and in parotid cancers, advanced T stage, no adjuvant radiation, and older age at diagnosis to be associated with increased risk of locoregional recurrence (all p<0.05). Distant metastasis was associated with sublingual site, degree of clinical nerve involvement, high grade, tumor size and in parotid tumors additionally deep lobe involvement on multivariate analysis (all p<0.05). CONCLUSION Several prognostic factors were identified that may help guide decisions regarding adjuvant therapy. DM remains a significant concern in the management of this disease.

Reduced acute toxicity associated with the use of volumetric modulated arc therapy for the treatment of adenocarcinoma of the prostate.

PURPOSE Novel techniques to deliver intensity modulated radiation therapy (IMRT) have resulted in improved treatment efficiency and dosimetric endpoints. We aimed to compare acute gastrointestinal (GI) and genitourinary (GU) toxicity in patients treated for adenocarcinoma of the prostate (ACP) using volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS A total of 122 (71 IMRT and 51 VMAT) ACP patients treated from 2004 to 2011 with definitive external beam radiation therapy were analyzed. Dose-volume histogram endpoints (V40, V65, V70, and V75 of the bladder and rectum) were collected for each patient. Median follow-up for patients treated with VMAT was 269 days versus IMRT was 1121 days. Acute Common Toxicity Criteria for Adverse Events (CTCAE) GI and GU toxicity scores, obtained during each weekly treatment check, were compared across cohorts. The univariate (UV) association between the covariates and outcomes was assessed and multivariable (MV) cumulative logit models were fit for each outcome. RESULTS Median patient age was 68 years and median prostate-specific antigen was 8.3. Both bladder and rectal V40, V65, V70, and V75 were all higher in the IMRT group versus the VMAT group (P < .05), which was likely influenced by larger planning target volumes in the IMRT group. The VMAT group had significantly lower rates of acute GU and acute GI CTCAE toxicity on UV association analysis. On MV analysis, VMAT remained independently associated with acute GU (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.07-0.44; P < .001) and GI (OR, 0.16; 95% CI, 0.07-0.41; P < .001) toxicity. CONCLUSIONS VMAT appears to be independently associated with lower rates of acute GI and GU toxicity when compared with traditional IMRT. Further exploration of toxicity improvements associated with VMAT use in the definitive treatment of ACP is needed.

Small cell carcinoma of the anus in the setting of prior squamous dysplasia and carcinoma in situ

Small cell carcinoma of the anus is a rare tumor that has been infrequently described in the literature. In contrast to squamous cell carcinoma, which is known to be associated with high-risk subtypes of human papillomavirus (HPV), the etiology of small cell carcinoma of the anal canal is not established. We present a case of a patient with small cell carcinoma of the anal canal in the setting of prior squamous dysplasia and carcinoma in situ. In conjunction with recently published data demonstrating the presence of HPV in tumor specimens from patients with small cell carcinoma of the anal canal, our patients clinical course suggests a possible link between HPV and this rare malignancy.

Neoadjuvant hormonal therapy is associated with comparable outcomes to neoadjuvant chemotherapy in post-menopausal women with estrogen receptor-positive breast cancer

Objectives: We compared outcomes in post-menopausal estrogen receptor-positive (ER+) breast cancer patients treated with neoadjuvant hormonal therapy (NAHT) or neoadjuvant chemotherapy (NACT). Methods: We retrospectively identified post-menopausal women who received either NAHT or NACT for non-metastatic, non-inflammatory, ER+, Her2neu negative breast cancer from 2004 to 2011. We compared long-term rates of locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS), and overall survival (OS) using the Kaplan–Meier method. The Cox proportional hazards model was used to identify patient and disease factors significantly associated with these endpoints. Results: We identified 99 patients in our study, including 27 who received NAHT and 72 who received NACT. There were no differences in 4-year LRFS, DMFS, or OS between groups. On Cox proportional hazards modeling, the type of systemic therapy (NAHT versus NACT) was not associated with OS. However, patients with progesterone receptor (PR) positive disease had a 92% lower risk of death compared to patients with PR negative disease. Conclusion: Our data suggest that outcomes are not adversely affected by NAHT in post-menopausal women with ER+ breast cancer. Therefore, NAHT is a viable and potentially less toxic option than NACT in appropriately selected patients. Furthermore, although PR negative disease appears to be associated with poor prognosis, intensification of systemic treatment with chemotherapy may not be associated with improvement of disease-related outcomes in this patient population.