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.

Effect of prophylactic cranial irradiation on survival in elderly patients with limited-stage small cell lung cancer.

BACKGROUND: Prophylactic cranial irradiation (PCI) improves survival in patients with limited-stage small cell lung cancer (SCLC) who have a complete response to chemotherapy and radiotherapy, yet to the best of the authors' knowledge, data specific to the elderly population are lacking. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, the authors identified 1926 patients aged ≥ 70 years who were diagnosed with limited-stage SCLC between 1988 and 1997. Overall survival (OS) for patients who received PCI versus those who did not were estimated using the Kaplan-Meier method and compared with the log-rank test. A Cox proportional hazards model was further fitted to estimate the effect of PCI on OS after adjusting for age, race, sex, tumor size, lymph node status, stage of disease, and receipt of thoracic radiotherapy and surgery. RESULTS: The median age of the patients was 75 years (range, 70 years-94 years) and 138 patients (7.2 %) received PCI. The 2-year and 5-year OS rates were 33.3% (95% confidence interval [95% CI], 25.6%-41.2%) and 11.6% (95% CI, 6.9%-17.6%), respectively, among patients who received PCI versus 23.1% (95% CI, 21.2%-25.1%) and 8.6% (95% CI, 7.3%-9.9%), respectively, among patients who did not receive PCI (P = .028). On multivariable analysis, PCI was found to be an independent predictor of OS (hazards ratio, 0.72; 95% CI, 0.54-0.97 [P = .032]). On subgroup analysis, PCI remained an independent predictor of OS among patients aged ≥ 75 years, but not among patients aged ≥ 80 years. CONCLUSIONS: The receipt of PCI is associated with improved OS in patients aged ≥ 70 years with SCLC, suggesting that the benefit of PCI is maintained in the elderly population.

Therapeutic options for a rising PSA after radical prostatectomy.

INTRODUCTION: Radical prostatectomy is an effective primary treatment for clinically localized prostate cancer. While many patients are cured of their disease after surgery, there are still a significant proportion of men who will develop a biochemical recurrence (BCR). In this review, we detail existing treatment algorithms for this group of patients as well as future therapies that show great promise. MATERIALS AND METHODS: A review of the literature was performed, and relevant, high-impact articles were identified and reviewed focusing on the treatment of men with BCR after surgery for prostate cancer. Wherever possible, we used data from randomized, controlled trials. When lacking, multi-institutional retrospective studies were utilized. RESULTS: In a man with BCR, it is important to differentiate between local and distant failure to help guide treatment decision-making. In many of these men, adjuvant or salvage radiotherapy can improve local control, and in the case of salvage radiotherapy, it can improve overall survival (OS). Moreover, there are several systemic therapies available to men with gross metastases and/or castration resistant prostate cancer (CRPC) that have demonstrated a significant survival advantage as well as symptom control. CONCLUSIONS: In the setting of BCR, many treatment options exist. Each modality has an effective role in the management of men with locally recurrent or metastatic prostate cancer. Furthermore, there are currently a number of effective therapies for men who progress to metastatic CRPC. In this review, we present current data detailing the role/efficacy of each therapy for a rising prostate-specific antigen (PSA) after definitive surgical therapy.

Salvage therapy for locally recurrent prostate cancer after radiation.

INTRODUCTION: External beam radiotherapy (EBRT) is widely utilized as primary therapy for clinically localized prostate cancer. For patients who develop locally recurrent disease after EBRT, local salvage therapy may be indicated. The primary modalities for local salvage treatment in this setting include radical prostatectomy, cryotherapy, and brachytherapy. To date, there is little data describing outcomes and toxicity associated with each of these salvage modalities. MATERIALS AND METHODS: A review of the literature was performed to identify studies of local salvage therapy for patients who had failed primary EBRT for localized prostate cancer. We focused on prospective trials and multi-institutional retrospective series in order to identify the highest level of evidence describing these therapies. RESULTS: The majority of reports describing the use of local salvage treatment for recurrent prostate cancer after EBRT are single-institution, retrospective reports, although small prospective studies are available for salvage cryotherapy and salvage brachytherapy. Clinical outcomes and toxicity for each modality vary widely across studies, which is likely due to the heterogeneity of patient populations, treatment techniques, and definitions of failure. In general, most studies demonstrate that local salvage therapy after EBRT may provide long-term local control in appropriately selected patients, although toxicity is often significant. CONCLUSIONS: As there are no randomized trials comparing salvage treatment modalities for localized prostate cancer recurrence after EBRT, the selection of a local treatment modality should be made on a patient-by-patient basis, with careful consideration of each patient's disease characteristics and tolerance for the risks of treatment. Additional data, ideally from prospective randomized trials, is needed to guide decision making for patients with local recurrence after EBRT failure.

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.

Computed Tomography in Radiation Oncology During the Coronavirus Disease 2019 Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, cancer centers must implement effective measures to protect patients and staff from infection with the novel coronavirus. A critical component of this effort is the timely identification of patients undergoing treatment who have COVID-19. Limitations on testing make such efforts challenging. However, the specialty of radiation oncology is unique in its use of computed tomography (CT) imaging for image guidance, and these CT studies have the potential to identify patients with COVID-19 even before they develop symptoms. Several organizations have developed published guidelines for radiologists to identify characteristic findings of COVID-19 on thoracic CT scans. The present article describes these recommendations in order to educate radiation oncologists on how to identify potential cases of COVID-19 and empower physicians in our field to optimally protect patients and staff.

Functionalization of zeolite ZSM-5 by hydrosilylation and acetone coupling: synthesis, MAS NMR, and theory.

We report a two-step postsynthetic functionalization reaction of zeolite HZSM-5 that proceeds with high selectivity at room temperature. In the first step the framework acid sites of the zeolite are reacted with phenylsilane to replace the acidic proton with a hydrosilyl (-SiH3) group covalently linked to the framework. This group readily couples to acetone in a second step to form a framework-bound hydrosilyl isopropyl ether that is thermally stable at 473 K, but decomposes in the presence of moisture. We characterized these reactions using 29Si, 1H, and 13C MAS NMR, as appropriate. Theoretical modeling using density functional theory and cluster models of the zeolite acid site confirmed that both steps were exothermic and provided theoretical chemical shift values in excellent agreement with experiment.

Impact of neck failure on survival in older patients with differentiated thyroid cancer.

BACKGROUND: Regional recurrence of differentiated thyroid cancer (DTC) is often salvaged with neck dissection without survival penalty. It is unknown whether recurrence may be associated with inferior survival in older patients. METHODS: Surveillance, Epidemiology, and End Results (SEER) and Medicare data were linked to identify patients age ≥65 with nonmetastatic DTC. Patients undergoing neck dissection >6 months after their initial diagnosis were considered to have regional recurrent disease. We compared overall survival (OS) and cause-specific survival (CSS) for patients with recurrent disease versus a matched cohort of patients with non-recurrent DTC. RESULTS: Of 6235 patients, 143 had treatment-defined recurrent disease. Patients with recurrent disease had inferior OS (p < .01) and CSS (p < .01). Multivariate analysis demonstrated that recurrent disease was independently associated with inferior 10-year OS (hazard ratio [HR] = 1.75; p < .01) and CSS (HR = 3.05; p < .01). CONCLUSION: Regional recurrence of DTC may negatively impact OS and CSS in patients ≥65 years old. © 2016 Wiley Periodicals, Inc. Head Neck 38: 919-924, 2016.

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.

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.

Prostate CT segmentation method based on nonrigid registration in ultrasound-guided CT-based HDR prostate brachytherapy.

PURPOSE: The technological advances in real-time ultrasound image guidance for high-dose-rate (HDR) prostate brachytherapy have placed this treatment modality at the forefront of innovation in cancer radiotherapy. Prostate HDR treatment often involves placing the HDR catheters (needles) into the prostate gland under the transrectal ultrasound (TRUS) guidance, then generating a radiation treatment plan based on CT prostate images, and subsequently delivering high dose of radiation through these catheters. The main challenge for this HDR procedure is to accurately segment the prostate volume in the CT images for the radiation treatment planning. In this study, the authors propose a novel approach that integrates the prostate volume from 3D TRUS images into the treatment planning CT images to provide an accurate prostate delineation for prostate HDR treatment. METHODS: The authors' approach requires acquisition of 3D TRUS prostate images in the operating room right after the HDR catheters are inserted, which takes 1-3 min. These TRUS images are used to create prostate contours. The HDR catheters are reconstructed from the intraoperative TRUS and postoperative CT images, and subsequently used as landmarks for the TRUS-CT image fusion. After TRUS-CT fusion, the TRUS-based prostate volume is deformed to the CT images for treatment planning. This method was first validated with a prostate-phantom study. In addition, a pilot study of ten patients undergoing HDR prostate brachytherapy was conducted to test its clinical feasibility. The accuracy of their approach was assessed through the locations of three implanted fiducial (gold) markers, as well as T2-weighted MR prostate images of patients. RESULTS: For the phantom study, the target registration error (TRE) of gold-markers was 0.41 ± 0.11 mm. For the ten patients, the TRE of gold markers was 1.18 ± 0.26 mm; the prostate volume difference between the authors' approach and the MRI-based volume was 7.28% ± 0.86%, and the prostate volume Dice overlap coefficient was 91.89% ± 1.19%. CONCLUSIONS: The authors have developed a novel approach to improve prostate contour utilizing intraoperative TRUS-based prostate volume in the CT-based prostate HDR treatment planning, demonstrated its clinical feasibility, and validated its accuracy with MRIs. The proposed segmentation method would improve prostate delineations, enable accurate dose planning and treatment delivery, and potentially enhance the treatment outcome of prostate HDR brachytherapy.

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.

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 patient's 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.

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.

Application of metabolic PET imaging in radiation oncology.

Positron emission tomography (PET) is a noninvasive imaging technique that provides functional or metabolic assessment of normal tissue or disease conditions and is playing an increasing role in cancer radiotherapy planning. (18)F-Fluorodeoxyglucose PET imaging (FDG-PET) is widely used in the clinic for tumor imaging due to increased glucose metabolism in most types of tumors; its role in radiotherapy management of various cancers is reviewed. In addition, other metabolic PET imaging agents at various stages of preclinical and clinical development are reviewed. These agents include radiolabeled amino acids such as methionine for detecting increased protein synthesis, radiolabeled choline for detecting increased membrane lipid synthesis, and radiolabeled acetate for detecting increased cytoplasmic lipid synthesis. The amino acid analogs choline and acetate are often more specific to tumor cells than FDG, so they may play an important role in differentiating cancers from benign conditions and in the diagnosis of cancers with either low FDG uptake or high background FDG uptake. PET imaging with FDG and other metabolic PET imaging agents is playing an increasing role in complementary radiotherapy planning.

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.