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Radiation Therapy for Rectal Cancer: Executive Summary of an ASTRO Clinical Practice Guideline

Wo, Jennifer Y; Anker, Christopher J; Ashman, Jonathan B; Bhadkamkar, Nishin A; Bradfield, Lisa; Chang, Daniel T; Dorth, Jennifer; Garcia-Aguilar, Julio; Goff, David; Jacqmin, Dustin; Kelly, Patrick; Newman, Neil B; Olsen, Jeffrey; Raldow, Ann C; Ruiz-Garcia, Erika; Stitzenberg, Karyn B; Thomas, Charles R; Wu, Q Jackie; Das, Prajnan
PURPOSE/OBJECTIVE:This guideline reviews the evidence and provides recommendations for the indications and appropriate technique and dose of neoadjuvant radiation therapy (RT) in the treatment of localized rectal cancer. METHODS:The American Society for Radiation Oncology convened a task force to address 4 key questions focused on the use of RT in preoperative management of operable rectal cancer. These questions included the indications for neoadjuvant RT, identification of appropriate neoadjuvant regimens, indications for consideration of a nonoperative or local excision approach after chemoradiation, and appropriate treatment volumes and techniques. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS:Neoadjuvant RT is recommended for patients with stage II-III rectal cancer, with either conventional fractionation with concurrent 5-FU or capecitabine or short-course RT. RT should be performed preoperatively rather than postoperatively. Omission of preoperative RT is conditionally recommended in selected patients with lower risk of locoregional recurrence. Addition of chemotherapy before or after chemoradiation or after short-course RT is conditionally recommended. Nonoperative management is conditionally recommended if a clinical complete response is achieved after neoadjuvant treatment in selected patients. Inclusion of the rectum and mesorectal, presacral, internal iliac, and obturator nodes in the clinical treatment volume is recommended. In addition, inclusion of external iliac nodes is conditionally recommended in patients with tumors invading an anterior organ or structure, and inclusion of inguinal and external iliac nodes is conditionally recommended in patients with tumors involving the anal canal. CONCLUSIONS:Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for rectal cancer. Future studies will look to further personalize treatment recommendations to optimize treatment outcomes and quality of life.
PMID: 33097436
ISSN: 1879-8519
CID: 4675832

Best Practices for Evaluation and Treatment of Agitated Children and Adolescents (BETA) in the Emergency Department: Consensus Statement of the American Association for Emergency Psychiatry

Gerson, Ruth; Malas, Nasuh; Feuer, Vera; Prasad, Raghuram; Mroczkowski, Megan M; De Pena-Nowak, Maria; Gaveras, Georgia; Goepfert, Eric; Hartselle, Stephanie; Henderson, Schuyler W; Jhonsa, Anik; Kelly, Patrick; Mangini, Lynn; Maxwell, Benjamin; Prager, Laura; Silver, Gabrielle H
Introduction/UNASSIGNED:Agitation in children and adolescents in the emergency department (ED) can be dangerous and distressing for patients, family and staff. We present consensus guidelines for management of agitation among pediatric patients in the ED, including non-pharmacologic methods and the use of immediate and as-needed medications. Methods/UNASSIGNED:Using the Delphi method of consensus, a workgroup comprised of 17 experts in emergency child and adolescent psychiatry and psychopharmacology from the the American Association for Emergency Psychiatry and the American Academy of Child and Adolescent Psychiatry Emergency Child Psychiatry Committee sought to create consensus guidelines for the management of acute agitation in children and adolescents in the ED. Results/UNASSIGNED:Consensus found that there should be a multimodal approach to managing agitation in the ED, and that etiology of agitation should drive choice of treatment. We describe general and specific recommendations for medication use. Conclusion/UNASSIGNED:These guidelines describing child and adolescent psychiatry expert consensus for the management of agitation in the ED may be of use to pediatricians and emergency physicians who are without immediate access to psychiatry consultation.
PMCID:6404720
PMID: 30881565
ISSN: 1936-9018
CID: 3795682

From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins

Verdes, Aida; Anand, Prachi; Gorson, Juliette; Jannetti, Stephen; Kelly, Patrick; Leffler, Abba; Simpson, Danny; Ramrattan, Girish; Holford, Mande
Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics methodologies, including genomics, transcriptomics, and proteomics; (3) chemical and recombinant synthesis of promising peptide toxins; (4) structural characterization through experimental and computational methods; (5) determination of teretoxin bioactivity and molecular function through biological assays and computational modeling; (6) optimization of peptide toxin affinity and selectivity to molecular target; and (7) development of strategies for effective delivery of venom peptide therapeutics. While our research focuses on terebrids, the venomics approach outlined here can be applied to the discovery and characterization of peptide toxins from any venomous taxa.
PMCID:4848642
PMID: 27104567
ISSN: 2072-6651
CID: 2080202

Metformin use and improved response to therapy in rectal cancer

Skinner, Heath D; Crane, Christopher H; Garrett, Christopher R; Eng, Cathy; Chang, George J; Skibber, John M; Rodriguez-Bigas, Miguel A; Kelly, Patrick; Sandulache, Vlad C; Delclos, Marc E; Krishnan, Sunil; Das, Prajnan
Locally advanced rectal cancer is commonly treated with chemoradiation prior to total mesorectal excision (TME). Studies suggest that metformin may be an effective chemopreventive agent in this disease as well as a possible adjunct to current therapy. In this study, we examined the effect of metformin use on pathologic complete response (pCR) rates and outcomes in rectal cancer. The charts of 482 patients with locally advanced rectal adenocarcinoma treated from 1996 to 2009 with chemoradiation and TME were reviewed. Median radiation dose was 50.4 Gy (range 19.8-63). Nearly, all patients were treated with concurrent 5-fluorouracil-based chemotherapy (98%) followed by adjuvant chemotherapy (81.3%). Patients were categorized as nondiabetic (422), diabetic not taking metformin (40), or diabetic taking metformin (20). No significant differences between groups were found in clinical tumor classification, nodal classification, tumor distance from the anal verge or circumferential extent, pretreatment carcinoembryonic antigen level, or pathologic differentiation. pCR rates were 16.6% for nondiabetics, 7.5% for diabetics not using metformin, and 35% for diabetics taking metformin, with metformin users having significantly higher pCR rates than either nondiabetics (P = 0.03) or diabetics not using metformin (P = 0.007). Metformin use was significantly associated with pCR rate on univariate (P = 0.05) and multivariate (P = 0.01) analyses. Furthermore, patients taking metformin had significantly increased disease-free (P = 0.013) and overall survival (P = 0.008) compared with other diabetic patients. Metformin use is associated with significantly higher pCR rates as well as improved survival. These promising data warrant further prospective study.
PMCID:3797563
PMID: 24133632
ISSN: 2045-7634
CID: 2192232

Multiple synchronous gliomas of distinctly different grades

Kelly, Patrick J
PMCID:2958317
PMID: 20975963
ISSN: 2152-7806
CID: 114060

Insular gliomas and lenticulostriate artery position RESPONSE [Letter]

Kelly, PJ; Moshel, Y
ISI:000272493300034
ISSN: 0022-3085
CID: 105713

Glioma vascularity correlates with reduced patient survival and increased malignancy

Russell, Stephen M; Elliott, Robert; Forshaw, David; Golfinos, John G; Nelson, Peter K; Kelly, Patrick J
BACKGROUND: The objective of this study was 2-fold: (1) document the presence and degree of vascularity in gliomas of different pathologic grades and (2) determine whether the presence of abnormal vascularity, determined by catheter angiography, correlates with a shortened survival. METHODS: As part of a protocol for radiographic data acquisition that was used in a computer-assisted, stereotactic system, all patients who underwent biopsy or resection of a newly diagnosed glioma between 1994 and 2000 at our institution routinely underwent preoperative catheter angiography. The presence and degree of tumor vascularity were recorded and then correlated with survival and pathologic grade. The confounding effects of age, KPS, adjuvant treatment, and extent of resection on survival were considered. RESULTS: Two hundred thirty-one patients were included in this study. The mean follow-up of survivors was 7.8 years. Tumor vascularity correlated with a shortened survival (proportional hazards RR for survival, 0.69; 95% CI, 0.58-0.82). This correlation persisted after correction for age, KPS score, adjuvant therapy, and extent of resection (RR, 0.81; 95% CI, 0.68-0.97). Abnormal vascularity was present in 25 (30%) of 82 low-grade (WHO grade 2) gliomas. Overall, the extent of vascularity (none [120 patients, 52%], blush [63 patients, 27%], neovessels [25 patients, 11%], and arteriovenous shunting [23 patients, 10%]) correlated with worse WHO tumor grade (P < .0001). CONCLUSIONS: The presence of abnormal vascularity correlates with both a shortened survival and higher grade of malignancy. These findings underscore the importance of antiangiogenesis factor investigation and drug development for the treatment of gliomas, regardless of their pathologic grade
PMID: 19329156
ISSN: 1879-3339
CID: 101316

Occipital transtentorial approach to the precentral cerebellar fissure and posterior incisural space

Moshel, Yaron A; Parker, Erik C; Kelly, Patrick J
OBJECTIVE: To describe the surgical techniques and postoperative clinical outcomes with the occipital transtentorial (OT) approach in patients harboring lesions arising from the precentral cerebellar fissure, posterior incisural space, and adjoining structures. METHODS: Twenty-two patients underwent microsurgical resection of intra-axial lesions arising within the precentral cerebellar fissure and posterior incisural space between 1997 and 2006. Patient demographics, presenting symptoms, pathology, and neurological outcomes were retrospectively reviewed. Pre- and postoperative magnetic resonance imaging scans were evaluated to determine the anatomic extensions of the lesion and the degree of surgical resection. Patients with lesions primarily confined to the pineal and posterior third ventricle approached by a supracerebellar infratentorial trajectory were excluded from this study. RESULTS: Of the 22 patients reported in this series, 17 (77%) had contrast-enhancing lesions, and 5 (23%) had nonenhancing lesions arising from the precentral cerebellar fissure and posterior incisural space. The lesions were oriented dorsomedial to the midbrain and diencephalon in 6 patients (27%), dorsolateral in 14 patients (64%), and lateral in 2 patients (9%). A lateral OT approach directed under the occipitotemporal junction was used in 16 patients (73%), and an interhemispheric OT approach was used in 6 patients (27%). Transient visual field loss occurred in 3 patients (14%); it resolved by the third follow-up month. Gross total resection or near-total resection of the imaging-defined lesion volume was achieved in 19 patients (86%). CONCLUSION: The OT approaches provide excellent exposure for lesions of the precentral cerebellar fissure, posterior incisural space, and adjacent structures. The lateral OT approach directed under the occipitotemporal junction provides an inline view for lesions situated posterolateral to the brainstem. It also provides an inferiorly directed view under the venous system into the precentral cerebellar fissure and fourth ventricular roof. Visual field deficits are minimized by directing the trajectory under the occipitotemporal junction instead of retracting along the interhemispheric corridor. The interhemispheric OT approach was primarily used for lesions extending superiorly, in the midline or near midline, above the tentorium and venous system into the splenium of corpus callosum, lateral ventricle, and posterior thalamus, where extensive lateral retraction was not required
PMID: 19687701
ISSN: 1524-4040
CID: 101648

Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival

Narayana, Ashwatha; Kelly, Patrick; Golfinos, John; Parker, Erik; Johnson, Glyn; Knopp, Edmond; Zagzag, David; Fischer, Ingeborg; Raza, Shahzad; Medabalmi, Praveen; Eagan, Patricia; Gruber, Michael L
Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1-19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1-7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3-7.7) and 9 (95% CI 7.6-10.4) months, respectively, as calculated from the initiation of the bevacizumab-based therapy. Radiologically demonstrated responses following therapy were noted in 73.6% of cases. Neither the choice of chemotherapeutic agent nor the performance of a resection prior to therapy had an impact on patient survival. Although the predominant pattern of relapse was local, 15 patients (30%) had diffuse disease. Conclusions Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored
PMID: 18834263
ISSN: 0022-3085
CID: 90721

Resection of insular gliomas: the importance of lenticulostriate artery position

Moshel, Yaron A; Marcus, Joshua D S; Parker, Erik C; Kelly, Patrick J
OBJECT: The object of this study was to identify characteristic preoperative angiographic and MR imaging features of safely resectable insular gliomas and describe the surgical techniques and postoperative clinical outcomes. METHODS: Thirty-eight patients with insular gliomas underwent transsylvian resection between 1995 and 2007. Patient demographics, presenting symptoms, pathological findings, and neurological outcomes were retrospectively reviewed. Preoperative MR imaging-defined tumor volumes were superimposed onto the preoperative stereotactic cerebral angiograms to determine whether the insular tumor was confined lateral to (Group I) or extended medially around (Group II) the lenticulostriate arteries (LSAs). RESULTS: Twenty-five patients (66%) had tumors situated lateral to the LSAs and 13 (34%) had tumors encasing the LSAs. Insular gliomas situated lateral to the LSAs led to significant medial displacement of these vessels (161 +/- 39%). In 20 (80%) of these 25 cases the boundaries between tumor and brain parenchyma were well demarcated on preoperative T2-weighted MR images. In contrast, there was less displacement of the LSAs (130 +/- 14%) in patients with insular gliomas extending around the LSAs on angiography. In 11 (85%) of these 13 cases, the tumor boundaries were diffuse on T2-weighted MR images. Postoperative hemiparesis or worsening of a preexisting hemiparesis, secondary to LSA compromise, occurred in 5 patients, all of whom had tumor volumes that extended medial to the LSAs. Gross-total or near-total resection was achieved more frequently in cases in which the insular glioma remained lateral to the LSAs (84 vs 54%). CONCLUSIONS: Insular gliomas with an MR imaging-defined tumor volume located lateral to the LSAs on stereotactic angiography displace the LSAs medially by expanding the insula, have well-demarcated tumor boundaries on MR images, and can be completely resected with minimal neurological morbidity. In contrast, insular tumors that appear to surround the LSAs do not displace these vessels medially, are poorly demarcated from normal brain parenchyma on MR images, and are associated with higher rates of neurological morbidity if aggressive resection is pursued. Preoperative identification of these anatomical growth patterns can be of value in planning resection
PMID: 18976071
ISSN: 0022-3085
CID: 93383