bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoplasms of the Adrenal Cortex
Authors: Fojo Tito 
Published: March 2017

Overview
Adrenocortical cancer (ACC) is a rare malignancy, with varied presentations and a poor prognosis. Imaging studies have emerged as central to a work up, and in most cases a biopsy is not needed and should not be performed. Pathologic examination is very valuable with the Weiss criteria used to discriminate a small adenomas from carcinomas. Management is multidisciplinary and includes surgical resection or ablation, oral mitotane, intravenous chemotherapy, and palliative radiation. Surgery remains the only proven curative option, must be considered at presentation, and relapse with laparoscopic resection avoided. Mitotane is approved for the treatment of inoperable functional and nonfunctional ACC and its clinical value is primarily as an anti‐hormonal agent. In a patient whose tumor is producing an excess of hormones mitotane is indispensable, however, its use in the adjuvant setting is uncertain. Replacement steroids are needed. Systemic chemotherapy using mitotane in combination with etoposide, doxorubicin, and cisplatin (EDP‐M) or with streptozotocin (S‐M) are the preferred options. These should not be discarded in favor of a “novel targeted therapy”, none of which have shown any proven efficacy. Increasing evidence suggests that palliative radiation therapy is beneficial for patients with metastatic disease. Radiofrequency ablation (RFA) or cryoablation have emerged as surgical adjuncts or stand‐alone modalities for recurrences. As with most rare diseases, enrollment in clinical trials is strongly encouraged.
Tumors of the Diffuse Neuroendocrine and Gastroenteropancreatic System
Authors: Vosburgh Evan 
Published: March 2017

OverviewThe diffuse neuroendocrine system (DES) is represented by a small number of cells spread through the body, and the tumors that derive from these cells present a wide spectrum of epidemiologic, pathologic, biologic, genetic, and clinical features. Clinical and scientific investigation of the inherited multiple endocrine neoplasia (e.g., MEN‐1, MEN‐2) syndromes, and the various unique clinical syndromes secondary to secretion of specific peptides (e.g., insulinomas, glucagonomas, VIPomas) are challenging. Clinical presentation can be dramatic, nonspecific, or incidentally noted in absence of symptoms. Tumors might be small, difficult to detect tumors (<1 cm in size) or bulky hepatic metastases in a well patient. Cancer registry data show five‐year survivals for tumors of the neuroendocrine system that have not improved in the past several decades, and that remain about 30–60%. The same registry data documents a rising and unexplained incidence of these tumors, particularly the neuroendocrine tumors of the gastroenteropancreatic system (GEP‐NETs), that when coupled with the long average survival results in prevalence figures similar to cancers such as testicular, ovarian, and multiple myeloma.Recent advances in understanding of the genetics, biology, clinical features, and response to therapy are better defining subtypes of neuroendocrine tumors once clustered and studied as “carcinoids.” Revised histologic grouping and staging are informing ongoing clinical trials and are providing more informed clinical care of these diverse tumors. Recent approvals of several targeted therapies with progression‐free survival benefit suggest that the status quo is changing for tumors of the DES.
Neoplasms of the Head and Neck
Authors: Ferrarotto Renata , Kies Merrill S. , Garden Adam S. , Kupferman Michael E. 
Published: March 2017

OverviewHead and neck cancers (HNCs) comprise a diverse group of malignancies affecting the upper aerodigestive tract. The most common tumor type is squamous cell carcinoma. While the main risk factors for HNC remain tobacco and alcohol abuse, oncogenic viruses such as human papilloma virus and Epstein–Barr virus play a major carcinogenic role in tumors of the oropharynx and nasopharynx, respectively. The management of head and neck malignancies is site and histology specific, and requires a multidisciplinary team approach. In this chapter, we review the current knowledge of HNC, with focus on squamous and salivary cancers, and discuss ongoing and future research aiming to improve the management and outcomes of patients with these malignancies.
Thymomas and Thymic Tumors
Authors: Kelly Ronan J. , Marchevsky Alberto M. 
Published: March 2017

OverviewThymomas, carcinomas, and other thymic neoplasms are rare and comprise fewer than 1.5% of all solid tumors. They are currently classified according to the recently updated (2015) histologic classification of the World Health Organization (WHO). The histologic features and classification criteria for thymomas and thymic carcinomas are reviewed in this chapter, with an emphasis on various diagnostic problems. Thymomas are staged according to the Masaoka–Koga system, although the American Joint Commission on Cancer (AJCC) is currently developing staging guidelines. There is some current uncertainty regarding how to stage thymic carcinomas. Thymoma patients with stages I and II are treated with radical thymectomy, whereas radiation therapy and chemotherapy are used in patients with more advanced stages. This chapter discusses in detail the current state of the art for the treatment of thymomas and other thymic neoplasms. The results of various therapeutic options are difficult to evaluate with certainty in the absence of a significant number of randomized clinical trials. Indeed, level I and II evidence is difficult to gather for patients with neoplasms that are rare, have a long natural history, and require follow‐up for many years. The efforts of the International Thymic Malignancies Interest Group (ITMIG) to develop evidence‐based guidelines for the diagnosis, staging, and treatment of thymic neoplasms are described.
Tumors of the Heart and Great Vessels
Authors: Yu Anthony F. , Yeung Sai‐Ching Jim , Escalante Carmen P. , van der Zee Sarina , Chahinian A. P. , Fuster Valentin 
Published: March 2017

OverviewPrimary tumors of the heart and great vessels are rare, but secondary tumors are significantly more common. Clinical manifestations of cardiac tumors depend on the location and size of the mass, not on the histopathology of the tumor. Several noninvasive imaging modalities including echocardiography, cardiac MRI, cardiac CT, and PET are currently available to provide complementary information on the location, extent, and tissue characteristics of a cardiac tumor. The clinical management of patients with cardiac tumors varies based on the type of tumor, clinical symptoms, and overall prognosis.
Primary Germ Cell Tumors of the Thorax
Authors: Hainsworth John D. , Greco F. Anthony 
Published: March 2017

OverviewPrimary germ cell tumors (GCT) of the thorax are rare but potentially curable. Benign teratomas account for approximately 60–70% and usually appear in young adults. The large majority of these tumors are curable with surgical excision. Malignant mediastinal GCT usually occur in young men and can be divided histologically into pure seminoma (∼52% of cases) and various nonseminoma histologies. Pure seminomas are highly sensitive to chemotherapy; treatment with three cycles of bleomycin, etoposide, and cisplatin (BEP) as used in testicular cancer is curative in more than 80%. Selected patients with small (<6 cm) localized seminomas have high cure rates with radiation therapy alone. Nonseminomatous mediastinal GCT are associated with Klinefelter's syndrome (5–10% of cases) and are also associated with various acute leukemias. Optimal treatment includes four cycles of BEP chemotherapy (or an equivalent regimen), followed by resection of residual mediastinal masses. The cure rate for these relatively poor prognosis GCT is approximately 45%.
Testis Cancer
Authors: Kollmannsberger Christian , Nichols Craig R. , Daneshmand Siamak , Hansen Eric K. , Corless Christopher L. , Roth Bruce J. , Einhorn Lawrence 
Published: March 2017

OverviewCancer of the testis is a relatively uncommon disease, accounting for approximately 1% of all cancers in males. However, it represents a highly curable neoplasm, the incidence of which is focused on young patients at their peak of productivity. Curative treatment of disseminated nonseminomatous germ cell tumors often combines surgery and chemotherapy. The goal of initial therapy is never palliation or prolongation of survival, but cure.
Neoplasms of the Vulva and Vagina
Authors: Dewdney Summer B. , Rotmensch Jacob 
Published: March 2017

Overview
Vulvar and vaginal carcinomas are uncommon diseases that generally affect post‐menopausal women, although 19% of vulvar carcinomas occur in women >50 years old. Risk factors for vulvar cancer include human papilloma virus and chronic inflammation. Vulvar intraepithelial neoplasia can often be managed with wide local excision, but several other modalities have been utilized. Most vulvar malignancies are squamous cell carcinomas that are managed by surgical excision and radiotherapy. Sentinel lymph node biopsy has been used to spare the morbidity observed after regional lymph node dissection. For more advanced lesions, chemo‐radiotherapy with agents such as 5‐FU, cisplatin, and mitomycin C is utilized. Other vulvar malignancies include Bartholin gland carcinomas, basal cell carcinomas, verrucous carcinomas, and melanomas. Carcinomas of the vagina are most frequently squamous cell, but clear cell adenocarcinomas have been seen in younger women. In the past, clear cell carcinomas were associated with prenatal exposure to diethyl‐stibestrol. Vaginal melanomas can occur, as well as endodermal sinus tumors, rhrabdomysarcomas, and fibroepithelial vagina polyps.
Endometrial Cancer
Authors: Rahaman Jamal , Lu Karen , Cohen Carmel J. 
Published: March 2017

Overview
Endometrial carcinoma is the most frequent gynecologic cancer in the United States with over 50,000 new cases diagnosed per year. Over 80% have Type I cancers with the classic estrogen‐dependent endometrioid histology and a favorable prognosis. Type II cancers have a different molecular profile associated with more virulent disease and diminished survival and include uterine serous papillary carcinomas (UPSC) and clear cell carcinomas. The Cancer Genome Atlas (TCGA) has recently defined four molecular subtypes of endometrial cancer based on somatic mutations, copy number alterations, and microsatellite instability status. Over 75% of patients are present with irregular or postmenopausal bleeding. Surgical staging includes a total hysterectomy, bilateral salpingo‐oophorectomy, and pelvic and para‐aortic lymph node sampling, which can be performed via a laparotomy, laparoscopy, or robotic surgery. Surgery, where possible, constitutes the definitive primary treatment for most patients with endometrial carcinoma. Primary radiation therapy and primary hormonal therapy are alternatives for inoperable patients. Adjuvant therapy for Stage I disease is determined by age, depth of myometrial invasion, lymphovascular space invasion, and tumor grade. For patients with advanced and recurrent disease, radiation therapy, chemotherapy, and hormonal therapy are utilized. Paclitaxel (T), carboplatin (C), cisplatin (P), and doxorubicin (A) are the most active single agents with TC and TAP being the most effective combination of chemotherapy regimens. Hormonal therapy includes oral progestins, the progesterone‐containing intrauterine device, tamoxifen, gonadotropin‐releasing hormone analogs, and aromatase inhibitors. Emerging biologic agents with activity include bevacizumab and mTOR inhibitors. Tumor molecular profiling, minimal invasive surgery, sentinel lymph node assessment, and integration of novel biologic therapies will likely play a greater role in the future.
Coagulopathic Complications of Cancer Patients
Authors: De Sancho Maria T. , Rand Jacob H. 
Published: March 2017

OverviewBleeding and thrombotic complications are common in cancer patients. The bleeding complications usually result from abnormalities in platelets or deficiency of coagulation factors and require specific blood or coagulation factor replacement. Thromboembolic events including deep venous thrombosis and pulmonary embolism are common and associated with serious complications. New biomarkers, diagnostic imaging approached and anticoagulant therapies have significantly improved the care of these patients. Ongoing research in the understanding of the various disturbances in hemostasis, application of innovative treatment modalities, and use of appropriate thromboprophylaxis in cancer patients should lead to further decreased morbidity and improved survival.
Cardiac Complications
Authors: Ewer Michael S. , Ewer Steven M. , Suter Thomas 
Published: March 2017

OverviewPatients with malignant diseases often have coexisting cardiovascular disorders or may face serious cardiovascular complications in the course of their disease. The disorders may result from underlying conditions such as atherosclerosis, hypertension, or valvular abnormalities, or they may result directly from cancer or its treatment (Table 1). In addition, cardiovascular disorders that are unusual in patients not afflicted with cancer may be more common in the cancer patient and sometimes are unsuspected. Furthermore, cardiovascular diseases common in the general population must not be overlooked in patients with cancer; the presentation of such entities may be unusual, and the diagnosis often is more complex. Increased clinical scrutiny is therefore necessary in this vulnerable population. Multiple clinical problems may also coexist and defy a simple illumination because of the complex interactions between the malignancy, its treatment, and the cardiovascular system; what affects one often alters the presentation and course of the others. This chapter will look at some of the more common cardiovascular complications of cancer and its treatment, and will also address some of the dilemmas encountered in cancer patients with concomitant cardiac conditions.
Oral Complications of Cancer and Their Treatment
Authors: Sonis Stephen T. , Yuan Anna 
Published: March 2017

OverviewThe mouth is a frequent site of direct and indirect adverse side effects of cancer therapy. In myelosuppressed patients, its diverse microbiota makes the oral cavity both a site of local infection and a potential source of bacteremias and sepsis. While about half of all patients being treated with chemotherapy or radiation therapy will develop some form of oral toxicity or infection, almost every patient receiving an aggressive myeloablative regimen or local radiotherapy to the head and neck manifests acute and chronic toxicities. The diversity of the tissues found in and around the mouth—keratinized and nonkeratinized mucosa, bone, salivary glands, and teeth—contributes to the range of susceptibility, acuity, and clinical implications of regimen‐related oral complications. In almost all instances, precancer treatment elimination or control of existing oral diseases and aggressive management of oral health during cancer therapy favorably impacts outcomes.
Lung volume reproducibility under ABC control and self‐sustained breath‐holding
Authors: Kaza Evangelia , Dunlop Alex , Panek Rafal , Collins David J. , Orton Matthew , Symonds‐Tayler Richard , McQuaid Dualta , Scurr Erica , Hansen Vibeke , Leach Martin O. 
Published: March 2017

AbstractAn Active Breathing Coordinator (ABC) can be employed to induce breath‐holds during CT imaging and radiotherapy of lung, breast and liver cancer, and recently during lung cancer MRI. The apparatus measures and controls respiratory volume, hence subject lung volume reproducibility is its principal measure of effectiveness. To assess ABC control quality, the intra‐session reproducibility of ABC‐induced lung volumes was evaluated and compared with that reached by applying the clinical standard of operator‐guided self‐sustained breath‐holds on healthy volunteers during MRI. Inter‐session reproducibility was investigated by repeating ABC‐controlled breath‐holds on a second visit. Additionally, lung volume agreement with ABC devices used with different imaging modalities in the same institution (MR, CT), or for a breast trial treatment, was assessed. Lung volumes were derived from three‐dimensional (3D) T1‐weighted MRI datasets by three observers employing semiautomatic lung delineation on a radiotherapy treatment planning system. Inter‐observer variability was less than 6% of the delineated lung volumes. Lung volume agreement between the different conditions over all subjects was investigated using descriptive statistics. The ABC equipment dedicated for MR application exhibited good intra‐session and inter‐session lung volume reproducibility (1.8% and 3% lung volume variability on average, respectively). MR‐assessed lung volumes were similar using different ABC equipment dedicated to MR, CT, or breast radiotherapy. Overall, lung volumes controlled by the same or different ABC devices agreed better than with self‐controlled breath‐holds, as suggested by the average ABC variation of 1.8% of the measured lung volumes (99 mL), compared to the 4.1% (226 mL) variability observed on average with self‐sustained breath‐holding.
Comparison of CT images with average intensity projection, free breathing, and mid‐ventilation for dose calculation in lung cancer
Authors: Khamfongkhruea Chirasak , Thongsawad Sangutid , Tannanonta Chirapha , Chamchod Sasikarn 
Published: March 2017

AbstractThe purpose of this study was to compare three computed tomography (CT) images under different conditions—average intensity projection (AIP), free breathing (FB), mid‐ventilation (MidV)—used for radiotherapy contouring and planning in lung cancer patients. Two image sets derived from four‐dimensional CT (4DCT) acquisition (AIP and MidV) and three‐dimensional CT with FB were generated and used to plan for 29 lung cancer patients. Organs at risk (OARs) were delineated for each image. AIP images were calculated with 3D conformal radiotherapy (3DCRT) and intensity‐modulated radiation therapy (IMRT). Planning with the same target coverage was applied to the FB and MidV image sets. Plans with small and large tumors were compared regarding OAR volumes, geometrical center differences in OARs, and dosimetric indices. A gamma index analysis was also performed to compare dose distributions. There were no significant differences (P > 0.05) in OAR volumes, the geometrical center differences, maximum and mean doses of the OARs between both tumor sizes. For 3DCRT, the gamma analysis results indicated an acceptable dose distribution agreement of 95% with 2%/2 mm criteria. Although, the gamma index results show distinct contrast of dose distribution outside the planning target volume (PTV) in IMRT, but within the PTV, it was acceptable. All three images could be used for OAR delineation and dose calculation in lung cancer. AIP image sets seemed to be suitable for dose calculation while patient movement between series acquisition of FB images should be considered when defining target volumes on 4DCT images.
Photon Optimizer (PO) prevails over Progressive Resolution Optimizer (PRO) for VMAT planning with or without knowledge‐based solution
Authors: Jiang Fan , Wu Hao , Yue Haizhen , Jia Fei , Zhang Yibao 
Published: March 2017

AbstractThe enhanced dosimetric performance of knowledge‐based volumetric modulated arc therapy (VMAT) planning might be jointly contributed by the patient‐specific optimization objectives, as estimated by the RapidPlan model, and by the potentially improved Photon Optimizer (PO) algorithm than the previous Progressive Resolution Optimizer (PRO) engine. As PO is mandatory for RapidPlan estimation but optional for conventional manual planning, appreciating the two optimizers may provide practical guidelines for the algorithm selection because knowledge‐based planning may not replace the current method completely in a short run. Using a previously validated dose–volume histogram (DVH) estimation model which can produce clinically acceptable plans automatically for rectal cancer patients without interactive manual adjustment, this study reoptimized 30 historically approved plans (referred as clinical plans that were created manually with PRO) with RapidPlan solution (PO plans). Then the PRO algorithm was utilized to optimize the plans again using the same dose–volume constraints as PO plans, where the line objectives were converted as a series of point objectives automatically (PRO plans). On the basis of comparable target dose coverage, the combined applications of new objectives and PO algorithm have significantly reduced the organs‐at‐risk (OAR) exposure by 23.49–32.72% than the clinical plans. These discrepancies have been largely preserved after substituting PRO for PO, indicating the dosimetric improvements were mostly attributable to the refined objectives. Therefore, Eclipse users of earlier versions may instantly benefit from adopting the model‐generated objectives from other RapidPlan‐equipped centers, even with PRO algorithm. However, the additional contribution made by the PO relative to PRO accounted for 1.54–3.74%, suggesting PO should be selected with priority whenever available, with or without RapidPlan solution as a purchasable package. Significantly increased monitor units were associated with the model‐generated objectives but independent from the optimizers, indicating higher modulation in these plans. As a summary, PO prevails over PRO algorithm for VMAT planning with or without knowledge‐based technique.
Metal‐Free, TBHP‐Mediated, [3+2+1]‐Type Intermolecular Cycloaddition Reaction: Synthesis of Pyrimidines from Amidines, Ketones, and DMF through C(sp3)−H Activation
Authors: Zheng Lv‐Yin , Guo Wei , Fan Xiao‐Lin 
Published: March 2017

AbstractAn efficient method for the direct construction of pyrimidines from a metal‐free, TBHP‐mediated, [3+2+1]‐type intermolecular cycloaddition reaction from amidines, ketones, and DMF through C(sp3)−H activation has been developed. This transformation involves the formation of new C−C/C−N bonds and features sustainable oxidants, readily available starting materials, and high atom and step economies.
Equatorial Ligand Perturbations Influence the Reactivity of Manganese(IV)‐Oxo Complexes
Authors: Massie Allyssa A. , Denler Melissa C. , Cardoso Luísa Thiara , Walker Ashlie N. , Hossain M. Kamal , Day Victor W. , Nordlander Ebbe , Jackson Timothy A. 
Published: March 2017

AbstractManganese(IV)‐oxo complexes are often invoked as intermediates in Mn‐catalyzed C−H bond activation reactions. While many synthetic MnIV‐oxo species are mild oxidants, other members of this class can attack strong C−H bonds. The basis for these reactivity differences is not well understood. Here we describe a series of MnIV‐oxo complexes with N5 pentadentate ligands that modulate the equatorial ligand field of the MnIV center, as assessed by electronic absorption, electron paramagnetic resonance, and Mn K‐edge X‐ray absorption methods. Kinetic experiments show dramatic rate variations in hydrogen‐atom and oxygen‐atom transfer reactions, with faster rates corresponding to weaker equatorial ligand fields. For these MnIV‐oxo complexes, the rate enhancements are correlated with both 1) the energy of a low‐lying 4E excited state, which has been postulated to be involved in a two‐state reactivity model, and 2) the MnIII/IV reduction potentials.