bluuebunny/crossref_metadata_2025 huggingface dataset:
Rheumatic manifestations of acromegaly
Authors: Panevin Taras S. , Alekseeva Lyudmila I. , Melnichenko Galina A.
Published: February 2020

Acromegaly is a chronic endocrine disease characterized by excessive secretion of growth hormone (GH), which, in turn, leads to increased insulin-like growth factor 1 (IGF-1) secretion by the liver. GH and IGF-1 excess leads to excessive cell and tissue growth, including the osteoarticular apparatus. Joint pain in acromegaly is a frequent and early symptom. In some cases, joint manifestations can be one of the first signs of acromegaly and their intensity increases with duration of the active disease. Estimated prevalence of joint damage signs is around 70% of patients at the time of diagnosis of acromegaly. Musculoskeletal system alterations can manifest either in axial skeleton and peripheral joints. Besides arthropathy, patients with acromegaly (both active and controlled) are more prone to vertebral fractures, although it was previously thought that acromegaly has a low risk of osteoporosis. In this article, we review features of damage to the axial skeleton, peripheral joints in the setting of excessive GH and IGF-1 production, as well as the association of autoimmune rheumatic diseases and acromegaly.
Trastuzumab Emtansine (T-DM1): Hitching a Ride on a Therapeutic Antibody
Authors: Burris Howard A.
Published: February 2020

Overview:

The treatment of cancers with chemotherapy is frequently limited by side effects. The effectiveness may be improved by the use of monoclonal antibodies to deliver cytotoxic agents to cancer cells while limiting exposure to normal tissues. The use of antibody-drug conjugates (ADCs) is one such strategy: a drug connected by a linker to an antibody specific for a tumor antigen is the basic makeup of an ADC. Overexpression and amplification of HER2 is associated with clinically aggressive breast cancers, and the use of trastuzumab to target HER2 has been highly effective. That said, most patients with HER2-positive metastatic breast cancer will eventually have disease progression during targeted therapy. Trastuzumab emtansine (T–DM1) is a novel ADC that combines the humanized antibody trastuzumab and the potent antimicrotubule agent T-DM1 (derivative of maytansine) using a unique and highly stable linker. The potential of maytansine was found in the 1970s with clinical responses noted against breast cancer; however, substantial toxicity prohibited further development. DM1 possesses in vitro cytotoxicity 10 to 200 times greater than that of taxanes and vinca alkaloids. A phase I trial of T-DM1 for patients with heavily pretreated HER2-positive breast cancer determined a recommended dose of 3.6 mg per kilogram delivered every 3 weeks. Responses were seen in multiple patients. T-DM1 was then studied in phase II trials of patients with HER2-positive metastatic breast cancer. In a studies of 112 and 110 patients in whom disease had progressed during HER2-directed therapy, T-DM1 was associated with objective response rates of 26% and 34%, respectively. The agent was well tolerated in both trials, with most toxicities being grade 1 and 2, and no bleeding episodes or cardiac events occurring. Additional phase II and III trials are now evaluating T-DM1 in the first-line setting. In one such trial, T-DM1 was compared with standard dosing of trastuzumab every 3 weeks plus docetaxel every 3 weeks. Objective response rates were comparable and grade 3 or4 adverse events were substantially reduced in the T-DM1 arm. The anticipated selective activity and reduction in side effects were thus noted. Randomized multicenter phase III trials are ongoing, including the EMILIA trial, an open-label trial of T-DM1 compared with the U.S. Food & Drug Administration-approved regimen of capecitabine plus lapatinib. The results of studies completed to date suggest T-DM1 is active in patients who have cancer resistant to trastuzumab-based combinations.
The Future of Oncology Care with Personal Health Records
Authors: Feldman Henry , Rodriguez Elizabeth S.
Published: February 2020

Overview:

Personal health records (PHRs) and patients' access to their own clinical information through a patient portal are changing the patient-physician relationship. Historically, health care providers have been gatekeepers of patients' medical records. Now, these portals provide patients access to clinical information, electronic messaging with the clinical team, and appointment and billing information. This type of access supports patient empowerment by engaging patients in their own care. Patients desire online access to information. The health care industry, like any other, must respond to the needs of its consumers. Oncology practices face unique challenges to meeting this need because of the complex nature of medical records of patients with cancer. Health care providers worry about the consequences of patients receiving “bad news” online, thereby increasing patient anxiety. This anxiety may, in turn, increase providers' workload by creating additional calls or visits to the office. These valid concerns require careful consideration when implementing a PHR or patient portal into a practice. Providers will benefit from a clear understanding of actual compared with potential risks and benefits. Much of the concerns about the negative effect on providers' workload and the potential increase in patients' anxiety have not been borne out. On the other hand, the implementation strategy, governance structure, and end-user education are crucial components to ensuring success. Successful implementation of a PHR or patient portal affords the opportunity to improve patient satisfaction and increase efficiency in provider workflow. The possibility exists to improve patient outcomes by engaging the patient in decision making and follow through.
A New Direction for Pancreatic Cancer Treatment: FOLFIRINOX in Context
Authors: Kindler Hedy Lee
Published: February 2020

Overview:

Since 1996, the cornerstone of chemotherapy for advanced pancreatic cancer has been gemcitabine, which has a genuine, but modest effect on survival and quality of life. It has been remarkably difficult to improve on these outcomes. Many phase III studies of gemcitabine doublets have been uniformly negative, with the exception of a trial of gemctabine plus erlotinib, which provided only marginal benefit. In 2010, the FOLFIRINOX regimen (bolus and infusional 5-fluorouracil, irinotecan, and oxaliplatin) emerged as a major treatment advance for patients with metastatic pancreatic cancer. In a trial with 342 patients, FOLFIRINOX yielded a longer median overall survival (11.1 vs. 6.8 months, hazard ratio [HR] 0.57, p < 0.001), a superior progression-free survival (6.4 vs. 3.3 months, HR 0.47, p < 0.001), a higher objective response rate (31.6% vs. 9.4%, p < 0.001), and a significant increase in time until definitive deterioration in quality of life, compared with gemcitabine. FOLFIRINOX is also more cost-effective than gemcitabine. Because of higher rates of grade 3 to 4 neutropenia (46% vs. 21%), febrile neutropenia (5% vs. 1%), and diarrhea (13% vs. 2%) with FOLFIRINOX, vigilant patient selection, education, and monitoring are essential. Retrospective single-institution series confirm the substantial activity of FOLFIRINOX in metastatic, locally advanced, and previously-treated patients; demonstrate its safety in individuals with biliary stents; and elucidate how physicians routinely modify drug doses without clear evidence or guidelines. Ongoing and planned studies will prospectively evaluate FOLFIRINOX in the adjuvant, locally advanced, and borderline resectable settings, will add targeted agents to FOLFIRINOX, and will evaluate how to adjust doses to ameliorate toxicity.
Targeted Therapy in Sarcoma: Should We Be Lumpers or Splitters?
Authors: Riedel Richard F. , Maki Robert G. , Wagner Andrew J.
Published: February 2020

Overview:

The identification of KIT as a critical driver in the pathogenesis of GI stromal tumor (GIST), and its subsequent inhibition with imatinib, have resulted in tremendous efforts to identify other potential therapeutic targets for the heterogeneous group of diseases known as sarcomas. Because of the rarity of sarcoma and the often limited number of patients per individual sarcoma subtype, clinical trials to date have often utilized unselected patient populations including multiple subtypes. Although this strategy increases the ease with which a particular trial may accrue patients, statistically significant therapeutic responses across an unselected patient population are often limited. Furthermore, in the absence of biologic correlatives, the identification of significant activity and subsequent interpretation of clinical trial results utilizing targeted therapies for this patient population have been challenging. However, hints have emerged, on the basis of preclinical and clinical observations, to suggest that certain targeted therapeutic approaches are appropriate in select histologic subtypes. This brief review will highlight data supporting the use of targeted therapy in both unselected and selected sarcoma patient populations.
Adjuvant Treatment of Gastrointestinal Stromal Tumor: The Proof, The Pro, and the Practice
Authors: Verweij Jaap
Published: February 2020

Overview:

Gastrointestinal stromal tumors (GIST) are rare tumors, but they are the most common mesenchymal tumor of the gastrointestinal tract, driven by mutations in KIT and PDGF. The KIT and PDGF inhibiting agent imatinib has been tested as adjuvant postsurgery in GIST patients with an intermediate or high risk of relapse. Two of three prospective, randomized controlled studies have meanwhile been reported. The American College of Surgical Oncology Group (ACOSOG) in 713 patients reported a relapse-free survival benefit for adjuvant imatinib given for 1 year, but not an overall survival benefit. The Scandinavian Sarcoma Group (SSG) performed a study comparing 1 year of imatinib to 3 years of imatinib. At 3 years the overall survival (OS) in patients with 3 years of imatinib therapy was similar to the OS in those with 1 year of imatinib 96% and 94% respectively, while at 5 years these numbers were 92% and 82% (HR: 0.45; 95% CI [0.22–0.89]; p = 0.019). Data from the largest study, conducted by the European Organisation for Research and Treatment of Cancer (EORTC) in 908 patients randomly assigned to receive either 2 years of adjuvant imatinib or no imatinib, have not yet been reported. Based on the current evidence, 3 years of imatinib at a daily dose of 400 mg should be considered in patients with a 50% or higher risk of relapse within 5 years after surgery. The evidence and the remaining caveats are discussed.
Ductal Carcinoma In Situ: Challenges, Opportunities, and Uncharted Waters
Authors: Hoffman Abigail W. , Ibarra-Drendall Catherine , Espina Virginia , Liotta Lance , Seewaldt Victoria
Published: February 2020

Overview:

Ductal carcinoma in situ (DCIS) is a heterogeneous group of diseases that differ in biology and clinical behavior. Until 1980, DCIS represented less than 1% of all breast cancer cases. With the increased utilization of mammography, DCIS now accounts for 15% to 25% of newly diagnosed breast cancer cases in the United States. Although our ability to detect DCIS has radically improved, our understanding of the pathophysiology and factors involved in its progression to invasive carcinoma is still poorly defined. In many patients, DCIS will never progress to invasive breast cancer and these women are overtreated. In contrast, some DCIS cases are clinically aggressive and the women may be undertreated. We are able to define some of the predictors of aggressive DCIS compared with DCIS of low malignant potential. However, our ability to risk-stratify DCIS is still in its infancy. Clinical risk factors that predict aggressive disease and increased risk of local recurrence include young age at diagnosis, large lesion size, high nuclear grade, comedo necrosis, and involved margins. Treatment factors such as wider surgical margins and radiation therapy reduce the risk of local recurrence. DCIS represents a key intermediate in the stepwise progression to malignancy, but not all aggressive breast cancers appear to have a DCIS intermediate, notably within triple-negative breast cancer. Ongoing studies of the genetic and epigenetic alterations in precancerous breast lesions (atypia and DCIS) as well as the breast microenvironment are important for developing effective early detection and individualized targeted prevention.
Research and Standard Care: Lung Cancer in China
Authors: Mok Tony S. , Zhou Qing , Wu Yi-Long
Published: February 2020

Overview:

China has an enormous burden from rising tobacco consumption and lung cancer incidence. Governmental intervention on lung cancer prevention is insufficient, and both incidence and mortality related to lung cancer are still on the rise. Treatment guidelines are available, but heterogeneity in the quality of care between centers, especially the disparity between urban and rural areas, have resulted in inconsistent care to patients with lung cancer. Despite knowledge on molecular-targeted therapy, only a small fraction of patients have access to routine EGFR mutation analysis. Platinum-based doublet chemotherapy remains the most commonly used regimen irrespective of mutation status. On a positive note, both clinical and translational research on lung cancer are in rapid progress. The Chinese Thoracic Oncology Group (CTONG) has already contributed substantially to the care of patients with lung cancer and is expected to continue in the trend.
Future Directions in Glioblastoma Therapy
Authors: Colman Howard
Published: February 2020

Overview:

The standard of care for both newly diagnosed and recurrent glioblastoma (GBM) patients has changed significantly in the past 10 years. Surgery followed by radiation and concurrent and adjuvant temozolomide is now the well-established standard treatment for newly diagnosed GBM. More recently, bevacizumab has become a mainstay of treatment for recurrent GBM. However, despite these advances and significant improvements in patient outcomes, the management and treatment of GBM patients remains a challenging and frustrating endeavor. Difficulties in interpretation of imaging changes after initial treatment, as well as the effects of antiangiogenic agents like bevacizumab on MRI characteristics, can make even the determination of disease progression complicated in multiple situations. Although a high percentage of patients benefit from antiangiogenic therapy in terms of radiographic response and progression-free survival, the effects of bevacizumab on prolonging overall survival remain controversial. Furthermore, tumor progression after treatment with antiangiogenic agents carries a particularly poor prognosis and there is a general lack of effective therapies for this group of patients. These limitations in terms of standard treatments contrast with a relative wealth of new information regarding the molecular underpinnings of GBM. Data from several large-scale efforts to molecularly profile GBM tumors including The Cancer Genome Atlas (TCGA) project have helped define specific molecular subtypes of GBM with distinct biology and clinical outcomes. These findings are helping to refine our understanding of the molecular heterogeneity and pathogenesis of these tumors and provide a basis for the future development of rational and targeted therapies for specific tumor subtypes.
Insights into the Molecular Genetics of Myeloproliferative Neoplasms
Authors: Nguyen Huong (Marie) , Gotlib Jason
Published: February 2020

Overview:

The molecular biology of the BCR-ABL1-negative chronic myeloproliferative neoplasms (MPNs) has witnessed unprecedented advances since the discovery of the acquired JAK2 V617F mutation in 2005. Despite the high prevalence of JAK2 V617F in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), and the common finding of dysregulated JAK-STAT signaling in these disorders, it is now appreciated that MPN pathogenesis can reflect the acquisition of multiple genetic mutations that alter several biologic pathways, including epigenetic control of gene expression. Although certain gene mutations are identified at higher frequencies with disease evolution to the blast phase, MPN initiation and progression are not explained by a single, temporal pattern of clonal changes. A complex interplay between acquired molecular abnormalities and host genetic background, in addition to the type and allelic burden of mutations, contributes to the phenotypic heterogeneity of MPNs. At the population level, an inherited predisposition to developing MPNs is linked to a relatively common JAK2-associated haplotype (referred to as ‘46/1’), but it exhibits a relatively low penetrance. This review details the current state of knowledge of the molecular genetics of the classic MPNs PV, ET, and PMF and discusses the clinical implications of these findings.
Overdiagnosis and Overtreatment of Prostate Cancer
Authors: Thompson Ian M.
Published: February 2020

Overview:

Prostate cancer is a ubiquitous disease, affecting as many as two-thirds of men in their 60s. Through widespread prostate-specific antigen (PSA) testing, increasing rates of prostate biopsy, and increased sampling of the prostate, a larger fraction of low-grade, low-volume tumors have been detected, consistent with tumors often found at autopsy. These tumors have historically been treated in a manner similar to that used for higher-grade tumors but, more recently, it has become evident that with a plan of active surveillance that reserves treatment for only those patients whose tumors show evidence of progression, very high disease-specific survival can be achieved. Unfortunately, the frequency of recommendation of an active surveillance strategy in the United States is low. An alternative strategy to improve prostate cancer detection is through selected biopsy of those men who are at greater risk of harboring high-grade, potentially lethal cancer. This strategy is currently possible through the use of risk assessment tools such as the Prostate Cancer Prevention Trial Risk Calculator ( www.prostate.cancer.risk.calculator.com ) as well as others. These tools can predict with considerable accuracy a man's risk of low-grade and high-grade cancer, allowing informed decision making for the patient with a goal of detection of high-risk disease. Ultimately, other biomarkers including PCA3, TMPRSS2:ERG, and [-2]proPSA will likely aid in discriminating these two types of cancer before biopsy.
Professionalism in Global, Personalized Cancer Care: Restoring Authenticity and Integrity
Authors: Surbone Antonella
Published: February 2020

Personalized medicine is revolutionizing cancer care and creating new expectations among oncologists and patients. At present the benefit is still marginal, however, and must be understood as incremental. In addition, cultural and resource disparities limit the sustainability of new cancer therapies on a global scale. Adequate instruments are needed to enable our exercise of sound and honest judgment in distinguishing breakthrough treatments from those that yield only marginal or doubtful improvements, and to develop strategies for formulation and correct application of balanced guidelines for sustainable cancer care. Professionalism requires that the acquisition of knowledge and skills go hand in hand with moral education in the intellectual virtues of humility, perseverance, adaptability, communicativeness, and commitment to resist self-deception or conflicts of interest. Hidden curricula undermine the moral values of medicine: these must be understood and uncovered. We should possess a special body of knowledge, skills, and values that allow us to change our practices when appropriate and to be stewards of society's limited resources through proper communication with our patients and families. In the era of personalized oncology and global issues of sustainability, professional authenticity and integrity in cancer clinical practice are key to bridging the gaps between true and false expectations of patients and the public.
Approach to the Older Patient with Stage II/III Colorectal Cancer: Who Should Get Curative-Intent Therapy?
Authors: Ramsdale Erika , Sanoff Hanna , Muss Hyman
Published: February 2020

The majority of new colorectal cancer diagnoses occur in adults 65 and older a rapidly growing segment of the U.S. population. Older adults are a markedly heterogeneous group, and although recent clinical trials in locally advanced colorectal cancer have incorporated limited numbers of older patients, the data can not be generalized to most older patients. In particular, patients who are not “fit”—those with poor functional reserve, major comorbidities, or who otherwise meet criteria for frailty or “prefrailty”—are poorly represented in published trials. Population-based data demonstrate that older adults are much less likely to be treated in the adjuvant or neoadjuvant settings for stage II/III colorectal cancer, but it is unclear what the basis should be for withholding potentially curative therapy. Age and Eastern Cooperative Oncology Group (ECOG) performance status (PS) are frequently used to determine eligibility for treatment, but data increasingly suggest these are inadequate; the emerging definition of a spectrum of “fit” to “frail” older patients may provide additional guidance. Available data suggest that fit older patients may benefit as much from curative-intent therapy as younger patients. For frail or vulnerable (prefrail) patients, on the other hand, the benefit must be carefully weighed against the risk of toxicity and competing risks from their comorbidities. Life expectancy and patient preferences should always be elucidated. Geriatrician comanagement may be helpful in determining priorities, providing a comprehensive assessment, and modifying competing risk factors. Even many vulnerable or frail patients can successfully complete (and derive benefit from) carefully considered treatment regimens.
Achieving Health Equity in Colorectal Cancer: A Call to Action
Authors: Cipriano Toni M. , Polite Blase N.
Published: February 2020

Whether defined by race, ethnicity, or socioeconomic status, there are clear health disparities in colon cancer—disparities that exist whether you measure screening, incidence, or mortality. Rather than rehash disparity statistics, the purpose of this educational article is to highlight important resources and how they can be used to help narrow these disparities. Although the logistics can be complex, the general solutions to eliminating colon cancer health disparities are not complex. They are as follows: Asymptomatic persons need to be screened. After being screened, they need to be diagnosed. After being diagnosed, they need to receive appropriate treatment in a timely fashion. After receiving treatment, they have to receive appropriate follow-up and information and advice on lifestyle changes. If we can implement these measures, then cancer-specific mortality disparities will be dramatically reduced, if not eliminated.
Individualizing Treatment Decisions for Older Adults with Hematologic Malignancies
Authors: Klepin Heidi D. , Rizzieri David , Palumbo Antonio , Magarotto Valeria , Eichhorst Barbara
Published: February 2020

Hematologic malignancies are a common cause of morbidity and mortality among older adults, who represent the majority of patients diagnosed with these diseases. Treatment options and disease outcomes have improved in recent years because of the development of novel treatment strategies and the design of elderly-specific clinical trials. Despite this, extrapolation of clinical trial data to patients routinely seen in practice is challenging because of the presence of multimorbidity and functional impairments. Individualized treatment decision making requires not only an understanding of underlying tumor biology but also careful estimation of an older patient's anticipated ability to withstand the stresses of therapy. This article will discuss approaches to standardizing patient assessment strategies and tailoring therapeutic decisions for older adults with hematologic malignancies with a focus on acute myeloid leukemia (AML), allogeneic bone marrow transplantation, multiple myeloma (MM), and chronic lymphocytic leukemia (CLL).
Pathologic Diagnosis, Origin, and Natural History of Pseudomyxoma Peritonei
Authors: Buell-Gutbrod Rebecca , Gwin Katja
Published: February 2020

Mucinous ascites and pools of mucin within the peritoneal cavity associated with neoplastic, mucinous epithelium are the characteristic features of pseudomyxoma peritonei (PMP). Clinically, PMP presents with abdominal distension and gelatinous ascites. In female patients, pelvic masses can be seen. Radiologic findings on computed tomography include scalloping of the hepatic and splenic margins and dense ascites. Surgically, PMP is encountered as grossly visible mucin in the peritoneal cavity. The presence of mucin outside of the appendix, in the right lower quadrant, and beyond is an important diagnostic finding. The appendix may be distended or ruptured. In women, there is often bilateral surface involvement of the ovaries, raising the differential diagnosis of primary ovarian neoplasms; however, these are extremely rare causes of PMP. Because of the association between appendiceal lesions and metastatic mucinous neoplasms of the ovary, appendectomy in the setting of any mucinous peritoneal or ovarian process may be prudent, even if the appendix is grossly normal. The gastrointestinal tract, especially the hepatopancreato biliary system, also needs to be assessed by the surgeon. Pathologically, PMP arises almost exclusively from low- or high-grade mucinous neoplasms of the appendix. These neoplasms must be distinguished both from rare benign causes of mucinous ascites and from nonappendiceal primary tumors. PMP has a protracted clinical course with progressive fibrous adhesions and obstructive disease; aggressive surgical and cytoreductive therapy with hyperthermic intraperitoneal chemotherapy has been reported to improve clinical outcomes.
Locally Advanced Head and Neck Cancer
Authors: Cmelak Anthony J. , Arneson Kyle , Chau Nicole G. , Gilbert Ralph W. , Haddad Robert I.
Published: February 2020

Treatment of locally advanced head and neck squamous cell carcinomas requires a multidisciplinary approach to be able to offer patients definitive therapy while aiming to preserve organ function and minimize acute and long-term toxicities. Advances in surgical techniques will be reviewed for both primary sites and the neck and also in the salvage settings. Recent data on concurrent versus sequential chemoradiotherapy in these patients will be reviewed, with emphasis on identification of appropriate patients for sequential chemoradiotherapy. Finally, advances in modern radiotherapy modalities that have resulted in improved dosimetry and quality of life following treatment will be reviewed.
The Effect of Biology in the Treatment of Small Breast Tumors
Authors: Perez-Garcia Jose , Muñoz-Couselo Eva , Cortes Javier
Published: February 2020

Although the outcome of small (T1a/b) node-negative breast tumors is generally excellent, in the absence of prospective clinical trials, we are limited to data derived from retrospective analyses. Overall, the 10-year overall mortality rate is approximately 20%, while the 10-year breast cancer-specific mortality is in the range of 4% to 8% among this population in the absence of systemic therapy. This clearly reflects that many patients die of causes not related to breast cancer. Due in large part to breast cancer screening programs, the incidence of small tumors is increasing. There is consequently a growing interest in identifying factors that negatively affect the prognosis of these patients. Several studies have shown that patients with triple-negative and HER2+ tumors have a worse prognosis compared with hormone-receptor–positive, HER2- small breast cancers. However, the recent explosion of knowledge of the molecular characteristics of tumors is opening a new way to address cancer. Different genomic assays are currently available to help better predict the outcome of breast cancer patients. However, none of these techniques have been specifically evaluated in patients with small (T1a/b) node-negative tumors, and only a small number of patients with these tumors were included in those studies. In addition, very limited data are available about the role of these assays in patients with triple-negative or HER2-positive cancers. Although a chemotherapy-based strategy might be useful for triple-negative or HER2-positive T1b tumors, more information is urgently needed in order to optimize the treatment of our patients.
Salivary Gland Cancer: An Update on Present and Emerging Therapies
Authors: Carlson Julie , Licitra Lisa , Locati Laura , Raben David , Persson Fredrik , Stenman Göran
Published: February 2020

Malignant salivary gland tumors make up a small proportion of malignancies worldwide, yet vary widely in terms of histology, patterns of spread, and recurrence. A better understanding of this variability will guide appropriate treatment recommendations and lead to improved outcomes. Recent molecular genetic studies have uncovered a translocation-generated gene fusion network in salivary gland carcinomas that can be used for diagnosis, treatment decisions, and development of specific targeted therapies. The gene fusions encode novel fusion oncoproteins that function as transcriptional coactivators, tyrosine kinase receptors, and transcription factors involved in growth-factor signaling and cell-cycle regulation. While surgery currently is the primary therapy for operable tumors, radiation plays an important role in the postoperative setting, as well as in the definitive setting for inoperable lesions. An awareness of the risk factors for tumor recurrence and spread is important for both adjuvant therapy referrals and for radiation treatment planning purposes. Additionally, chemotherapy is being used increasingly in both the concurrent setting as a radiosensitizer, as well as in the palliative setting for metastatic tumors. Future trials investigating concurrent chemotherapy and radiation, as well as the use of targeted agents based on evolving molecular discoveries, will elucidate optimal personalized approaches for this challenging disease.
Disparities and Challenges in Adherence to Oral Antineoplastic Agents
Authors: Accordino Melissa K. , Hershman Dawn L.
Published: February 2020

The issue of medication noncompliance is becoming increasingly important in oncology as more cancer therapies are delivered orally. Medication adherence is difficult to assess and there is no gold standard of measurement. The act of measuring adherence can affect outcomes. Medication noncompliance is common, and is estimated to be 50% in treatment of chronic diseases. Studies have shown that women initiate adjuvant hormonal therapy for breast cancer 64% to 88% of the time when prescribed. Of those who initiate therapy, 50% to 80% are adherent for the prescribed duration, depending on the study. Patients noncompliant with adjuvant hormonal therapy for breast cancer have worse overall survival than their counterparts. Suboptimal treatment responses in chronic myeloid leukemia (CML) are also associated with medication noncompliance. Poor adherence can also affect clinical trial results, leading to inaccuracies of treatment efficacy. Barriers to compliance can occur on the individual, cultural, or system level. Examples of specific barriers are side effects, cost and access to medication, and individual health beliefs. Specific populations, including racial minorities, elderly patients, and very young patients, may be at higher risk for medication noncompliance. Strategies to improve compliance are multifactorial and include improvement of patient education, reduction of treatment side effects, interventions to alter behavior, and changes in public policy to improve financial barriers to treatment. Technology has been an effective tool in improving compliance in noncancer-related illness, and ongoing studies are evaluating its role in the oncology population.
Biology and Treatment of Acute Lymphocytic Leukemia in Adolescents and Young Adults
Authors: Advani Anjali S.
Published: February 2020

The treatment of young adults (16 to 39 years of age) with acute lymphocytic leukemia (ALL) has been a focus of clinical research over the past decade. This review will focus on the biology, optimal treatment, treatment-related toxicities, and psychosocial issues in this patient population.
Overcoming Resistance in Chronic Myelogenous Leukemia
Authors: Mauro Michael J.
Published: February 2020

Resistance in chronic myelogenous leukemia is an issue that has developed in parallel to the availability of rationally designed small molecule tyrosine kinase inhibitors to treat the disease. A significant fraction of patients with clinical resistance are recognized to harbor point mutations/substitutions in the Abl kinase domain, which limit or preclude drug binding and activity. Recent data suggest that compound mutations may develop as well. Proper identification of clinical resistance and prudent screening for all causes of resistance, ranging from adherence to therapy to Abl kinase mutations, is crucial to success with kinase inhibitor therapy. There is currently an array of Abl kinase inhibitors with unique toxicity and activity profiles available, allowing for individualizing therapy beginning with initial choice at diagnosis and as well informed choice of subsequent therapy in the face of toxicity or resistance, with or without Abl kinase domain mutations. Recent studies continue to highlight the merits of increasingly aggressive initial therapy to subvert resistance and importance of early response to identify need for change in therapy. Proper knowledge and navigation amongst novel therapy options and consideration of drug toxicities, individual patient characteristics, disease response, and vigilance for development of resistance are necessary elements of optimized care for the patient with chronic myelogenous leukemia.
Competing Risks in Low-Risk Breast Cancer
Authors: Strasser-Weippl Kathrin , Goss Paul E.
Published: February 2020

In recent years a growing amount of data on prognostic features of breast cancer has allowed for identification of tumors with a very low risk of recurrence. Markers used to predict the risk of distant spread include classic clinicopathologic features as well as newer tumor gene signatures, which have been validated and are being used in cohorts of patients with breast cancer patients who have low-risk disease. However, the definition of “low-risk” breast cancer requires consideration of patient-related factors such as comorbidities and age in addition to tumor characteristics, as high competing risks for mortality might be more important than cancer recurrence from a patient's point of view. In addition, identification of low-risk breast cancer cohorts is only valuable if treatment decisions are based on this information. Therefore, the magnitude of any treatment benefit in low-risk disease needs to be quantified in a comprehensible way. However, treatment benefit in low-risk situations is hard to quantify, may vary over time, and needs to be compared to individual risks for side effects. Decision models considering tumor and patient characteristics as well as predictive markers for treatment efficacy and toxicity will be needed. Tools such as Adjuvant! Online ultimately need to include information from gene signatures in order to reliably recommend specific treatment options for patients with breast cancer patients who have low-risk disease.
Lung Cancer in 2013: State of the Art Therapy for Metastatic Disease
Authors: Shepherd Frances A. , Bunn Paul A. , Paz-Ares Luis
Published: February 2020

Lung cancer is the leading worldwide cause of cancer death and the majority of patients present with metastatic stage IV disease. At diagnosis, clinical, histologic, and molecular features must be considered in therapeutic decision-making for systemic therapy. Molecular testing for at least epidermal growth factor receptor ( EGFR) and ALK should be performed in all patients before therapy. Platinum doublet chemotherapy may be considered for “fit” patients who do not have a molecular driver genetic abnormality. Bevacizumab can be considered for addition to the doublet in patients with nonsquamous cancers who have no contraindications. A pemetrexed combination is considered only in nonsquamous histology. Patients with EGFR mutations or ALK fusions should be treated with erlotinib or crizotinib, respectively, even in patients with tumor-related poor performance. The tyrosine-kinase inhibitors (TKIs) may be continued until multisite, symptomatic progression. For patients initially treated with a platinum doublet, maintenance chemotherapy with pemetrexed, erlotinib, gemcitabine, or possibly docetaxel is an option with selection based on clinical features, histology, type of initial therapy, and response to first-line therapy.
Current State-of-the-Art Therapy for Advanced Squamous Cell Lung Cancer
Authors: Scagliotti Giorgio V. , Novello Silvia , Rapetti Simonetta , Papotti Mauro
Published: February 2020

Squamous cell carcinoma (SCC) represents the second most common histologic subtype of lung cancer (preceded only by adenocarcinoma). SSC of the lung is prevalently diagnosed in smokers and has been described as a preferentially centrally located tumor in which the main airways are commonly involved. Clinically, it presents with predominant locoregional signs and symptoms, but in recent years an increasing frequency of peripheral SCC of the lung has been reported. Pathologic diagnosis can be easily made through light microscopy and immunohistochemistry. The treatment approach for early-stage disease does not differ from that of other histologic subtypes of non–small cell lung cancer; in locally advanced unresectable or metastatic disease, doublet chemotherapy regimens (including cisplatin or carboplatin and a third-generation agent such as gemcitabine, taxanes, or vinorelbine) remain the cornerstone of front-line systemic treatment. Conversely, a single agent, mainly docetaxel, is the preferred treatment in second-line treatment. In unselected patient populations, targeted therapies have been extensively tested in combination with cytotoxic chemotherapy with disappointing results because of increased toxicity or lack of improvement in efficacy outcomes. Genomic alterations in SCC of the lung have not been comprehensively characterized, and no molecularly targeted therapies have been specifically developed for the treatment of this disease, but recently immune checkpoints have emerged as new therapeutic agent.
Tobacco and Lung Cancer: Risks, Trends, and Outcomes in Patients with Cancer
Authors: Warren Graham W. , Cummings K. Michael
Published: February 2020

Tobacco use, primarily associated with cigarette smoking, is the largest preventable cause of cancer mortality, responsible for approximately one-third of all cancer deaths. Approximately 85% of lung cancers result from smoking, with an additional fraction caused by secondhand smoke exposure in nonsmokers. The risk of lung cancer is dose dependent, but can be dramatically reduced with tobacco cessation, especially if the person discontinues smoking early in life. The increase in lung cancer incidence in different countries around in the world parallels changes in cigarette consumption. Lung cancer risks are not reduced by switching to filters or low-tar/low-nicotine cigarettes. In patients with cancer, continued tobacco use after diagnosis is associated with poor therapeutic outcomes including increased treatment-related toxicity, increased risk of second primary cancer, decreased quality of life, and decreased survival. Tobacco cessation in patients with cancer may improve cancer treatment outcomes, but cessation support is often not provided by oncologists. Reducing the health related effects of tobacco requires coordinated efforts to reduce exposure to tobacco, accurately assess tobacco use in clinical settings, and increase access to tobacco cessation support. Lung cancer screening and coordinated international tobacco control efforts offer the promise to dramatically reduce lung cancer mortality in the coming decades.
Developing Novel Strategies to Target B-Cell Malignancies
Authors: Fowler Nathan , Oki Yasuhiro
Published: February 2020

In the past several years we have seen the identification and validation of several key pathways that drive malignant B-cell development. In addition, the effect nonmalignant effector cells within the immune microenvironment have on tumor survival, proliferation, and possibly chemotherapy resistance is increasingly understood. Although there is still much to be learned, this improved understanding combined with rapid advances in medicinal chemistry focusing on structure-based drug design have resulted in a shift in the development of new agents away from traditional chemotherapy to more selective agents targeting key cellular pathways. Examples of “hot” new therapeutic targets include the B-cell receptor signaling pathway, PI3K/mTOR/AKT pathway, histone deacetylases (HDAC), regulators of apoptosis such as the BCL-2 family, the proteasome, and cell–cell interactions within the tumor environment. Many drugs that target specific agents in early clinical development have demonstrated activity in various subtypes of lymphoma and leukemia. Monoclonal and conjugated antibodies targeting cell surface proteins such as CD19, CD22, CD37, and different epitopes of CD20 have also shown promise in relapsed B-cell malignancies and are rapidly moving into efficacy studies. This review will focus on a few of the new nonantibody-based targeted agents in development, their respective pathways, and their activity in various B-cell malignancies.
Surveillance Options for Patients with Uveal Melanoma Following Definitive Management
Authors: Francis Jasmine H. , Patel Sapna P. , Gombos Dan S. , Carvajal Richard D.
Published: February 2020

Even though less than 1% of uveal melanoma patients are found to have radiographic or clinical evidence of distant disease at the time of treatment for their intraocular disease, they carry a lifetime risk of disease recurrence, with approximately 50% of patients ultimately developing fatal metastases. Despite this significant risk, there is no consensus within the ophthalmologic or oncologic community regarding the role of surveillance for detection of metastatic disease in these patients. The lack of consensus is due to the notable absence of clear data regarding the best radiologic or serum surveillance modalities, the optimal frequency of testing, or the ideal length of follow-up. Given the ability to assess prognosis by cytogenetics, gene expression profiling, or other methods, questions remain about whether surveillance strategies should be tailored by level of risk. Importantly, no survival benefit from the early detection of asymptomatic disease in uveal melanoma has been documented, resulting in controversy over the value of routine surveillance and advocacy from some clinicians to forego surveillance altogether. However, there are several factors supporting surveillance: the patient's enhanced emotional well-being, the potential to identify oligometastatic disease amenable to surgery or other local therapies, decreased morbidity/complications from advanced disease, and identification of patients eligible for clinical trials that assess novel therapies for advanced uveal melanoma. The selection of surveillance modality used varies according to local expertise and resources and may include serum markers (liver function tests and others) and/or imaging (chest x-ray, abdominal ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging).
Genomic, Prognostic, and Cell-Signaling Advances in Uveal Melanoma
Authors: Harbour J. William
Published: February 2020

Uveal melanoma (UM) is the second-most common form of melanoma and the most common primary intraocular malignancy. Up to one-half of patients are at risk for fatal metastatic disease. The metastatic potential of an individual tumor can be accurately determined by analysis of a fine-needle aspirate with gene expression profiling assay that is available for routine clinical use through a commercial Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. The test renders one of two results—class 1 (low metastatic risk) or class 2 (high metastatic risk)—and has been extensively validated in multiple centers. Until recently, the genetic mutations and signaling aberrations in UM were largely unknown. With the advent of new genomic sequencing technologies, however, the molecular landscape of UM is rapidly emerging. Mutations in the Gq alpha subunits GNAQ and GNA11 are mutually exclusive and represent early or initiating events that constitutively activate the MAPK pathway. Mutations in BRCA1-associated protein-1 ( BAP1) and splicing factor 3B subunit 1 ( SF3B1) also appear to be largely mutually exclusive, and they occur later in tumor progression. BAP1 mutations are strongly associated with metastasis, whereas SF3B1 mutations are associated with a more favorable outcome. BAP1 mutations can arise in the germ line, leading to a newly described BAP1 familial cancer syndrome. These discoveries have led to new clinical trials to assess several classes of compounds, including MEK, protein kinase C, and histone deacetylase inhibitors, in the adjuvant setting for high-risk patients identified as class 2, as well as in the setting of advanced disseminated disease.
Multidisciplinary Approach to Brain Metastasis from Melanoma: The Emerging Role of Systemic Therapies
Authors: Long Georgina V. , Margolin Kim A.
Published: February 2020

Melanoma brain metastases are common, difficult to treat, and carry a poor prognosis. Until recently, systemic therapy was ineffective. Local therapy (including surgery, stereotactic radiotherapy, and whole brain radiotherapy) was considered the only option for a chance of disease control in the brain, and was highly dependent on the patient's performance status and age, number and size of brain metastases, and the presence of extracranial metastases. Since 2010, three drugs have demonstrated activity in progressing or “active” brain metastases including the anti-CTLA4 antibody ipilimumab (phase II study of 72 patients), and the BRAF inhibitors dabrafenib (phase II study of 172 patients, both previously treated and untreated brain metastases) and vemurafenib (a pilot study of 24 patients with heavily pretreated brain metastases). The challenge and unanswered question for clinicians is how to sequence all the available therapies, both local and systemic, to optimize the patient's quality of life and survival. This is an area of intense clinical research. The treatment of patients with melanoma brain metastases should be discussed by a multidisciplinary team of melanoma experts including a neurosurgeon, medical oncologist, and radiation oncologist. Important clinical features that help determine appropriate first line therapy include single compared with solitary brain metastasis, resectablity, BRAF mutation status of melanoma, rate of progression/performance status, and the presence of extracranial disease.