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Vaccine Therapy, Oncolytic Viruses, and GliomasIn this article, we will discuss some of the vaccination and oncolytic virus strategies being evaluated in the clinic for malignant gliomas. The vaccines reviewed here include the cell-based and the non–cell-based.
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A 54-Year-Old Woman With Recurrent Headaches and SeizuresThe patient’s medical history is remarkable only for asthma and mild emphysema. The family history included a grandmother with gastric cancer. The patient had been taking estrogen replacement therapy since menopause 3 years earlier, and she was
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Tandem Transplantation in Multiple MyelomaThe use of high-dose chemotherapy and autologous stem cellsupport in the past decade has changed the outlook for patients withmultiple myeloma. In newly diagnosed patients, complete remissionrates of 25% to 50% can be achieved, with median disease-free andoverall survivals exceeding 3 and 5 years, respectively. Despite theseresults, autologous transplantation has not changed the ultimatelyfatal outcome of the disease, as there is no substantial evidence of“cure” in most published studies. An additional high-dose chemotherapycourse (with tandem transplants) appears to improve progressionfreesurvival, although the effect is not discernible until 3 to 5 yearsposttransplant. The recent reports of tandem autologous transplant formaximum cytoreduction followed by nonmyeloablative allogeneictransplant for eradication of minimal residual disease appears promisingand deserve further investigation. A central issue of tandemtransplants, whether they involve autologous or allogeneic transplants,revolves around defining the subsets of patients who will benefitfrom the procedure. Good-risk patients (defined by normal cytogeneticsand low beta-2–microglobulin levels), especially those who achievea complete or near-complete response after the first transplant, appearto benefit the most from a second cycle. High-risk patients (defined bychromosomal abnormalities usually involving chromosomes 11 and 13and high beta-2–microglobulin levels) whose median survival aftertandem transplant is less than 2 years should be offered novel therapeuticinterventions such as tandem “auto/allo” transplants. Until theefficacy and safety of this procedure is fully established, it should belimited to high-risk patients.
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Homologous Recombination Deficiency and PARP Inhibition in Ovarian CancerAs part of our coverage of the 2017 ASCO Annual Meeting, we discuss homologous recombination deficiency in ovarian cancer and PARP inhibitors.
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Gemcitabine in Combination With Trastuzumab and/or Platinum Salts in Breast Cancer Cells With HER2 OverexpressionTrastuzumab (Herceptin) is an effective treatment in patients withHER2-overexpressing metastatic breast cancer. Risk of trastuzumabinducedcardiotoxicity raises concerns regarding combined use withanthracyclines or other potentially cardiotoxic agents followinganthracycline treatment. We characterized interactions betweentrastuzumab and gemcitabine (Gemzar) and the combination ofgemcitabine and cisplatin or carboplatin (Paraplatin) as such combinationsmight help reduce the risk of cardiotoxicity. Multiple drugeffect/combination index isobologram analysis was used to study theefficacy of chemotherapeutic drug plus trastuzumab combinations inHER2-overexpressing breast cancer cell lines. Combination index valueswere derived from parameters of the median effect plots, and statisticaltests were used to determine whether the mean combinationindex at multiple effect levels significantly differed from a combinationindex value of 1.0 (values < 1.0 indicate synergy; values > 1.0,antagonism; values equal to 1.0, additivity). At a wide range of clinicallyachievable drug concentrations, interactions between trastuzumaband gemcitabine were synergistic at low concentrations of gemcitabineand antagonistic at high concentrations. A consistent synergistic interactionwas observed with the three-drug combination of trastuzumabplus gemcitabine plus carboplatin or cisplatin. Available clinical dataon the use of trastuzumab plus gemcitabine, and trastuzumab plusgemcitabine/paclitaxel, as well as clinical data on the use ofgemcitabine/cisplatin in breast cancer, are discussed. These findingsindicate that trastuzumab plus gemcitabine and trastuzumab plusgemcitabine plus cisplatin or carboplatin are rational combinations toevaluate in clinical trials.
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Role of Obesity and Exercise in Breast Cancer SurvivorsAfter malignancies of the skin, breast cancer is the most common cancer
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Fraudulent Interpretation of Lab ResultsIn this edition, we offer an example of how clinicians and patients can be fooled and/or injured by fraudulent healthcare practitioners and their services. The clinical care team must be sure that the references it provides to patients are safe and reliable. Keep a list of reliable references and a list of those practitioners and services/treatments that should be avoided. Maintain an open door policy with your patients designed to encourage questions and exchange such information.
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A Strong Dose of HubrisFDA recently came close to taking away hope for thousands of terminally ill women. But at the last minute, the agency announced it was postponing until December whether to revoke approval of Avastin for advanced-stage breast cancer treatment.
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Gemcitabine/Paclitaxel as First-Line Treatment of Advanced Breast CancerGemcitabine (Gemzar) and paclitaxel exhibit good activity and goodsafety profiles when used alone and together in the treatment of advancedbreast cancer. In a phase II trial, 45 patients with metastaticbreast cancer received gemcitabine at 1,200 mg/m2 on days 1 and 8 andpaclitaxel at 175 mg/m2 on day 1 every 21 days. Twenty-seven patients(60.0%) had prior adjuvant therapy. Objective response was observedin 30 patients (objective response rate 66.7%, 95% confidence interval[CI] = 52%–71%), including complete response in 10 (22.2%) and partialresponse in 20 (44.4%). Median duration of response was 18 months(95% CI = 11–26.7 months), median time to tumor progression for theentire population was 11 months (95% CI = 7.1–18.7 months), medianoverall survival was 19 months (95% CI = 17.3–21.7 months), and the1-year survival rate was 69%. Treatment was well tolerated, with grade3/4 toxicities being infrequent. Grade 3/4 leukopenia, neutropenia, andthrombocytopenia were each observed in six patients (13.3%). No patientwas discontinued from the study due to hematologic ornonhematologic toxicity. Thus, the gemcitabine/paclitaxel combinationshows promising activity and tolerability when used as first-line treatmentin advanced disease. The combination recently has been shownto be superior to paclitaxel alone as first-line treatment in anthracyclinepretreatedadvanced disease according to interim results of a phase IIItrial and it should be further evaluated in comparative trials in breastcancer.
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Uracil/Tegafur Plus Oral Calcium Folinate in Advanced Breast CancerUracil and tegafur (in a molar ratio of 4:1 [UFT]) has proven activity against breast cancer and is delivered in an easy-to-administer oral formulation. Orzel, which combines UFT with the oral biomodulator, calcium folinate, may
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Exercise in Regulation of Inflammation-Immune Axis Function in Cancer Initiation and ProgressionThis article provides an overview of the current state of knowledge pertaining to exercise modulation of the inflammation-immune axis in cancer. The current evidence suggests that exercise may be a promising adjunctive strategy that can favorably alter numerous components of the immune system, which, in turn, may modulate tumorigenesis.
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Current Role of Retroperitoneal Lymph Node Dissection in Testicular CancerCarcinoma of the testis is the most common malignancy in males 15 to 35 years of age. Testicular cancer has become one of the most curable solid neoplasms and, as such, serves as a paradigm for the multimodality treatment of malignancies. The cure rate for patients with clinical stage I disease is nearly 100%, and patients with advanced disease now achieve complete remission rates of over 90%. The markedly improved outlook for patients with this cancer over the past 15 years has led to a reassessment of management options, especially in patients with clinical stage I disease. The realization that platinum-based chemotherapy could cure most patients with an advanced nonseminomatous germ cell tumor (NSGCT), especially those with minimal disease, led to the introduction of various strategies to decrease the morbidity associated with surgical management. These strategies include surveillance protocols, chemotherapy for clinical stage II disease, and observation protocols for a subset of patients with advanced disease who have had a partial response to chemotherapy. Retroperitoneal lymph node dissection (RPLND) has an important place in the management of both low- and high-stage testicular cancer. It offers the patient two basic benefits: accurate staging and the possibility of a surgical cure, even in the presence of metastatic disease. [ONCOLOGY 11(5):717-729, 1997]
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Estrogen Replacement Therapy for Breast Cancer PatientsFemale reproductive hormones cause breast cancer. Long-term use of postmenopausal hormones increases the risk of breast cancer. The apparent survival advantage seen in women diagnosed with breast cancer while taking
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Patterns of Chemotherapy Administration in Patients With Intermediate-Grade Non-Hodgkin’s LymphomaRecords from 653 patients treated between 1991 and 1998 in the Oncology Practice Patterns Study (OPPS) were analyzed to determine contemporary chemotherapy delivery patterns in patients with intermediate-grade non-
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Sentinel Lymph Node Biopsy in a Young Child With Thick Cutaneous MelanomaThe presence or absence oflymph node metastases is themost significant prognostic factorfor survival and recurrence in malignantmelanoma. Lymph node diseasedecreases the 5-year survival by 40%to 50%. The number of metastatic nodesand whether nodal metastases are clinicallyoccult or apparent are independentpredictors of survival.[1]
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Future of Proton-Beam Radiation Therapy Shines Among Inoperable Lung CancersResearch from Japan documenting remarkable survival rates among patients with inoperable lung cancer may only hint at the potential of proton-beam radiation therapy. The study out of the Proton Medical Research Center in Tennoudai, Japan, documented high survival rates for 55 patients suffering from stage I inoperable non-small-cell lung cancer.
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Anorexia/Cachexia in Patients with HIV: Lessons for the OncologistThis article provides a nice overview of HIV-associated wasting. The paper makes a number of strong points. In particular, it focuses on anorexia and decreased oral intake as key to wasting. In this vein, both the discussion by Von Roenn and Knopf and Tables 1 and 2 offer a very valuable review of the multiple reasons why HIV-infected patients may eat less. Given the many medications that we often need to use in these patients, the text discussion about the ways in which medications can result in decreased oral intake, reinforced by Table 2, is particularly useful.
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Interpreting Intratumoral Hypoxia: Can It Guide Therapy?The role of hypoxia as a key determinant of outcome for human cancers has encouraged efforts to noninvasively detect and localize regions of poor oxygenation in tumors. In this review, we will summarize existing and developing techniques for imaging tumoral hypoxia. A brief review of the biology of tumor oxygenation and its effect on tumor cells will be provided initially. We will then describe existing methods for measurement of tissue oxygenation status. An overview of emerging molecular imaging techniques based on radiolabeled hypoxic markers such as misonidazole or hypoxia-related genes and proteins will then be given, and the usefulness of these approaches toward targeting hypoxia directly will be assessed. Finally, we will evaluate the clinical potential of oxygen- and molecular-specific techniques for imaging hypoxia, and discuss how these methods will individually and collectively advance oncology.
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Clinical Oncology, Second EditionA comprehensive textbook on clinical oncology should have broad appeal to readers from various disciplines, including educators, clinicians, and scientists working with cancer patients. Students of the medical disciplines must also have a reference textbook to guide them in their educational exploration, whether they are in the field of medicine itself or in complementary areas. We look to comprehensive textbooks not only to provide us with the latest updates in different disease entities, but also to guide us by choosing the most relevant areas of study and investigation. The editors who compiled this textbook have met these challenges, while maintaining a readability that is suitable for various levels of expertise and comprehension
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Commentary (Kosuri/Otterson): Coming to Grips With Hand-Foot SyndromeIn this issue of ONCOLOGY,Scheithauer and Blum write aninformative review on the chemotherapeuticside effect of hand-footsyndrome, a not uncommon toxicityof several chemotherapeutic agents.They focus their discussion on capecitabine(Xeloda) and review the literatureregarding the best way to managehand-foot syndrome. Capecitabine isan oral fluoropyrimidine that is convertedto fluorouracil (5-FU) intratumorallyand delivers sustained 5-FU,thus simulating continuous-infusionregimens. It is now widely acceptedthat continuous-infusion regimens of5-FU are more effective and less toxicthan bolus regimens. However,historically, continuous-infusion regimensof 5-FU have not been in favorin the United States for logisticreasons.
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Contemporary Issues Surrounding Small Renal Masses: Evaluation, Diagnostic Biopsy, Nephron Sparing, and Novel Treatment ModalitiesIn this review, we summarize the diagnosis of small renal masses, the role of renal mass biopsy, different treatment strategies, and future directions, including emerging molecular biomarkers.
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Sorafenib for HCC: A Pragmatic PerspectiveThe diagnosis and treatment of hepatocellular carcinoma (HCC) constitute a complex and challenging clinical paradigm.
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Next Steps in the Management of EGFR Exon 20 Insertion–Positive mNSCLCClosing out their discussion on mobocertinib data and the EXCLAIM cohort, experts share hope for the future management of the EGFR exon 20 insertion–positive mNSCLC.
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Robotics in Head and Neck Cancer: Future OpportunitiesA series of promising new advances have emerged in H&N oncology in recent years. Among these are the advancement of highly conformal radiation delivery techniques (e.g. IMRT, protons); the successful introduction of molecular targeted therapies (e.g. cetuximab); the recognition of HPV as a powerful prognostic biomarker; and the development of minimally invasive surgical techniques. The application of transoral robotic surgery (TORS) in H&N cancer is reviewed by Bhayani et al in this issue of ONCOLOGY[1].
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Navigating a ‘Revolutionary Era’ of Targeted Therapy in Pancreatic CancerThe key to the future of pancreatic cancer treatment is immunotherapy, according to Gregory L. Beatty, MD, PhD.
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New Targets and New Mechanisms in Lung CancerThis review will describe the well-known use of VEGF antibodies; the current uses of EGFR and ALK tyrosine kinase inhibitors; newer agents being used against MET, FGFR, and other intracellular targets; insights regarding the field of immunotherapy in lung cancer; and finally, newer developments in chemotherapy.
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ASTRO 2017: Long-Term Data Support Single SBRT Dose in Certain Early Lung CancersThis video reviews long-term results of the NRG Oncology RTOG 0915 trial, a randomized phase II study that compared stereotactic body radiation therapy delivered in one fraction vs four fractions for stage I peripheral non–small-cell lung cancer patients with unresectable disease.
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Primary Carcinoid Tumors of the Lung: A Role for RadiotherapyPrimary neuroendocrine neoplasms of the lung represent a clinical spectrum of tumors ranging from the relatively benign and slow-growing typical carcinoid to the highly aggressive small-cell lung carcinoma. The rarity of carcinoids has made the role of radiation therapy in their management controversial. This review considers the results of published studies to generate treatment recommendations and identify areas for future research. Surgery remains the standard of care for medically operable disease. Histology plays the most important role in determining the role of adjuvant radiation. Resected typical carcinoids likely do not require adjuvant therapy irrespective of nodal status. Resected atypical carcinoids and large-cell neuroendocrine carcinomas have a significant risk of local failure, for which adjuvant radiation likely improves local control. Definitive radiation is warranted in unresectable disease. Palliative radiation for symptomatic lesions has demonstrated efficacy for all histologies. Collaborative group trials are warranted.
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Updated ASCO Guidelines for Optimal Small Cell Lung Cancer ManagementPractices are on the cusp of better understanding small cell lung cancer that in turn can help to advance treatment strategies for patients, says Gregory Peter Kalemkerian, MD.
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Use of Bisphosphonates in Patients With Metastatic Bone DiseaseThe bisphosphonates have now joined an elite group of drugs that have annual sales greater than $1 billion. Although the major therapeutic target of these agents is osteoporosis, their use in cancer, particularly in osteolytic bone disease due to breast cancer and myeloma, is growing very rapidly. Pamidronate (Aredia), the only bisphosphonate currently approved for this indication in the United States, is now prescribed for the majority of patients with myeloma, as well as a substantial number of patients with breast cancer.
