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DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology, 9e
Vincent T. DeVita, Jr., Theodore S. Lawrence, Steven A. Rosenberg
Copyright   •   Dedication   •   Contributors   •   Preface   •   Acknowledgments   •   Updating Authors
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April 29, 2013
Chapter 76: Small Cell and Neuroendocrine Tumors of the Lung >
Small Cell Lung Cancer
Updated By Christopher G. Azzoli (April 29, 2013) Screening CT scans detect non-small cell lung cancers at an earlier stage compared to chest x-ray, or no screening, and can decrease lung cancer-specific mortality in heavy smokers. (National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. N Engl J Med 2011;365:395-409. 21714...
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April 04, 2013
Chapter 87: Gastrointestinal Stromal Tumor >
The Development of A Molecular Understanding of GIST
Updated By Aimee Crago (April 04, 2013) Next generation sequencing of these KIT/PDGFRA wild-type GISTS shows dysregulation of succinate dehydrogenase expression is due to a mutation in the SDHA gene in some patients. (Italiano A, Chen CL, Sung YS, et al. BMC Cancer 2012;12:408. 22974104 )...
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April 04, 2013
Chapter 87: Gastrointestinal Stromal Tumor >
Clinical Considerations
Updated By Aimee Crago (April 04, 2013) Patients with GIST have an increased risk of metachronous desmoid tumor formation. (Dumont AG, Rink L, Godwin AK, et al. Ann. Oncol 2012; 23:1335-40. 21994214 )...
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April 04, 2013
Updated By Aimee Crago (April 04, 2013) The characterization of a mouse model that develops imatinib-resistant GIST has the potential to provide a new method for examining novel treatments in vivo. (Bosbach B, Deshpande S, Rossi F, et al. Proc Natl Acad Sci U S A 2012;109):E2276-83.PNAS 109(34):E2276-83. 22652566 )...
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Updated By Aimee Crago (April 04, 2013) A randomized trial examining response to imatinib (Gleevec) after drug interruption in non-progressing patients demonstrates that response is significantly less robust when the drug was restarted; interruption of therapy may contribute to acquisition of resistant disease. (Patrikidou A, Chabaud S, R...
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Updated By Aimee Crago (April 04, 2013) A phase III trial of the TKI inhibitor regorafenib– which targets VEGF receptors, KIT, PDGF receptors, and FGF receptors–has been completed in patients with prior failure of imatinib and sunitinib. Progression free survival in patients receiving regorafenib is 4.8 months compared to patients receiv...
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April 04, 2013
Chapter 93: Cancer of the Kidney >
Localized Renal Carcinoma
Updated By Dean Bajorin (April 04, 2013) A randomized trial attempted to address whether nephron-sparing surgery was sufficient to manage small tumors. (Van Poppel H, Da Pozzo L, Albrecht W, et al. Eur Urol 2011;59:543-52. 21186077 ) In this EORTC phase III trial, patients with solitary ≤5 cm lesions suspected to be ren...
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April 04, 2013
Chapter 93: Cancer of the Kidney >
Metastatic Renal Carcinoma
Updated By Dean Bajorin (April 04, 2013) Axitinib is a selective second-generation VEGF inhibitor with a relative potency >50 times greater than that of the first-generation VEGFR inhibitors. Early clinical data showed an encouraging response rate both in treatment-naïve patients as well as those previously treated with first-generation VE...
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April 04, 2013
Chapter 95: Cancer of the Bladder, Ureter, and Renal Pelvis >
Cancer of the Bladder
Updated By Dean Bajorin (April 04, 2013) Updated data are available. Despite a response rate that was superior in the three drug arm (55.5% versus 43.6%, P = .0031) and a median overall survival that was slightly longer in patients receiving the third drug (15.8 months versus 12.7), the hazard ratio for survival did not achieve statistical...
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Updated By Dean Bajorin (April 04, 2013) Maintenance BCG therapy for up to 3 years is a standard of care although patients frequently discontinue therapy early due to bladder toxicity. An EORTC phase III trial in over 1300 patients sought to evaluate whether a 1/3rd dose versus full dose and 1-year treatment versus 3-year treatment cou...
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April 04, 2013
Chapter 106: Malignant Tumors of the Breast >
Endocrine Therapy
Updated By Gina G. Chung (April 04, 2013) More recently information was published: of 732 women with ER-positive breast cancer, tamoxifen significantly reduced the risk for subsequent breast cancer at 10 years (HR 0.49; P < 0.001) and at overall follow-up (HR 0.60; P = 0.003). (Allred DC, Anderson SJ, Paik S, et al. J Clin Oncol 2012;30:126...
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April 04, 2013
Chapter 106: Malignant Tumors of the Breast >
Management of the Axilla
Updated By Gina G. Chung (April 04, 2013) More recently, the ACOSOG Z0011 trial assessed the effect on survival of the standard of care management of sentinel lymph node positive disease. This was a prospective randomized study to address the need for completion axillary dissection in clinically node-negative women found to have macrometast...
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April 04, 2013
Chapter 106: Malignant Tumors of the Breast >
Adjuvant Systemic Therapy
Updated By Gina G. Chung (April 04, 2013) Two studies have recently been published that contradict the significance of the above pharmacogenomic finding. Rae et al. (Rae JM, Drury S, Hayes DF, et al. J Natl Cancer Inst 2012;104:452-60. 22395643 ) and Regan et al. (Regan MM, Leyland-Jones B, Bouzyk M, et al. J Natl Cancer...
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April 04, 2013
Chapter 106: Malignant Tumors of the Breast >
Metastatic Disease
Updated By Gina G. Chung (April 04, 2013) A recent study, though, showed improved progression free survival and overall survival with a combination of fulvestrant and anastrozole compared to anastrozole alone in women with previously untreated metastatic breast cancer. (Mehta RS, Barlow WE, Albain KS, et al. N Engl J Med 2012; 367:435-44. ...
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Updated By Gina G. Chung (April 04, 2013) Preclinical evidence has suggested that cross-talk and upregulation of numerous signal transduction pathways may be important in resistance to treatment. The results of the BOLERO-2 trial have recently led to the approval of the mTOR inhibitor everolimus in the advanced setting. (Baselga J, Campone ...
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Updated By Gina G. Chung (April 04, 2013) More recently, combining multiple different HER2-targeting agents has shown promise. Pertuzumab, the humanized monoclonal antibody that binds both HER2 and HER3, has shown synergy when combined with trastuzumab in patients with HER2 amplified breast cancer. Results from the CLEOPATRA trial showed th...
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April 04, 2013
Updated By Tobias Carling (April 04, 2013) More work is needed better clarify which patients with differentiated thyroid cancer may have the greatest benefit from TKIs. (Leboulleux S, Bastholt L, Krause T, et al. Lancet Oncol 2012;13:897-905. 22898678 ; Bible KC. Lancet Oncol 2012;13:854-5. Epub 2012 Aug 14. 22898...
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April 04, 2013
Chapter 108: Thyroid Tumors >
Medullary Thyroid Carcinoma
Updated By Tobias Carling (April 04, 2013) The phase III data of vandetanib treatment in MTC was recently published. (Wells SA Jr, Robinson BG, Gagel RF, et al. J Clin Oncol 2012;30:134-41. 22025146 )...
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April 04, 2013
Chapter 108: Thyroid Tumors >
Evaluation of the Thyroid Nodule
Updated By Tobias Carling (April 04, 2013) Recently, the initial data of using a gene expression panel to further characterize thyroid nodules with an “indeterminate” FNA was presented. Further validation of the role of mRNA expression levels in aiding in the cytological diagnosis of thyroid nodule is needed. (Alexander EK, Kennedy GC, Baloc...
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April 04, 2013
Updated By Tobias Carling (April 04, 2013) Recently, two studies were published showing that low-dose radioactive iodine ablation is likely sufficient for the vast majority of patients with “low-risk” differentiated thyroid cancer. (Schlumberger M, Catargi B, Borget I, et al. N Engl J Med 2012;366:1663-73. 22551127 ; Mall...
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April 04, 2013
Chapter 110: Adrenal Tumors >
Adrenocortical Cancer
Updated By Tobias Carling (April 04, 2013) The results from the FIRM-ACT study have now been published. The study group demonstrated that rates of response and progression-free survival were significantly better with etoposide-doxorubicin-cisplatin plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates o...
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Updated By Tobias Carling (April 04, 2013) The first phase II study using a tyrosine kinase inhibitor (TKI) in patients who had failed conventional treatment was recently published, demonstrating modest activity. (Kroiss M, Quinkler M, Johanssen S, et al. J Clin Endocrinol Metab 2012;97:3495-503. 22837187 ) ...
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April 04, 2013
Chapter 112: Neuroendocrine (Carcinoid) Tumors and the Carcinoid Syndrome >
Carcinoid Syndrome
Updated By Tobias Carling (April 04, 2013) The results of a phase II study using pasireotide (SOM320) in patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR was recently published. (Kvols LK, Oberg KE, O'Dorisio TM, et al. Endocr Relat Cancer. 2012 Sep 14;19(5):657-66. 22807497 ) ...
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April 04, 2013
Chapter 113: Multiple Endocrine Neoplasias >
Multiple Endocrine Neoplasia Type 1
Updated By Tobias Carling (April 04, 2013) Updated and comprehensive clinical practice guidelines for MEN1 were recently published. (Thakker RV, Newey PJ, Walls GV, et al. J Clin Endocrinol Metab 2012 Sep;97:2990-3011. 22723327 ) ...
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April 04, 2013
Chapter 115: Soft Tissue Sarcoma >
Anatomic and Age Distribution and Pathology
Updated By Aimee Crago (April 04, 2013) Amplification of the PAX7-FOXO1 fusion is also observed in these tumors and is associated with improved outcome though the molecular mechanisms that underpin this observation have not been delineated. (Duan, F., Smith, L.M., Gustafson, D.M., et al. Genes Chromosomes Cancer 2012 Jul;51(7):662-74. ...
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Updated By Aimee Crago (April 04, 2013) While alterations in p53 and PTEN pathways are commonly observed in undifferentiated pleomorphic sarcoma and leiomyosarcoma, these aberrancies are rarely detected in angiosarcoma. (Italiano A, Chen CL, Thomas R, et al. Cancer 2012;118:5878-87. 22648906 )...
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April 04, 2013
Updated By Aimee Crago (April 04, 2013) Formal publication of outcomes in this study continue to show no evidence of survival benefit related to adjuvant chemotherapy. Neither overall or relapse free survival differed significantly at median follow-up of 8 years (hazard ratios 0.94 and 0.91, respectively). The implications of the study wi...
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April 04, 2013
Chapter 115: Soft Tissue Sarcoma >
Anatomic and Age Distribution and Pathology
Updated By Aimee Crago (April 04, 2013) Rare example of aggressive type fibrous histiocytomas have been observed (‘malignant dermatofibroma’). These lesions have a propensity for local recurrence, have been reported to metastasize and can cause death in a small number of patients. Copy number alterations have been detected in these tumors...
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April 04, 2013
Chapter 115: Soft Tissue Sarcoma >
Diagnosis and Staging
Updated By Aimee Crago (April 04, 2013) Of 1463 histologic specimens obtained from patients with connective tissue tumors in France and Italy, grade and histologic subtype were confirmed by an expert pathologist in only 56% of cases. In 35% of patients, discordance was related to a different characterization of histologic subtype or grad...
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April 04, 2013
Updated By Aimee Crago (April 04, 2013) The utility of RT in the setting of retroperitoneal sarcoma is continuously debated among physicians treated this disease. In attempt to provide definitive guidance, the EORTC has opened a randomized, phase III trial (EORTC 62092 - 22092) comparing relapse free survival in patients treated with neoa...
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Updated By Aimee Crago (April 04, 2013) In a recent attempt to quantify outcomes in patients receiving systemic therapy for metastatic sarcoma, the SABINE investigators examined 213 patients treated in North America and Europe. Patients were treated with an average of 2.7 lines of chemotherapy. A favorable response was observed in 83% ...
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Updated By Aimee Crago (April 04, 2013) The PALETTE study has recently been published, examining the role of Pazopanib, a multitargeted tyrosine kinase inhibitor, in treatment of refractory patients. In this phase III, randomized controlled trial, progression free survival was 4.6 months in patients who received the drug versus 1.6 months...
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Updated By Aimee Crago (April 04, 2013) Case reports suggest that patients with solitary fibrous tumors and extraskeletal myxoid chondrosarcomas may respond to sunitinib. (Stacchiotti S, Negri T, Libertini M, et al. Anns Oncol 2012;23:3171-9. 22711763 ; Stacchiotti S, Dagrada GP, Morosi C, et al. Clin Sarcoma Res 2-12...
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Updated By Aimee Crago (April 04, 2013) In a small randomized trial examining 90 patients with metastatic or unresectable leiomyosarcoma (uterine and non-uterine), patients were randomized to receive either gemcitabine alone or in combination with docetaxel. Response rates and progression free survival did not differ significantly betwee...
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April 04, 2013
Chapter 116: Sarcomas of Bone >
Malignant Bone Tumors
Updated By Aimee Crago (April 04, 2013) A randomized trial performed by the Italian Sarcoma Group (ISG/OS-1) confirmed the fact that ifosfamide adds little clinical benefit in the adjuvant setting. The 246 patients were randomized to receive MTX-CDP-ADM with or without ifosfamide. (Patients not receiving ifosfamide preoperatively were gi...
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Updated By Aimee Crago (April 04, 2013) Multiple studies are currently exploring the use of insulin growth factor receptor inhibition in the management of Ewing’s sarcoma. Stabilization of disease or partial response has been observed in as many as 50% of patients with refractory disease. Administered as single agents, durable response is...
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April 04, 2013
Chapter 117: Cancer of the Skin >
Topical Therapy for Skin Cancer
Updated By Mario Snolz (April 04, 2013) (Gupta AK, Paquet M, Villanueva E, Brintnell W. Cochrane Database Syst Rev 2012 Dec 12;12:CD004415. 23235610 )...
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April 04, 2013
Chapter 117: Cancer of the Skin >
Basal Cell Carcinoma
Updated By Michael Girardi (April 04, 2013) The understanding of the key role of the hedgehog pathway in BCC pathogenesis has led to the development and clinical testing of a novel therapeutic inhibitor. Vismodegib binds directly to and blocks the smoothened (SMO) protein, inhibiting the activation and nuclear localization of GLI transcriptio...
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April 04, 2013
Chapter 117: Cancer of the Skin >
Pathogenesis
Updated By Michael Girardi (April 04, 2013) Increased detection techniques reveal that virtually all MCC contain MCPyV (Rodig SJ, Cheng J, Wardzala J, et al. J Clin Invest 2012;122:4645-53. 23114601 ) and that both CD4+ and CD8+ anti-viral T cells are detectable within tumors and the blood of MCC patients. (Iyer JG, Afanas...
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April 04, 2013
Chapter 117: Cancer of the Skin >
Basal Cell Carcinoma
Updated By Michael Girardi (April 04, 2013) BCC is substantially more common among survivors of childhood cancers, principally due to previous treatment with ionizing radiation therapy alone or in combination with chemotherapy. In affected individuals with a history of childhood cancers, BCC developed between 20 and 39 years of age, with an i...
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April 04, 2013
Chapter 119: Cutaneous Melanoma >
Combination Chemotherapy
Updated By Mario Sznol (April 04, 2013) The results of S0008 were presented at ASCO 2012 (see section Cytotoxic Chemotherapy and Combination Chemotherapies in Adjuvant Therapy of Melanoma).)...
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April 04, 2013
Chapter 119: Cutaneous Melanoma >
Rationale for Targeted Therapy in Melanoma
Updated By Mario Sznol (April 04, 2013) New names have been assigned to two of these inhibitors: GSK2118436 is now dabrafenib, (http://www.cancer.gov/drugdictionary?cdrid=641977 (Accessed January 28, 2013)) and GSK 1120212 is now trametinib. (http://www.cancer.gov/drugdictionary?CdrID=599034 (Accessed January 28, 2013))...
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Updated By Mario Sznol (April 04, 2013) With further follow up, median survival was 15.9 months. (Sosman JA, Kim KB, Schuchter L, et al. N Engl J Med 2012;366:707-14. 22356324 )...
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Updated By Mario Sznol (April 04, 2013) With additional follow–up, the median PFS in the vemurafenib arm increased to 6.9 months, objective response rate increased to 57%, and median survival was estimated at 13.6 months. (Chapman P, Hauschild A, Robert C, et al. J Clin Oncol 2012;30 (No 15_suppl; abstr 8502) . 2012 ASCO Annual Meeting P...
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Updated By Mario Sznol (April 04, 2013) In a phase 3 trial in which 187 patients with documented tumor V600E mutations were randomized to receive dabrafenib 150 mg po twice daily versus dacarbazine 1000 mg/m2 IV q3w, dabrafenib increased median PFS from 2.7 to 5.1 months. (Hauschild A, Grob JJ, Demidov lV, et al. Lancet 2012; 380: 358–65....
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Updated By Mario Sznol (April 04, 2013) In a subsequent phase 3 trial, 322 patients with tumor V600E or V600K mutations were assigned 2:1 to receive GSK1120212 (trametinib) or investigator choice of either dacarbazine or paclitaxel. (Flaherty KT, Robert C, Hersey P, et al. N Engl J Med 2012;367:107-14. 22663011 ) Trame...
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Updated By Mario Sznol (April 04, 2013) Preclinical and correlative studies indicate that a major mechanism of resistance to selective BRAF inhibitors is reactivation of signaling through MEK. (Nazarian R, Shi H, Wang Q, et al. Nature 2010;468:973-7. 21107323 ) Trametinib alone demonstrated minimal activity in patients...
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April 04, 2013
Chapter 119: Cutaneous Melanoma >
Adjuvant Systemic Therapy (Stages IIB, IIC, and III)
Updated By Mario Sznol (April 04, 2013) Ipilimumab, a monoclonal antibody that inhibits the immune co-inhibitory molecule, cytotoxic T cell antigen-4 (CTLA-4), was recently shown in phase III randomized trials to prolong survival in metastatic melanoma (see Management of Stage IV Melanoma below). Ipilimumab is currently being studied in ...
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April 04, 2013
Chapter 119: Cutaneous Melanoma >
Management of Distant Metastases of Melanoma (Stage IV)
Updated By Mario Sznol (April 04, 2013) Nab-paclitaxel 150 mg/m2 weekly × 3 q4w was compared to DTIC in 529 chemotherapy-naive patients with metastatic disease. (Hersh E, Del Vecchio M, Brown M, et al. Pigment Cell Melanoma Res 2012;25(6): 863. http://www.onclive.com/publications/obtn/2012/November-2012/Nab-Paclitaxel-Extends-PFS-Versus-S...
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April 04, 2013
Chapter 121: Neoplasms of the Central Nervous System >
Epidemiology of Brain Tumors
Updated By Joachim Baehring (April 04, 2013) However, more recently it was shown in an animal experiment that gliomas can originate from differentiated cells in the central nervous system including cortical neurons. (Friedmann-Morvinski D, Bushong EA, Ke E, et al. Science 2012;338:1080-4. 23087000 )...
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April 04, 2013
Chapter 121: Neoplasms of the Central Nervous System >
Chemotherapy and Targeted Agents
Updated By Joachim Baehring (April 04, 2013) Bayesian adaptive randomized designs in clinical trials may allow for more efficient trials compared to those with balanced randomization. (Trippa L, Lee EQ, Wen PY, et al. J Clin Oncol 2012;30:3258-63. 22649140 )...
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April 04, 2013
Chapter 121: Neoplasms of the Central Nervous System >
Specific Central Nervous System Neoplasms
Updated By Joachim Baehring (April 04, 2013) Missense mutations of the V600E type in the v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene were identified in these non-infiltrative neoplasms. The highest frequencies were found in pleomorphic xanthoastrocytomas (66%; 65 % in its anaplastic variant), gangliogliomas (18%), and pilocytic ...
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Updated By Joachim Baehring (April 04, 2013) Subependymal giant cell astrocytomas can be effectively treated with everolimus. In a prospective randomized study, 35% of patients in the everolimus group had at least 50% reduction in the volume of their tumor versus none in the placebo group. (Franz DN, Belousova E, Sparagana S, et al. Lancet 201...
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Updated By Joachim Baehring (April 04, 2013) Newer study data indicate patients were randomly assigned to RT alone or RT followed by six cycles of PCV; 251 patients were accrued from 1998 to 2002. Progression-free survival but not overall survival were improved in the RT+PCV group compared to RT alone. (Shaw EG, Wang M, Coons SW, et al. J Clin...
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Updated By Joachim Baehring (April 04, 2013) Long-term results of this study demonstrated that patients with co-deleted tumors lived longer than those with non–co-deleted tumors irrespective of therapy, and the median survival of those with co-deleted tumors treated with PCV plus RT was twice that of patients receiving RT (14.7 vs. 7.3 years)....
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Updated By Joachim Baehring (April 04, 2013) Long-term follow up showed that PFS and OS were better in the PCV group, but overall survival was not different (OS in the RT/PCV arm 42.3 months, in the RT arm 30.6 months). In patients with a 1p/19q co-deletion, there was a trend to more benefit from adjuvant PCV (OS not reached in the RT/PCV grou...
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Updated By Joachim Baehring (April 04, 2013) Non-inferiority of temozolomide compared to standard radiotherapy was demonstrated in a German trial of GBM patients older than 65 years. (Wick W, Platten M, Meisner C, et al. Lancet Oncol 2012;13:707–15. 22578793 )...
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April 04, 2013
Chapter 121: Neoplasms of the Central Nervous System >
Primitive Neuroectodermal or Embryonal Central Nervous System Neoplasms
Updated By Joachim Baehring (April 04, 2013) This regimen yielded promising results in the subgroup of patients with metastatic medulloblastoma, as well. (Jakacki RI, Burger PC, Zhou T, et al. J Clin Oncol 2012;30:2648-53. 22665539 )...
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Updated By Joachim Baehring (April 04, 2013) The addition of conformal radiation therapy limited to the posterior fossa and primary site to chemotherapy (cyclophosphamide, vincristine, cisplatin, etoposide) in children between 8 months and 3 years old with nonmetastatic medulloblastoma increased event-free survival compared with the use of pos...
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April 04, 2013
Chapter 121: Neoplasms of the Central Nervous System >
Specific Central Nervous System Neoplasms
Updated By Joachim Baehring (April 04, 2013) In another prospective randomized study of patients with GBM older than 60 years, temozolomide was found to be superior to standard radiotherapy (median overall survival 8.3 months vs 6.0 months). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiothera...
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April 04, 2013
Chapter 121: Neoplasms of the Central Nervous System >
Primitive Neuroectodermal or Embryonal Central Nervous System Neoplasms
Updated By Joachim Baehring (April 04, 2013) Four tumor subgroups with distinct clinical, biological, and genetic profiles are currently identified: tumors with activated wingless pathway signaling; tumors with sonic hedgehog pathway activation; group 3 and group 4 tumors. A recently published integrative deep-sequencing analysis of 125 tumour...
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April 04, 2013
Chapter 123: Solid Tumors of Childhood >
Neuroblastoma
Updated By David Poplack (April 04, 2013) Recent evidence suggests that co-expression of ALK and MYCN leads to development of neuroblastoma with an earlier onset. A higher penetrance and enhanced lethality in a mouse model suggesting a pathogenic role for ALKF1174L in neuroblastomas overexpressing MYCN. (Berry T, Luther W, Bhatnagar N, et a...
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April 04, 2013
Chapter 123: Solid Tumors of Childhood >
Wilms’ Tumor
Updated By David Poplack (April 04, 2013) A recent update from the COG suggests that patients with CT-only lung lesions may have improved EFS but not OS from the addition of doxorubicin but do not appear to benefit from pulmonary radiation. (Grundy PE, Green DM, Dirks C, et al. Pediatric Blood Cancer 2012;59:631-5. 22422736 ...
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April 04, 2013
Chapter 123: Solid Tumors of Childhood >
Rhabdomyosarcoma
Updated By David Poplack (April 04, 2013) In girls with nonbladder genitourinary primary sites there is still a need for radiation therapy as part of their treatment. Also in patients with low-risk rhabdomyosarcoma, reduced-dose radiotherapy does not compromise local control for patients with microscopic tumor after surgical resection or wi...
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April 04, 2013
Chapter 123: Solid Tumors of Childhood >
Neuroblastoma
Updated By David Poplack (April 04, 2013) A small molecule inhibitor of ALK and C-Met with encouraging preclinical data is currently in a clinical phase I/II trial within the Children’s Oncology Group (COG) opening up a promising future for personalized therapy in patients with neuroblastoma. (National Cancer Institute (NCI). Crizotinib in ...
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April 04, 2013
Chapter 124: Leukemias and Lymphomas of Childhood >
Leukemias
Updated By David Poplack (April 04, 2013) In addition to the above report (by Pui et al), another recent report highlights racial and ethnic disparities in access to care and adherence to treatment, and the consequent adverse impact on survival. Bhatia et al found that adherence to oral mercaptopurine during ALL maintenance therapy was sign...
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Updated By David Poplack (April 04, 2013) For example, whole genome sequencing recently identified novel alterations that give risk to a gene expression profile similar to BCR-ABL1-positive ALL, and may be similarly sensitive to tyrosine kinase inhibitor therapy. (Roberts KG, Morin RD, Zhang J, et al. Cancer Cell 2012;22:153-66. 228...
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Updated By David Poplack (April 04, 2013) Numerous translocations occur in T-lineage ALL, but they are not generally associated with prognosis, in contrast to many B-lineage translocations. Recently a subgroup constituting approximately 10% of T-lineage ALL has been identified which bears a distinctive immunophenotype, a gene expression sig...
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Updated By David Poplack (April 04, 2013) Blinatumomab, a CD19/CD3-bispecific T-cell engaging (BiTE) antibody, has shown promising response rates and prolonged survival in relapsed B-lineage ALL in adults, and is currently in a Phase II international trial in pediatrics. (Topp MS, Kufer P, Gökbuget N, et al. J Clin Oncol 2011;29:2493-8. ...
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Updated By David Poplack (April 04, 2013) Two novel biologic agents have shown promise in early phase clinical studies, the proteasome inhibitor bortezomib (Horton TM, Pati D, Plon SE, et al. Clin Cancer Res 2007;13:1516-22. 17332297 ) and the kinase inhibitor sorafenib (which inhibits FLT3), (Widemann BC, Kim A, Fox E, ...
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April 04, 2013
Chapter 124: Leukemias and Lymphomas of Childhood >
Lymphomas
Updated By David Poplack (April 04, 2013) Increasingly, PET is being used to assess early response and guide further treatment, as opposed to exclusive reliance on CT scans. (Engert A, Haverkamp H, Kobe C, et al. Lancet 2012; 379(9828):1791-9. 22480758 )...
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April 04, 2013
Chapter 126: Hodgkin Lymphoma >
Immunology of Hodgkin Lymphoma
Updated By Paul Barr (April 04, 2013) Tumor-associated macrophages using immunohistochemistry for CD68 and Cd163 were evaluated in patient samples collected from E2496, a randomized trial comparing ABVD and Stanford V. The results demonstrated that increased CD68 and CD163 were associated with an inferior failure free survival and overa...
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April 04, 2013
Chapter 126: Hodgkin Lymphoma >
Treatment for Early Favorable Hodgkin Lymphoma
Updated By Paul Barr (April 04, 2013) After 12 years, the overall survival rate was recently reported to be superior for the ABVD-only group (94%) as compared to those receiving radiation therapy (87%) despite an inferior 12-year freedom from disease progression, 87% vs 92%. respectively. These differences were largely a result of late ...
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April 04, 2013
Chapter 126: Hodgkin Lymphoma >
Early Unfavorable Hodgkin Lymphoma
Updated By Paul Barr (April 04, 2013) Longer follow-up does support this statement. At 12 years, a superior overall survival but inferior freedom from disease progression was demonstrated with ABVD alone compared to combined modality therapy. Late events in those receiving subtotal nodal irradiation largely accounts for these difference...
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April 04, 2013
Chapter 126: Hodgkin Lymphoma >
Advanced Stages of Hodgkin Lymphoma
Updated By Paul Barr (April 04, 2013) Initial results from this trial–where ABVD is compared to BEACOPP 4 + 4 in advanced stage patients also having an international prognostic score of 3 or greater–have demonstrated no significant difference in the primary endpoint, event-free survival, albeit at a median follow up of only 3.8 years. (...
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Updated By Paul Barr (April 04, 2013) The recently completed GHSG HD15 trial suggests six cycles of BEACOPP escalated may retain the efficacy observed with 8 cycles in HD9 and HD12 with less acute and long-term toxicity. In this non-inferiority study 2126 patients were randomized to eight courses of BEACOPP escalated, 6 courses of BEACO...
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April 04, 2013
Chapter 126: Hodgkin Lymphoma >
New Drugs in Hodgkin Lymphoma
Updated By Paul Barr (April 04, 2013) Further, brentuximab has enabled select patients to proceed to allogeneic stem cell transplantation and did not appear to adversely affect stem cell engraftment, graft vs host disease or survival. (Chen R, Palmer JM, Thomas SH, et al. Blood 2012;119:6379 -81. 22611160 ) Brentuxim...
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Updated By Paul Barr (April 04, 2013) As 20%-30% of classical HLs are CD20+ and further based on its microenvironmental effects, the addition of rituximab to ABVD is being investigated. Two recent phase II studies demonstrate the combination to be safe and without an obvious diminution in efficacy. (Younes A, Oki Y, McLaughlin P, et al....
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April 04, 2013
Chapter 127: Non-Hodgkin Lymphomas >
Specific Disease Entities
Updated By Paul Barr (April 04, 2013) With the availability of immunohistochemical testing to demonstrate nuclear MYC expression, several groups are investigating the impact of protein expression as compared to translocations involving MYC in addition to BCL2. The results to date have demonstrated that roughly 1/3 of patients with DLBCL...
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April 04, 2013
Chapter 127: Non-Hodgkin Lymphomas >
Mature T-Cell and NK Cell Neoplasms
Updated By Paul Barr (April 04, 2013) The Nordic Lymphoma Group recently published the final results of their prospective phase II study evaluating dose dense CHOEP followed by autologous stem cell transplantation in PTCL. Of 166 patients enrolled, 115 underwent stem cell transplantation. Overall and progression free survival for the en...
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Updated By Paul Barr (April 04, 2013) Two hundred forty three patients with angioimmunoblastic T-cell lymphoma were included in the International Peripheral T-Cell Lymphoma Project. The cohort demonstrated a 5-year overall survival of 32% and a 5-year failure free survival of 18%. The majority of patients were treated with anthracyclin...
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April 04, 2013
Chapter 127: Non-Hodgkin Lymphomas >
Specific Disease Entities
Updated By Paul Barr (April 04, 2013) It was recently demonstrated that somatic mutations in myeloid differentiation primary response gene 88 (MYD88) are found in 90% of patients with Waldenstrom’s macroglobulinemia. High nuclear levels of NF-κB p65 in these patients suggesting aberrant NF-κB pathway activation may contribute to the pat...
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Updated By Paul Barr (April 04, 2013) Results from the National LymphoCare Study challenge the paradigm that radiation therapy should be the standard for stage I follicular lymphoma. For 206 patients with stage I disease confirmed by CT scans or PET and bone marrow biopsy, the progression free survival was significantly improved in thos...
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Updated By Paul Barr (April 04, 2013) Single institution results from M. D. Anderson for nonmyeloablative allogeneic transplantation in follicular lymphoma patients have been encouraging albeit in a select patient population. Eleven year overall and progression free survivals were 78 and 72% respectively for patients conditioned with fl...
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Updated By Paul Barr (April 04, 2013) Based on these and other results, the addition of cytarabine to induction therapy appears to improve outcomes as compared to historic controls. Phase II results from the GELA demonstrated a 5-year event free survival of 64% and overall survival of 75% for patients receiving 3 cycles of RCHOP, 3 cycl...
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Updated By Paul Barr (April 04, 2013) Rituximab administered in maintenance fashion appears to benefit older patients not eligible for high-dose therapies. A recently published international trial reported on 560 patients initially randomized to FCR or RCHOP followed by a second randomization in responders to maintenance rituximab or in...
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Updated By Paul Barr (April 04, 2013) Consolidative radioimmunotherapy has also been investigated in mantle cell lymphoma in attempt to prolonged patients’ duration of remission. Patients enrolled in a phase II Eastern Cooperative Oncology Group study received 4 cycles of RCHOP followed by yttrium-90 ibritumomab. In these 52 patients, t...
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April 04, 2013
Chapter 127: Non-Hodgkin Lymphomas >
Mature T-Cell and NK Cell Neoplasms
Updated By Paul Barr (April 04, 2013) Recent published data serve as a benchmark for therapeutic outcomes in this disease. The Japan Clinical Oncology Group reported on 33 patients with early stage disease receiving combination chemoradiotherapy. Patients received aggressive chemotherapy with concurrent involved field radiation to 50Gy....
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April 04, 2013
Updated By Paul Barr (April 04, 2013) The anti-CD30 immunoconjugate brentuximab vedotin is being investigated in CTCL based on CD30 cell surface expression in some patients and promising efficacy in peripheral T cell lymphoma. (Desai A, Telang GH, Olszewski AJ. Ann Hematol 2012 Oct 21. [Epub ahead of print] 23086510 ...
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April 04, 2013
Updated By Paul Barr (April 04, 2013) The EORTC recently presented their final results from a phase III clinical trial comparing bexarotene and PUVA compared to PUVA alone in patients with stage IB and IIA disease. The study was closed prematurely due to low accrual. Forty-five patients received PUVA and 48 received the combination. ...
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April 04, 2013
Chapter 129: Primary Central Nervous System Lymphoma >
Management and Therapy
Updated By Paul Barr (April 04, 2013) Based on the efficacy of rituximab in non-CNS non-Hodgkin lymphoma, most groups now include the antibody as part of standard treatment. A retrospective single center comparison of chemotherapy with or without IV rituximab suggested a superior response rate and progression free survival for patients ...
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April 04, 2013
Chapter 133: Chronic Myelogenous Leukemia >
Clinical Course and Prognosis
Updated By Michal G. Rose (April 04, 2013) A new risk score, EUTOS, which was developed during the imatinb era, uses the percentage of basophils and the spleen size to identify patients with lower probabilities of responding to therapy and survival. (Hasford J, Baccarani M, Hoffman V, et al. Blood 2011;118:686-92. 21536864 ...
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April 04, 2013
Chapter 133: Chronic Myelogenous Leukemia >
Tyrosine Kinase Inhibitors
Updated By Michal G. Rose (April 04, 2013) These differences have persisted after a median follow-up of 24 months in both studies. (Kantarjian HM, Shah NP, Cortes JE, et al. Blood 2012;119:1123-9. 22160483 ; Kantarjian HM, Hochhaus A, Saglio G, et al. Lancet Oncol 2011;12:841-51. 21856226 )...
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Updated By Michal G. Rose (April 04, 2013) In the BELA trial 502 patients with previously untreated CML were randomized 1:1 to bosutinib 500 mg daily or imatinib 400 mg daily. Complete cytogenetic responses (CCyR) at 12 months, the primary end point of the trial, were not different between the two drugs. However, MMR at 12 months and time to...
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Updated By Michal G. Rose (April 04, 2013) In chronic phase patients resistant to or intolerant of imatinib, 31% achieved major cytogenetic response with bosutinib, (Cortes JE, Kantarjian HM, Brümmendorf TH, et al. Blood 2011;118:4567-76. 21865346 ) and in patients pretreated with imatinib followed by dasatinib and/or ni...
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Updated By Michal G. Rose (April 04, 2013) Among 62 chronic phase patients with the T315I mutation who had failed other tyrosine kinase inhibitors, treatment with subcutaneous omacetaxine resulted in a major hematologic response in 77% of patients and a major cytogenetic response in 23% (Cortes J, Lipton JH, Rea D, et al. Blood 2012;120:257...
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April 04, 2013
Chapter 134: Chronic Lymphocytic Leukemias >
Treatment and Response Criteria
Updated By Michal G. Rose (April 04, 2013) Response rates, median survival, and adverse effects were similar between rituximab-treated, rituximab-refractory, and rituximab-naïve patients. (Wierda WG, Padmanabhan S, Chan GW, et al. Blood 2011;118:5126-29. 21856867 )...
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Updated By Michal G. Rose (April 04, 2013) In a randomized phase 3 trial of previously treated CLL patients, fludarabine plus alemtuzumab prolonged progression free and overall survival, albeit with an increase in serious adverse events in the combination treatment group. (Elter T, Gercheva-Kyuchukova L, Pylylpenko H, et al. Lancet Oncol 201...
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April 04, 2013
Chapter 134: Chronic Lymphocytic Leukemias >
New and Novel Agents for Treatment of Chronic Lymphocytic Leukemia
Updated By Michal G. Rose (April 04, 2013) In a study of 60 symptomatic patients with untreated CLL age 65 years or older, lenalidomide at an initial dose of 5 mg/d and titrated up was well tolerated and resulted in a 65% response rate. (Badoux XC, Keating MJ, Wen S, et al. Blood 2011;118:3489-98. 21725050 )...
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April 04, 2013
Chapter 134: Chronic Lymphocytic Leukemias >
Second Malignancies and Transformation
Updated By Michal G. Rose (April 04, 2013) Therapy-related myeloid neoplasia (myelodysplasia or acute myeloid leukemia) is also a concern in CLL. In long-term follow-up of the US Intergroup Study E2997, 4.7% of patients developed therapy related myeloid neoplasia at a median of 5 years from initial therapy. (Smith MR, Neuberg D, Flinn IW, et...
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April 04, 2013
Chapter 134: Chronic Lymphocytic Leukemias >
Hairy Cell Leukemia
Updated By Michal G. Rose (April 04, 2013) The BRAF V600E mutation was recently found to be present in all patients with hairy cell leukemia, a finding that is likely to have an impact on the diagnosis and possibly the treatment of this disease. (Tiacci E, Trifonov V, Schiavoni G, et al. N Engl J Med 2011;364:2305-15. 21663470 ...
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April 04, 2013
Chapter 134: Chronic Lymphocytic Leukemias >
Molecular Biology
Updated By Michal G. Rose (April 04, 2013) A study of 91 CLL patients using parallel sequencing of DNA from leukemic cells and germline DNA found 9 genes mutated at significant frequencies from 5 core signaling pathways: DNA damage repair and cell cycle control; Notch signaling; inflammatory pathways; Wnt signaling; and RNA splicing and proc...
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April 04, 2013