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The role of radiation therapy (RT) in lung cancer is long established; some of the earliest Radiation Therapy Oncology Group reports dealt with non-small cell lung cancer (NSCLC).[1,2] More recently, the advent of stereotactic body RT (SBRT) techniques has provided significant local control rates after focused treatment of selected small metastases and inoperable early stage lesions.[3,4] Our center has been in the forefront of examining SBRT and its role in central [5] or bilateral [6] lesions, its effect on PET imaging [7] and pulmonary function testing,[8] and subsequent frequency of brachial plexopathy,[9] chest wall toxicity,[10] or pneumonitis.[11] Still, even this highly conformal technique comes with potentially significant dose to adjacent normal tissue. This is in the context of an emerging appreciation for the pulmonary consequences of elevated mean lung dose,[12] or V5 after pneumonectomy.[13] For each lung cancer patient requiring RT, an effective mechanism to deliver dose to the tumor while minimizing dose to uninvolved lung is called for. Enter protons.

Proton radiation for cancer offers the ability to conform the high-dose region of radiation therapy to the tumor while reducing the dose of radiation to adjacent normal tissues. In lung cancer, this equates to greater sparing of uninvolved lung, heart, esophagus, and spinal cord. Sparing these normal tissues permits the delivery of higher-radiation doses to the tumor. Studies that compare the distribution of radiation doses for lung cancer show that proton radiation is superior, even when factors such as respiratory motion are considered. Clinical experience confirms the feasibility of proton radiation for early-stage non-small-cell lung cancers, and clinical trials are being conducted in locally advanced tumors: To date, evidence indicates that proton radiation should be further explored.

Until recently, standard treatment of multiple myeloma (MM) in elderly patients who were not candidates for autologous stem cell transplantation was with the combination of melphalan plus prednisone (MP). Novel agents (thalidomide, lenalidomide, bortezomib) are dramatically changing frontline therapy of MM. Randomized studies have shown the superiority of adding one novel agent to MP, either thalidomide (MPT) or bortezomib (MPV). The combination of lenalidomide with low doses of dexamethasone is another attractive alternative. Recent results show that maintenance therapy with low-dose lenalidomide may prolong progression-free survival. The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. However, toxicity is a significant concern, and doses of thalidomide and of myelotoxic agents should be reduced in patients who are older than 75 years or who have poor performance status. Weekly bortezomib appears to induce severe peripheral neuropathy less frequently than the same agent administered twice weekly. Autologous stem cell transplantation is feasible in selected fit patients over 65 years of age, and its results are improved by the addition of novel agents before and after high-dose therapy. However, considering the progress in non-intensive therapy, autologous transplantation should not currently be offered to elderly patients outside of a clinical trial.

News items reported in this issue: 1) 186-Gene Signature in Cancer Stem Cells Predicts Recurrence 2) National Prostate Cancer Coalition Commences Clinical Trial Education Program 3) Concomitant High-Dose Radiation Therapy Plus Cetuximab Improves Locoregional Control and Reduces Mortality, with No Increase in Radiation Therapy–Associated Toxicity in Patients with Advanced Squamous-Cell Carcinoma of the Head and Neck 4) STAT3 Pathway Inhibitor (Degrasyn) Drug Class Shows Promise in the Treatment of Malignant Brain Tumors

News items reported in this issue: 1) 186-Gene Signature in Cancer Stem Cells Predicts Recurrence 2) National Prostate Cancer Coalition Commences Clinical Trial Education Program 3) Concomitant High-Dose Radiation Therapy Plus Cetuximab Improves Locoregional Control and Reduces Mortality, with No Increase in Radiation Therapy%u2013Associated Toxicity in Patients with Advanced Squamous-Cell Carcinoma of the Head and Neck, and more

Primary surgery with an abdominoperineal resection (APR) was historically the standard of care for localized anal squamous cell carcinoma. APR achieved 40%-70% survival rates at five years, with local failures from 27%-47%.[1,2] With modern technology and radiation dose escalation, external beam radiation therapy (EBRT) studies have improved complete response rates, decreased morbidity, and improved sphincter preservation rates. Nigro et al added 5-fluorouracil (5FU) and mitomycin C (MMC) to concurrent EBRT [3,4] and impressive complete response rates inspired other groups to investigate the role of chemotherapy as a component of sphincter-preserving therapy. The European Organization for Research and Treatment of Cancer (EORTC) and United Kingdom Coordinating Committee on Cancer Research (UKCCCR) studies reported improved local control and colostomy-free survival when chemotherapy (5FU/MMC) was administered in conjunction with radiation.[5,6] The five-year survival rate for patients receiving standard chemoradiation approaches 70%; however, 20%-40% experience grade 3-4 toxicity, and administration with MMC causes profound hematologic toxicity.

The Clinical Trials reported in this issue include: PHASE I: 1) Cell Genesys and Medarex Remain Positive on Combination Immunotherapy Study 2) Active Biotech Achieves Success with TASQ for Prostate Cancer PHASE II: 1) Myriad Initiates Evaluation of Brain Cancer Drug that Crosses the Blood-Brain Barrier 2) Second Lung Cancer Trial Adds Data to Novel Therapy PHASE III: 1) Nexavar Could Soon Add Primary Liver Cancer to its Label 2) Point Therapeutics Provides Clinical Update for NSCLC Studies

A preclinical study provides the rationale for combining BRAF-targeted therapy with immunotherapy agents in patients with BRAF mutations. These mutations activate the MAPK signaling pathway, which leads to increased oncogenic potential. The researchers showed that in BRAF-mutant melanoma cell lines, a selective BRAF inhibitor (PLX4720) blocked the MAPK pathway and increased tumor antigen expression without affecting T-cell function.

Physicians' Financial News focuses on newsmaking and/or notable companies in the oncology/biotech sector. In this issue: 1) Pharmion: Oncology-Centered Focus Fuels Continued Pharmion Growth 2) Bristol-Myers Squibb: Treatment-Resistant Breast Cancer Targeted 3) Merger-Mania Poised to Envelop Biotech Sector? 4) GlaxoSmithKline: Oral Therapy Option Offered for Small-Cell Lung Cancer Relapse 5) Immunomedics,Inc.: Immunomedics Wins Pancreatic Cancer Patent 6) ZymoGenetics: Promising Kidney Cancer Therapy Moves Toward Phase II

Topics covered in this issue include:1) Dosing Patterns and Costs of Erythropoesis-Stimulating Agents in Patients With Cancer2) New Practice Guideline Updates Treatment of Nonâ%uFFFD%uFFFDSmall Cell Lung Cancer3) Large Health Insurer Begins Genetic Risk Counseling for Cancer4) Multiple Myeloma Guidelines Now Include Combination Therapy With Bortezomib5) Survey Finds That Managed Car Executives Are Misinformed About the Value and Cost of Cancer Biologics

The Clinical Trials reported in this issue include: PHASE III: 1) What Factors Predict Prognosis in Patients With Malignant Pleural Mesothelioma? 2) Treatment for Patients With High-Risk Postoperative Breast Cancer PHASE II: 1) Epratuzumab Plus Rituximab Equals Non-Hodgkin's Lymphoma Response 2) Topotecan Added to Twice-Daily Chemoradiation to Treat Limited- Stage, Small-Cell Lung Cancer 3) First-Line Therapy for Patients With Advanced or Metastatic Non–Small-Cell Lung Cancer 4) Radiotherapy for Nasal Squamous Cell Carcinoma Therapy PHASE I/II: 1) A New Combination Approach for Advanced-Stage Germ-Cell Tumors

Articles in this issue include: 1) South Korea: Is Intermittent Imatinib Therapy for Chronic Myelogenous Leukemia an Option? Genetic Marker Predicts Treatment Resistance and Poor Outcomes in Esophageal Cancer 2) France: Pelvic Radiation in Addition to Prostate Radiotherapy for Localized Prostate Cancer 3) Multiple Sites in Europe: European Guidelines for Oral Mucositis Released 4) Japan: The Care of Delirium in Terminal Illness and Bereavement Needs 5) The Netherlands: Cancer Pain and Adherence to Analgesic Treatment 6) Switzerland, Belgium & France: Confirmation of Gene Expression Link to Chemotherapy Response in Breast Cancer

Clinical Trial Reports in this issue include: Phase IV: 1) Long-Term Aspirin Therapy Reduces Colorectal Cancer Risk Phase III: 1) Does Adding Cisplatin to Adjuvant Chemotherapy Improve Outcomes in Advanced Gastric Cancer? 2) FOLFIRI Plus Bevacizumab Provides Better Survival Than Other Irinotecan-Containing Regimen in First-Line Colorectal Cancer Phase II: 1) Single-Agent Activity of Sunitinib in Refractory Non������¢���¯���¿���½���¯���¿���½Small Cell Lung Cancer 2) The Importance of Targeting Androgen Receptor Signaling for Prostate Cancer Response Rate 3) Improving Survival in Gastrointestinal Stromal Tumor 4) Improving Overall Survival in Patients With Hormone- Resistant Prostate Cancer 5) Breast Cancer Stem Cells Decreased With Neoadjuvant Lapatinib Phase I/II: 1) Patients With Recurrent Glioblastoma May Benefit From Implant Combinations

Phase IV:1) Cancer Risks and Postmenopausal Hormone Link ConfirmedPhase III:1) Do Vitamins Protect Against Lung Cancer?2) Longer Life Expectancy in Pancreatic Cancer When Gemcitabine Is Added to Chemotherapy3) Outcomes Improve With Letrozole Treatment in Women With Early-Stage Breast Cancer4. Pemetrexed vs. Docetaxel for Non-Small Cell Lung Cancer TreatmentPhase II:1) Talactoferrin-Alfa Treatment for Non-Small Cell Lung Cancer2) Advanced Carcinoid Systemic Therapy

Phase IV: 1) Cancer Risks and Postmenopausal Hormone Link Confirmed Phase III: 1) Do Vitamins Protect Against Lung Cancer? 2) Longer Life Expectancy in Pancreatic Cancer When Gemcitabine Is Added to Chemotherapy 3) Outcomes Improve With Letrozole Treatment in Women With Early-Stage Breast Cancer 4. Pemetrexed vs. Docetaxel for Non-Small Cell Lung Cancer Treatment Phase II: 1) Talactoferrin-Alfa Treatment for Non-Small Cell Lung Cancer 2) Advanced Carcinoid Systemic Therapy

T umor human papillomavirus (HPV) status is confirmed as a strong and independent prognostic factor for survival of patients with oropharyngeal cancer, report investigators for a large phase III trial established by the Radiation Therapy Oncology Group. Results were presented at the 44th annual meeting of the American Society of Clinical Oncology (ASCO abstract 5510) and published in the New England Journal of Medicine on June 7. Investigators performed a retrospective analysis of the association between tumor HPV status and survival among 323 patients with stage III or IV oropharyngeal squamous cell carcinoma who were enrolled in a randomized trial comparing cisplatin therapy combined with either accelerated- or standard-fractionation radiotherapy. Risk of death among patients with HPV-positive vs HPV-negative cancer was compared using a proportional-hazards model.

Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is a low-grade cutaneous lymphoma characterized by skin-homing CD4+ T cells. It is notable for highly symptomatic progressive skin lesions, including patches, plaques, tumors, and erytheroderma, and has a poorer prognosis at later stages. Diagnosis remains difficult owing to MF’s nonspecific skin presentation and identification of the optimal treatment strategy is challenging given the paucity of controlled trials and numerous and emerging treatment options. Management includes topical therapy with the addition of systemic therapy for patients with later-stage disease including tumors; erythroderma; and nodal, visceral, or blood involvement. Topical therapies include mechlorethamine (nitrogen mustard), carmustine (BCNU), steroids, bexarotene gel (Targretin Gel), psoralen plus ultraviolet A (PUVA), ultraviolet B (UVB), and either localized or total skin electron radiotherapy. Systemic therapies include interferon, retinoids, oral bexarotene (Targretin), denileukin diftitox (Ontak), vorinostat (Zolinza), extracorporeal photochemotherapy (photopheresis), and cytotoxic chemotherapy. Herein, we outline clinically relevant aspects of MF, including clinical presentation, pathology, diagnosis, and staging. We describe in detail existing and emerging therapeutics and offer specific recommendations for management of each stage of MF.

The review by Oxnard and Miller provides a thoughtful update on the use of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib (Iressa) and erlotinib (Tarceva) as front-line therapy in patients with non–small-cell lung cancer (NSCLC).

With better disease definition, staging, and monitoring, treatment of extranodal NK/T-cell lymphoma is becoming more rational. A large proportion of patients with localized nasal disease may enjoy prolonged disease-free survival. On the other hand, early HSCT or novel therapy may be recommended for aggressive extranasal disease.