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Commentary (Droller): Prostate-Specific Antigen as a Marker of Disease Activity in Prostate CancerThis second installment on prostate specific antigen (PSA) as a marker of disease activity and cancer cell viability in prostate cancer focuses on its role in monitoring the effects of a variety of therapies at different stages of the disease. In addition, the authors propose guidelines for studying the efficacy of new treatments in this setting.
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Hypofractionation for Breast Cancer: Lessons Learned From Our Neighbors to the North and Across the PondIn this review we discuss the rationale and underlying radiobiologic concepts for hypofractionation, and review the clinical trials and ASTRO guidelines supporting hypofractionated radiation in the treatment of breast cancer.
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Quick Reference for Oncology CliniciansAs a midcareer academic medical oncologist, I have found that some books are especially useful as a pocket reference. Some books are small enough for a briefcase, but not ideal for a coat pocket. Others are best sequestered on a bookshelf. Where a book is placed often influences how one will (or won't) use it or read it.
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Principles of Radiation TherapyThis chapter provides a brief overview of the principles of radiation therapy. The topics to be discussed include the physical aspects of how radiation works (ionization, radiation interactions) and how it is delivered (treatment machines, treatment planning, and brachytherapy).
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Concurrent Chemotherapy and Radiotherapy in Patients With Brain TumorsBecause treatment for most brain tumors remains inadequate, there has been a sustained interest in using concurrent chemotherapy and radiotherapy to improve local control, prolong overall survival, and reduce
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Transoral Robotic Surgery (TORS): The Natural Evolution of Endoscopic Head and Neck SurgeryThe article presented by Bhayani, Holsinger, and Lai thoroughly evaluates the emergence of transoral robotic surgery (TORS) as a technique in the field of otolaryngology. Transoral approaches to the upper aerodigestive tract, whether for diagnostic or therapeutic purposes, represent core tenets of the discipline and formed one of the bases for the inception of the specialty. Innovations and refinements in optics and materials have steadily increased the view, reach, and, consequently the effectiveness of the endoscopic surgeon with each passing decade. In the past thirty years, the introduction of the laser has further enhanced the capabilities of the surgeon, augmenting treatment options beyond open tumor resection and chemoradiation. The introduction of the daVinci robot is an incremental step in the development of techniques that have been evolving over the past one hundred and twenty years.
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Managing CLL: A New Level of SophisticationFor decades, initial therapy for chronic lymphocytic leukemia (CLL) consisted of alkylators such as chlorambucil (Leukeran). The introduction of nucleoside analogs such as fludarabine and monoclonal antibodies such as rituximab (Rituxan) markedly changed the initial therapy of CLL, particularly in the United States. Fludarabine and combination regimens such as fludarabine/cyclophosphamide (FC) have achieved higher complete response (CR) rates and progression-free survival (PFS) than chlorambucil in previously untreated CLL, but long-term overall survival has not improved, due to concurrent improvement in salvage therapy of relapsed CLL patients. Upfront chemoimmunotherapy regimens such as fludarabine/rituximab (FR) and fludarabine/cyclophosphamide/rituximab (FCR) have similarly improved CR rates and PFS in previously untreated CLL patients, but it is unclear whether overall survival is improved. Advances in cytogenetic analysis and other biologic prognostic factors have greatly enhanced clinicians' ability to risk-stratify newly diagnosed CLL patients, and knowledge of such prognostic factors is necessary to properly interpret results of clinical treatment studies. The choice of initial therapy for an individual patient should depend upon the patient's age and medical condition, cytogenetic and other prognostic factors, and whether the goal of therapy is maximization of CR and PFS or palliation of symptoms with minimal toxicity.
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Lung Cancer Management in 2010Exciting advances in understanding the biology of lung cancer have occurred over the last few years.
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Endoscopic Ultrasound in the Diagnosis and Staging of Pancreatic CancerPatients with signs and symptoms suggestive of a pancreatic neoplasm typically undergo initial imaging with transabdominal ultrasound or computed tomography. This evaluation often reveals the presence of a pancreatic mass or fullness.
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Smaller Incisions for Smaller CancersSmaller early-stage tumors may lend themselves to less radical lung parenchymal sparing resections or no surgery at all.
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Commentary (Mastrangelo/Berd): Systemic Treatments for Advanced Cutaneous MelanomaAnderson and colleagues present a comprehensive and factually accurate overview of systemic treatment for advanced melanoma. They correctly identify dacarbazine as the only single agent officially sanctioned for the treatment of metastatic melanoma. They further opine that "dacarbazine alone remains the standard of care for initial chemotherapy treatment of metastatic melanoma." With overall response rates of 10% to 20%, a complete response rate of less than 4%, and no evidence that treatment with dacarbazine improves survival over best palliative care, one questions whether or not dacarbazine would merit approval if reevaluated today.
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Michael J. Morris, MD, on Future Directions of PSMA Imaging in Prostate CancerResults of phase 3 CONDOR study could have a far-reaching impact on patients with prostate cancer.
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The Economics of Prostate Cancer ScreeningThe introduction of prostate-specific antigen (PSA) testing for use in the early detection of prostate cancer has led to controversy regarding the appropriateness of prostate cancer screening and any subsequent treatment. Much
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Current Status of Adjuvant Therapy for Colorectal CancerAdjuvant therapy with chemotherapy and/or radiation therapy inaddition to surgery improves outcome for patients with high-risk carcinomasof the colon or rectum. For colon cancer, fluorouracil (5-FU)combined with leucovorin is a current standard of care that improveslong-term survival. A recent European trial (MOSAIC) has documentedsignificant improvement in 3-year disease-free survival when oxaliplatin(Eloxatin) was added to infusional 5-FU and leucovorin in the FOLFOXregimen. Two US cooperative group trials will evaluate the addition ofantiangiogenesis therapy with bevacizumab (Avastin) to chemotherapy.A third trial will evaluate FOLFOX, irinotecan (Camptosar) combinedwith infusional 5-FU and leucovorin (FOLFIRI), and the sequentialuse of FOLFOX followed by FOLFIRI. In rectal cancer, postoperative5-FU–based chemotherapy combined with irradiation can improve bothlocal tumor control and survival. The German Rectal Cancer Grouphas recently reported that preoperative combined-modality therapy isless toxic and more effective in preventing local tumor relapse comparedto similar treatment given postoperatively. A coordinated pair ofcooperative group clinical trials will evaluate oral capecitabine (Xeloda)as a radiation enhancer in the preoperative setting, and the FOLFOXand FOLFIRI regimens compared to 5-FU and leucovorin followingsurgery. Predictive and prognostic molecular markers will be studiedin these new adjuvant therapy clinical trials for both colon and rectalcancer with the goal of developing future regimens tailored to individualpatients. There has been a recent and dramatic increase in thepace of drug development for colorectal cancer which holds promise tofurther improve curative therapy as part of a multidisciplinary approachin the surgical adjuvant setting.
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CLM in GALAXY: MRD Predicts Adjuvant Therapy Benefit and PrognosisPanelists discuss how minimal residual disease (MRD) detection in patients with colorectal liver metastases (CLM) in the GALAXY study predicts both the benefit of adjuvant therapy and overall prognosis, potentially guiding more personalized treatment decisions.
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Transanal Excision of Rectal Cancer: A Work in ProgressThe exact role of combined-modality therapy and TAE of rectal cancer remains to be defined. Certainly the stakes are high, as studies have shown that the recurrence of locally excised rectal cancer is associated with worse long-term survival outcomes.
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Salvage Brachytherapy After External-Beam Irradiation for Prostate CancerDr. Beyer provides an insightful and balanced approach tothe indications for salvageprostate brachytherapy after externalbeamradiotherapy failure. As hepoints out, the challenge for the cliniciancontemplating local salvage therapyto address biochemical failure isto determine whether the biochemicalrelapse represents local relapse onlyor systemic disease. Local salvagetreatment in a patient with micrometastaticdisease would have no appreciableimpact on disease-free survivaland is more likely to be associatedwith significant potential morbidity.Unfortunately, with the current lackof reliable molecular markers or sensitiveimaging modalities, it is impossibleto determine with certainty thesource of a biochemical relapse inmost settings.
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Langerhans Cell Histiocytosis Enters the Genomics AgeThis increased understanding of the pathophysiology of Langerhans cell histiocytosis should help guide treatment and therapies and provides the rationale for using agents effective against myeloid malignancies.
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The Prostate Cancer Intervention Versus Observation Trial (PIVOT)The Prostate Cancer Intervention Versus Observation Trial (PIVOT) is a randomized trial designed to determine whether radical prostatectomy or expectant management provides superior length and quality of life for men with clinically localized prostate cancer. Conducted at Department of Veterans Affairs and National Cancer Institute medical centers, PIVOT will enroll over 1,000 individuals less than 75 years of age. The primary study end point is all-cause mortality. Secondary outcomes include prostate cancer- and treatment-specific morbidity and mortality, health status, predictors of disease-specific outcomes, and cost-effectiveness. Within the first 3 years of enrollment, over 400 men have been randomized. Early analysis of participants' baseline characteristics indicate that enrollees are representative of men diagnosed with clinically localized prostate cancer throughout the United States. Therefore, results of PIVOT will be generalizable. These results are necessary in order to determine the preferred therapy for clinically localized prostate cancer. [ONCOLOGY 11(8):1133-1143, 1997]
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Targeted Therapy: an Evolving Concept in Esophageal AdenocarcinomaEsophageal adenocarcinoma (EAC) affects approximately 11,000 persons per year in the United States, is increasing in incidence, and is associated with an exceptionally high mortality rate.[1-4] In this issue of ONCOLOGY, Krasna reviews the role of multimodality therapy in the treatment of EAC. Poor outcome in patients with EAC is reflective of both deficiencies in early detection and the inadequacy of available therapies across stages.
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Weighing the Evidence for Immune Therapy and Targeted Therapy in Renal Cancer and MelanomaUltimately, as agents in both VEGF-targeted and immunotherapy classes with lower toxicity rates are developed, questions of combination and sequence will inspire clinical investigations of strategies that, it is hoped, will maximize both the quantity and quality of life for patients with RCC. Melanoma therapy drug development continues to lead the way with regard to what is therapeutically possible with immunotherapy-and suggests that HD IL-2 continues to be relevant in today’s treatment landscape.
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Sharp Rise in Mastectomy in Early-Stage Breast CancerA retrospective cohort study of women treated for early-stage breast cancer has confirmed rising trends in the proportion of patients who undergo mastectomy.
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Cancer Care and Accountable Care Organizations: The Unknown Patient Experience LandscapeACOs can provide the structure, but it’s up to the stakeholders to establish mutually agreeable goals for this new care delivery model. Achieving these goals will require a different set of dialogues and conversations among stakeholders, and patients and their advocates must have seats at the table.
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Infusional 5-FU, Folinic Acid, Paclitaxel, and Cisplatin for MetastaticOur phase II study results demonstrating high efficacy and low toxicity for a weekly schedule of high-dose, 24-hour infusional 5-fluorouracil(5-FU)/folinic acid (HD5-FU/FA) in intensively pretreated patients with metastatic
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Cervical Cancer: Issues of Sexuality and FertilityCervical cancer rates have fallen in the United States; regardless, thedisease remains a significant concern for women, especially those whoare premenopausal. The management of cervical cancer is dependenton stage of disease at diagnosis, and specific needs emerge for patientsboth during and following treatment. Over the past decade, the focus hasbeen to maintain adequate tumor control while reducing long-termnegative consequences. However, problems with sexuality and fertilitypersist for women treated for cervical cancer despite these advances.Sexual dysfunction following treatment for gynecologic cancer hasbeen well documented in the literature, and recent studies demonstratethe success of brief psychosexual interventions. Treatment of sexualdifficulties in cancer patients can be achieved through the provision ofinformation, support, and symptom management, ideally as part of asexual health program. Resources are not always available to developsuch a program. However, medical professionals can identify individualsand organizations with expertise in treating sexual and fertilityconcerns, which can be provided to their patients, making help withthese problems more accessible as needs arise.
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Morbidity of Contemporary Radical Retropubic Prostatectomy for Localized Prostate CancerComplication rates in 1,000 consecutive patients who underwent radical retropubic prostatectomy for clinically localized prostate cancer between November 1989 and January 1992 were assessed and compared to complication rates in a historical group of patients operated on by primarily the same surgeons prior to 1987. In the contemporary series, there were no operative deaths, only 22% of patients required blood transfusion, and only six (0.6%) patients suffered rectal injuries. Early complications, including myocardial infarction, pulmonary embolism, bacteremia, and wound infection, occurred in less than 1% of patients. Vesical neck contracture, the most common late complication, developed in 87 patients (8.7%). At 1 year post-surgery, 80% of patients were completely continent, and fewer than 1% were totally incontinent. [ONCOLOGY 9(5):379-389, 1995]
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Systemic Approaches for Multifocal Bronchioloalveolar Carcinoma: Is There an Appropriate Target?Bronchioloalveolar carcinoma (BAC) is a subset of pulmonary adenocarcinoma characterized by distinct and unique pathological, molecular, radiographic, and clinical features. While the incidence of pure BAC is rare, comprising only 1% to 4% of non–small-cell lung cancer (NSCLC), mixed subtypes (including BAC with focal invasion and adenocarcinoma with BAC features) represent as much as 20% of adenocarcinomas-and that figure may be increasing. Despite the longstanding recognition of this entity, there is no established treatment paradigm for patients with multifocal BAC, resulting in competing approaches and treatment controversies. Current options for multifocal BAC include both surgery and systemic therapies. Unfortunately, prospective data on systemic approaches are limited by study design and small patient numbers; there are only seven phase II studies involving four therapies. This article evaluates key characteristics of BAC, including the current understanding of histopathology and tumor biology. In addition, it comprehensively reviews the systemic phase II studies in an attempt to clarify the therapeutic challenges in this disease. It also includes the first proposed treatment paradigm that integrates both EGFR mutational status and the sub-histologies, mucinous and nonmucinous BAC.
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Endoscopic Diagnosis and Management of Gastrointestinal MalignancyThe endoscopic diagnosis, staging, and therapy of gastrointestinal (GI) malignancies has advanced rapidly and dramatically over the past 15 years. Video-endoscopy has generally replaced fiberoptic endoscopy, and the digitally based fidelity, sharper resolution, and improved magnification of the video-endoscopic image offers a potentially better approach for the evaluation of mucosal abnormalities.
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Thromboembolic Complications of Malignancy: Part 2Thromboembolism affects many patients with solid tumors and clonalhematologic malignancies. Thromboprophylaxis with low-molecularweightheparin (LMWH) is indicated for surgery and other high-risksituations, but not routinely for central venous catheters or nonsurgical,ambulatory management. Thrombotic events require full anticoagulationfor the duration of active disease and/or the prothromboticstimulus. LMWHs are safe and more effective than both unfractionatedheparin for initial therapy and warfarin for secondary prevention. Antiinflammatoryand antiangiogenic properties might account for thisadvantage and for a survival benefit of chronic LMWH in subgroupsof cancer patients. Ongoing studies are characterizing the cost-effectivenessand antitumor mechanisms of LMWHs, the potential utility ofnewer anticoagulants, and the ability of predictive models to identifyhigh-risk candidates for thromboprophylaxis.
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Commentary (Meyers): Systemic Treatments for Advanced Cutaneous MelanomaThe history of systemic treatments for advanced cutaneous melanoma, which is reviewed thoroughly in the paper by Anderson et al, can best be characterized as a series of unrealized hopes.
