Authors

Monitoring Changes in the Microenvironment During Targeted Therapies

This review covers progress to date in the identification of molecular targets on blood vessels in cancers, as well as agents that act on those targets, with emphasis on those currently in clinical trials. Current vascular-targeting therapies comprise two general types—antiangiogenic therapy and antivascular therapy. Advances in antiangiogenic therapies, particularly inhibitors of vascular endothelial growth factors and their receptors, have clarified the capacity of these inhibitors to change tumor-associated vessel structure to a more normal state, thereby improving the ability of chemotherapeutics to access the tumors. The responses of other antiangiogenesis target molecules in humans are more complicated; for example, αvβ3 integrins are known to stimulate as well as inhibit angiogenesis, and cleavage of various extracellular proteins/proteoglycans by matrix metalloproteinases produces potent regulators of the angiogenic process. Antivascular therapies disrupt established blood vessels in solid tumors and often involve the use of ligand-based or small-molecule agents. Ligand-based agents, irrespective of the antiangiogenic capacity of the ligand, target antivascular effectors to molecules expressed specifically on blood vessels, such as aminopeptidase N, fibronectin extra-domain B, and prostate-specific membrane antigen. Small-molecule antivascular agents, which are not targeted to molecules on blood vessels, rely on physical differences between the vasculatures in tumors and those in normal tissues.

Prophylactic Cranial Irradiation for Patients With Locally Advanced Non–Small-Cell Lung Cancer

Prophylactic cranial irradiation(PCI) in patients with locallyadvanced non–small-cell lungcancer (NSCLC) remains an area ofcontroversy. Dr. Gore has provided areview of the literature, including randomizedand nonrandomized studiesand, in particular, the ongoing RadiationTherapy Oncology Group trial(RTOG 0214), which is randomizingNSCLC patients to PCI or observation.

Non-Secretory Myeloma: One, Two, or More Entities?

To define the differences between the subtypes of myeloma patients, not only prospective collection of clinical and laboratory data are needed, but also cytogenetics and molecular profiling.

Can We Know What to Do When DCIS Is Diagnosed?

It is ironic that while huge strides have been made in the treatment of invasive breast carcinoma, resulting in breast conservation for many women, the most appropriate treatment of noninvasive breast carcinoma remains a topic of hot debate.

Irinotecan in the Management of Patients With Pancreatic Cancer

Synergy with no overlapping toxicities has been demonstrated for the combination of irinotecan ( Camptosar, CPT-11) and gemcitabine (Gemzar) in vitro. Results of a single-institution phase I study in which patients with

Exercise Improves Aromatase Inhibitor-Associated Joint Pain in Breast Cancer Survivors

11 Phase 3 Study of Neoadjuvant Pembrolizumab or Placebo Plus Chemotherapy, Followed by Adjuvant Pembrolizumab or Placebo Plus Endocrine Therapy for Early-Stage High-Risk ER+/HER2– Breast Cancer: KEYNOTE-756

Advances in the Systemic Treatment of Metastatic Melanoma

Within the relatively short time that ipilimumab and vemurafenib have been commercially available, phase II data for the investigational agents nivolumab and MK-3475, for the combination of dabrafenib and trametinib, and for adoptive cell therapy strongly suggest even further improvements in treatment outcomes.

Neoadjuvant Therapy for Early-Stage Breast Cancer: Current Practice, Controversies, and Future Directions

In this review, we will discuss multidisciplinary considerations in treating patients with neoadjuvant therapy and highlight areas of controversy and ongoing research.

Hereditary Breast and Ovarian Cancer: High-Risk Management

The patient, DB, is a 51-year-old white, married female with a strong family history of breast cancer. She presented for high-risk assessment and genetic testing following the discovery of a deleterious mutation in a family member.

Osteoporosis, Fractures, and Risk of Falls

Osteoporosis in elderly cancer patients is an increasing problem, yet it remains under-recognized and under-managed. We commend Dr. Balducci for writing a comprehensive review of the bone complications associated with cancer and its treatment in the elderly.

Management of the Clinically Node-Negative Axilla: What Have We Learned From the Clinical Trials?

Here we review the evolution of sentinel lymph node biopsy for the management of clinically node-negative breast cancer, and we address the current controversies and management issues.

Management of Anal Cancer in the HIV-Positive Population

Squamous cell anal cancer remains an uncommon entity; however,the incidence appears to be increasing in at-risk populations, especiallythose infected with human papillomavirus (HPV) and human immunodeficiencyvirus (HIV). Given the ability to cure this cancer using synchronouschemoradiotherapy, management practices of this disease arecritical. This article considers treatment strategies for HIV-positive patientswith anal cancer, including the impact on chemoradiation-inducedtoxicities and the role of highly active antiretroviral therapy in the treatmentof this patient population. The standard treatment has beenfluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agentsplus radiation. Consideration to modifying the standard treatment regimeis based on the fact that patients with HIV tend to experience greatertoxicity, especially when CD4 counts are below 200; these patients alsorequire longer treatment breaks. Additional changes to the chemotherapydosing, such as giving 5-FU continuously and decreasing mitomycin dose,are evaluated and considered in relation to radiation field sizes in an effortto reduce toxicity, maintain local tumor control, and limit need forcolostomy. The opportunity for decreasing the radiation field size andusing intensity-modulated radiation therapy (IMRT) is also considered,particularly in light of the fact that IMRT provides dose-sparing whilemaximizing target volume dose to involved areas. The impact of the immunesystem in patients with HIV and squamous cell carcinoma of theanus and the associated response to therapy remains unknown. Continuedstudies and phase III trials will be needed to test new treatment strategiesin HIV-infected patients with squamous cell cancer of the anus todetermine which treatment protocols provide the greatest benefits.

About This Treatment Guide

The Oncology Group, a division of CMPMedica, publisher of the journal ONCOLOGY and the news magazine Oncology News International, as well as the comprehensive cancer website, cancernetwork.com, is pleased to bring you the 10th annual edition of Cancer Management: A Multidisciplinary Approach.

The Challenge of Palliating Pancreatic Cancer

FDA approval of palliative chemotherapy is largely based on disease-free and overall survival, quality of life, and symptom reduction; the latter should be routinely measured by the treating oncologist. Physician assessments of symptoms underreport symptom severity compared to patient-reported symptom assessments.

Transplant Registries: Guiding Clinical Decisions and Improving Outcomes

About 50,000 hematopoietic stem cell transplantations are performed yearly, primarily for malignancies. Use of this therapy increased dramatically over the past 30 years due to its proven and potential efficacy in diverse

Commentary (Thomas/Greco): Myalgias and Arthralgias Associated With Paclitaxel

Despite nearly a decade of paclitaxel’scommercial availability,the best strategy formanaging several paclitaxel-relatedtoxicities including myalgia/arthralgiaremains to be elucidated. Mostavailable data in the treatment of myalgia/arthralgia have been anecdotal,reported in the form of case studiesor within the toxicity results of publishedpaclitaxel-containing clinicaltrials. Garrison et al have provided awell-written review summarizingwhat is currently known about theincidence and management of thisquality-of-life–impacting toxicity.

HER2-Directed Treatment of Metastatic Breast Cancer: Unanswered Questions

As more drugs become available in the HER2 arena, clinicians will be faced with increasing challenges regarding which sequences and combinations of drugs will be the best for their patients. In the era in which we practice, a great deal of this is likely to be dictated by the payers.

End Results of Salvage Therapy After Failure of Breast-Conservation Surgery

Lannin and Haffty provide aninteresting and informative reviewon the management andclinical course of an ipsilateral breasttumor recurrence (IBTR) followinglumpectomy and breast irradiation forprimary breast cancer. They presentan engaging discussion concerningthe distinction of a true recurrencefrom a new primary tumor within theipsilateral breast. Although bothevents are included in the term IBTR,the authors point out that the morefavorable outcome follows treatmentof a new primary as opposed to a truerecurrence. Presumably, the true recurrencewould indicate tumor thathas not been eradicated by surgeryand radiotherapy (with or without systemictherapy), which would be amore aggressive malignancy. Thebetter prognosis for a new primarynotwithstanding, there is still a lackof data to indicate whether treatmentshould be different for these twoentities.

Van Nuys Experience Contradicts NSABP B-17 Findings

In the May, 1997, issue of Oncology News International , the updated eight-year results of NSABP protocol B-17 were reported as presented by Dr. Bernard Fisher in Paris. B-17 randomized patients with ductal carcinoma in situ (DCIS) into two groups: One group received excision only, the other excision plus postoperative radiation therapy.

Surgical Treatment of Metastatic Pulmonary Soft-Tissue Sarcoma

The lung is the most frequent site of metastasis from soft-tissue sarcomas. Due to the relative resistance of sarcoma to either chemotherapy or radiotherapy, compared to other solid tumors, surgical management of

Commentary (Sendowski/Segal): Management of Health-Care–Associated Infections in the Oncology Patient

Infections are major causes of morbidityand mortality in patientswith cancer. In certain instances,the malignancy itself can predisposepatients to severe or recurrent infections.For example, acute leukemiamay cause neutropenia and ensuingbacterial or fungal infection. Hypogammaglobulinemiaof chroniclymphocytic leukemia may be complicatedby infections due to encapsulatedbacteria. Patients withHodgkin’s lymphoma may sufferfrom recurrent varicella-zoster infections.Solid tumors may obstruct thelumens of respiratory, digestive, andurinary tracts, leading to bacterial infections.Nevertheless, the principalrisk of infectious complications is relatedto the intensity and duration ofimmunosuppressive chemotherapy.Patients with cancer constitute ahighly varied population, both interms of the underlying malignancyand in terms of their immunosuppression.In addition, a single patientmay have multiple predisposing factors,thus increasing the spectrum oflikely pathogens. When evaluating apatient with cancer for a possible infection,it is essential to develop aconceptual framework of quantitativeand qualitative immune defectsthe patient is likely to have, and thento stratify the risk for specific pathogensin the context of the history,physical exam, and laboratorydata.[1]

Screening for Ovarian Cancer: What We Know, What We Need to Know

The majority of women with ovarian cancer present with advanced-stage disease. Women with early-stage ovarian cancer have a much better chance of achieving a cure than do women with late-stage disease. This

A Newly Discovered Liver Mass in a 65-Year-Old Woman

A 65-year-old woman with rheumatoid arthritis and autoimmune hepatitis presented to clinic for evaluation of a liver mass. Six months prior to presentation, workup was initiated for elevated liver enzyme levels.

COUNTERPOINT: Surgical Management of Lymph Node Basin in Sentinel Lymph Node–Positive Melanoma

Ironically, the patients who can benefit the most from CLND in terms of regional nodal basin disease control are the patients who are least likely to experience a survival benefit.

Mantle Cell Lymphoma: Clinicopathologic Features and Treatments

Mantle cell lymphoma (MCL) accounts for approximately 6% of non-Hodgkin’s lymphomas. Patients usually present with advanced disease, with a tendency for extranodal involvement. MCL is an aggressive lymphoma with moderate chemosensitivity, but it remains one of the most difficult therapeutic challenges. Complete response rates to chemotherapy range from 20% to 40%, with median survivals of 2½ to 3 years. Anthracycline-containing regimens do not prolong survival compared with nonanthracycline regimens. Single-agent rituximab (Rituxan) has produced response rates of about 30%, and when combined with an anthracycline-containing regimen, response rates increase to above 90%; however, an impact on survival has not yet been demonstrated. More intensive regimens such as hyperCVAD (hyperfractionated cyclophosphamide [Cytoxan, Neosar], vincristine, doxorubicin [Adriamycin], dexamethasone, methotrexate, cytarabine) with either stem cell transplant or rituximab have been associated with promising results.

Salvage Therapy for Ovarian Cancer

As Drs. Sabbatini and Spriggs point out in their review, the majority of ovarian cancer patients continue to present with advanced-stage disease, and only a minority are cured after primary surgery and chemotherapy. At present, recurrent disease is best viewed as a chronic illness that requires ongoing management. A number of therapeutic options are available, but opportunities for cure remain limited. My comments will focus on post-remission therapy, small-volume residual disease, intraperitoneal therapy, secondary cytoreductive surgery, choice of second-line chemotherapy, and participation in phase II studies.

Leveraging Surgical Oncology to Treat Gastrointestinal Cancers

“The pendulum is moving fast towards giving chemotherapy prior to surgery, and the research is going on to continue that trend.”

Commentary (Danso, Seidman): Trastuzumab in Breast Cancer

The clinical development of trastuzumab(Herceptin) for thetreatment of HER2-overexpressingbreast cancer has been perhapsthe most important recentadvance in the management of metastaticbreast cancer. In their rigorousand comprehensive review, Emensand Davidson highlight the importanttrials that resulted in the US Food andDrug Administration (FDA) approvalof trastuzumab, discuss combinationchemotherapy options with trastuzumab,and preview promising futurestrategies for combining trastuzumabwith other targeted biologic agents.

Where Expert Opinion Meets Public Resistance

There is concern and growing evidence that the supply of medical oncologists in the United States will be insufficient to meet the needs of future patients. With an aging population and increasing complexity of cancer therapies, it is clear there will be more patients and that they will live longer and require expert care. It is equally clear that the number of specialists trained in cancer medicine is not growing fast enough to meet projected needs, so new models of care will need to be designed and implemented. Innovation in practice models will require the integration of non-physician practitioners (nurse practitioners and physician assistants) into multidisciplinary teams, broader use of technology to allow virtual consultations and the secure exchange of vital health information, increased utilization of community services, and public acceptance.