ONCOLOGY Vol 19 No 7

Drs. Chandler and Silva providean excellent review ofthe technical aspects of tumorextirpation in their article, “ExtendedTransbasal Approach to Skull BaseTumors.” The authors describe the subtletiesof the approach in a clear andconcise manner. As they note, the extendedtransbasal approach allows forexcellent access, which can be modifiedto meet the specific surgical need.

Drs. Chandler and Silva do agood job describing the bifrontalbiorbital sphenoethmoidalapproach to the skull base.This approach allows full access tothe anterior skull base, the paranasalsinuses between the medial thirds ofthe maxillary sinuses, and the entireclivus medial to the carotid arteriesand the hypoglossal nerves and belowthe pituitary gland. It should berecognized that the full extent of theapproach is not always necessary, anda good degree of tailoring is possible.Specifically, I have not found it necessaryto perform orbital osteotomiesfor access to the paranasal sinuses orfor cribriform plate resection. A smallmidline frontal craniotomy with aninferior extension to the level of thefrontonasal suture is usually sufficient.

In this manuscript, Drs. Chandlerand Silva describe the extendedtransbasal approach as a modificationof the commonly used frontoorbitalcraniotomy, which maximizesanterior skull base exposure whileminimizing brain retraction. This conceptis now in its ninth decade, havingbeen described by Frazier inrudimentary form in 1913.[1] The approachwas subsequently reported ina more formalized fashion in the Europeanliterature by Derome and thenexpanded upon by various surgeonsin the United States.[2-4]

Anne McTiernan has provideda comprehensive and balancedreview of a complex topic,namely, “Obesity and Cancer: TheRisks, Science, and Potential ManagementStrategies.” The impressiveweight of assembled evidence from thecited observational studies has been sufficientto influence several cancer organizations,including the AmericanCancer Society and the American Institutefor Cancer Prevention, to issuerecommendations regarding nutritionand physical activity in relationship tocancer.[1,2] However, clinical practiceis unlikely to undergo substantialchange in the absence of prospectivetrials demonstrating benefit on clinicaloutcomes.[3] For at least the breast cancerand obesity question, informationfrom phase III randomized, prospectiveclinical trials evaluating lifestyleintervention influence on clinical outcomeare anticipated in the near future.

Overweight and obesity increase the risk of developing several cancers.Once cancer develops, individuals may be at increased risk of recurrenceand poorer survival if they are overweight or obese. A statisticallysignificant association between overweight or obesity and breast cancerrecurrence or survival has been observed in the majority of populationbasedcase series; however, adiposity has been shown to have less of aneffect on prognosis in the clinical trial setting. Weight gain after breastcancer diagnosis may also be associated with decreased prognosis. Newevidence suggests that overweight/obesity vs normal weight may increasethe risk of poor prognosis among resected colon cancer patients and therisk of chemical recurrence in prostate cancer patients. Furthermore, obesecancer patients are at increased risk for developing problems followingsurgery, including wound complication, lymphedema, second cancers,and the chronic diseases affecting obese individuals without cancer suchas cardiovascular disease and diabetes. Mechanisms proposed to explainthe association between obesity and reduced prognosis include adiposetissue-induced increased concentrations of estrogens and testosterone,insulin, bioavailable insulin-like growth factors, leptin, and cytokines.Additional proposed mechanisms include reduced immune functioning,chemotherapy dosing, and differences in diet and physical activityin obese and nonobese patients. There have been no randomized clinicaltrials testing the effect of weight loss on recurrence or survival inoverweight or obese cancer patients, however. In the absence of clinicaltrial data, normal weight, overweight, and obese patients should beadvised to avoid weight gain through the cancer treatment process. Inaddition, weight loss is probably safe, and perhaps helpful, for overweightand obese cancer survivors who are otherwise healthy.

Dr. McTiernan provides a comprehensive,thoughtful overviewof several studies thathave focused on obesity and cancer.She discusses the preponderance ofdata that have shown both a directrelationship between obesity and thedevelopment of cancer as well as adirect relationship between obesityand cancer recurrence. Although bothrelationships are clinically relevant,the latter is particularly important tocancer health-care providers. Today,more than ever before, cancer patientsare diagnosed early and treated effectively,thereby yielding a sizable cohortof cancer survivors and potentialcancer survivors.[1] Understandingthe relationship between obesity oroverweight status and cancer recurrenceis now more timely than it hasever been.

Thromboembolism affects many patients with solid tumors and clonalhematologic malignancies. Pathogenetic mechanisms include inflammatory-and tissue factor-mediated coagulation, natural anticoagulantdeficiencies, fibrinolytic alterations, hyperviscosity, and activationof platelets, endothelial cells, and leukocytes. High rates of venousthromboembolism (VTE) occur with advanced pancreatic, breast, ovarian,germ cell, lung, prostate, and central nervous system cancers.Hodgkin disease, non-Hodgkin's lymphoma, myeloma, paroxysmalnocturnal hemoglobinuria, and certain leukemias also predispose tovenous thromboembolism. Arterial and venous events occur with polycythemiavera and essential thrombocythemia. Central venous cathetersand prothrombotic antitumor regimens augment the risk in somepatients. Part 1 of this two-part article addresses pathophysiology, clinicalpresentations, and risk of malignancy-associated thrombosis. Part 2,which will appear in next month's issue, covers prophylaxis and treatmentof these thromboembolic complications.

Argiris et al present a comprehensivereview of inductionchemotherapy for head andneck cancer, and should be lauded fortheir meticulous work. This papercarefully delineates and categorizesmost of the relevant induction chemotherapystudies in head and neckcancer performed over the past 3 decades.The authors have sought to answerquestions regarding the optimalnumber of chemotherapy cycles (acritical factor when one uses responseto induction chemotherapy to determineeligibility for organ preservationor in an attempt to enhance curerates), the optimal chemotherapyregimen, and the possibility of a sitespecificbenefit to induction chemotherapy.The paper assesses benefitbased on treatment intent-that is, organpreservation vs survival benefit.Importantly, by excavating the layersof the past, the authors provide aframework with which to construct anew paradigm of treatment for headand neck cancer that may again incorporateinduction chemotherapy.

Argiris and colleagues presenta comprehensive review of25 years of phase II/III trialsusing multimodality therapy for locallyadvanced head and neck squamouscell cancer (HNSCC). Theyfocus on two approaches: inductionchemotherapy followed by definitivelocal therapy (surgery and/or radiotherapy)and concurrent chemoradiotherapy.In sorting through thesetrials, the authors review the controversiesin the management of locallyadvanced HNSCC, while also presentinga rationale for a unified approach-combining induction andconcomitant chemoradiotherapy in amultimodality treatment paradigm.Evidence from several recent studiessuggests that this strategy will benefita subset of patients with locally advanceddisease. The stage is set forthe reevaluation of the benefit of inductionchemotherapy prior to definitivechemoradiation. To that end, threedifferent prospective phase III trialsare under way in the United States.

Argiris and colleagues report asystematic review evaluatingthe activity and potential roleof induction chemotherapy in patientswith previously untreated, locoregionallyadvanced squamous cell head andneck cancer.[1] They consider bothphase II and III published trials. Thedata reviewed in their paper, and theirthoughtful synthesis and interpretationof these data, highlight certain themes:

This excellent summary of theassociation of overweight andobesity with increased incidenceand poorer prognosis in a varietyof cancers is well worth the reader'sattention. Dr. McTiernan presents literaturesuggesting that overweight isassociated with increased incidenceand mortality in a variety of types ofcancer. In the case of breast cancer,for which there are more data than anyother cancer site, the increased risk ofmortality appears to be in part relatedto increased incidence in postmenopausalwomen, and to a poorer prognosisassociated with both overweightand weight gain following diagnosis.

A variety of novel surgical approaches have been developed in recentyears to manage disease of the cranial base. Few offer the widthand depth of exposure achievable with the extended transbasal approach.This approach combines a bifrontal craniotomy with anorbitonasal or orbitonasoethmoidal osteotomy, and potentially asphenoethmoidotomy to provide broad access to malignancies of theanterior, middle, and posterior skull base. The approach enables the enbloc resection of tumors within the frontal lobes, orbits, paranasal sinuses,and sphenoclival corridors without brain retraction and mayobviate the need for transfacial access. This can be combined with additionalapproaches, based on the tumor's epicenter. Reconstruction isaccomplished with the use of pericranium, and in some instances, atemporalis muscle pedicle or a gracilis microvascular free flap. Complicationsinclude cerebral spinal fluid leakage, pneumocephalus, infection,and cranial neuropathies. However, the morbidity and mortalityassociated with this approach is low. The extended transbasal approachis a relatively novel exposure that enables the skilled cranialbase surgeon to safely excise many malignant lesions previously felt tobe unresectable.