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Even now, cancer is a disease ofaging; the average age of a newlydiagnosed cancer patient inthe United States is greater than 65years. Safe and effective medical carefor the elderly will become an increasinglyimportant issue as our populationages over the next severaldecades. By 2025, 20% of the USpopulation will be over the age of 65.It will be essential for physicians tobe well versed in assessing and treatingpatients in this age group in a mannerappropriate to their unique medicalneeds. As the population ages, and bettertreatment for other diseases contributesto longer life expectancy, theassessment and treatment of cancer inthe elderly will be an increasingly commonproblem for oncologists.

The review by Beth Peshkin andClaudine Isaacs in this issue ofONCOLOGY is an excellentoverview of the recognition, evaluation,and clinical management ofwomen with BRCA1 and BRCA2mutations. It is comprehensive andpractical, and emphasizes the approachthat a risk assessment and clinicalgenetics program might take tothe evaluation of an individual concernedabout the possibility thathereditary breast/ovarian cancer predispositionmight be present in herkindred. The authors clearly and conciselypresent the risks of breast, ovarian,and other cancers associated withBRCA1 and BRCA2 mutation carrierstatus, as well as some of the issues thathave arisen in the estimation of thoserisks. They provide a review of factorsthat may modify gene penetrance(cancer risks), and devote the finalsegment of their article to a clear andrational discussion of the surveillanceand preventive options available forthe management of the associatedbreast and ovarian cancer risks.

Assessing outcome after ablation is difficult because few studies with good long-term followup have evaluated local recurrence, disease-free survival, and overall survival after ablation. This and other limitations make it difficult to draw meaningful conclusions.

The number of older adults in the general population continues togrow. As their numbers rise, the elderly and the management of theirmedical problems must be of increasing concern for health-care professionals.Within this older population, cancer is a leading cause ofmorbidity and mortality. Although many studies have looked at the psychiatricimplications of cancer in the general population, few studiestackle the issues that may face the older adult with cancer. This articlefocuses on the detection and treatment of depression, anxiety, fatigue,pain, delirium, and dementia in the elderly cancer patient.

In this issue of ONCOLOGY,Winell and Roth review the veryimportant topic of assessment andtreatment of psychiatric symptoms inelderly cancer patients. Their reviewis comprehensive and practical. Thiscommentary further develops a numberof themes raised in their article.

In their article, Drs. Michener andBelinson make the case for treatingrecurrent ovarian cancer as achronic disease, with limiting morbidityand providing palliation of symptomstheir major goals. A review ofrecent literature would support their contention and management strategy.The cure rate for patients with recurrentovarian cancer is < 5%, and theaverage patient in the United Statesreceives more than five separate regimensof chemotherapy for recurrentdisease. Previous attempts at aggressivetreatment for recurrent disease haveshown, at best, very modest benefitwith significant expense and morbidity.What we are left with is a strategy oftrying to determine which patients maybenefit from aggressive salvage therapyand which are better managed witha chronic palliative attempt.

Despite major advances in cancerbiology and therapeutics,cancer and its treatment continueto cause devastating suffering,not only for the more than half a millionpatients who will die this yearfrom cancer, but also for many ofthose who will be successfully treated.[1] Symptom burden has a profoundimpact on the quality of life ofcancer patients across all stages of disease.Routine screening of ambulatorycancer patients identifies an average of7 to 10 distressing physical and psychologicalsymptoms per patient.[2]Even patients with a good performancestatus have a median of nine or moresymptoms.[3,4] Not surprisingly, theseverity and burden of symptoms nearthe end of life is even greater.[4]

Twenty years of research in controlling symptoms such as pain andnausea have shown persistent suboptimal performance by the US oncologysystem. The data suggest that some of the tools of palliative careprograms can improve physical symptoms of seriously ill patients at acost society can afford. To fix these problems will require recognitionof the symptoms or concerns, a system such as an algorithm or careplan for addressing each, measurement of the change, and accountabilityfor the change. Symptom assessment scales such as the EdmontonSymptom Assessment Scale or Rotterdam Symptom Check List work tomake symptoms manifest. Listing symptoms on a problem list is a necessarystep in addressing them. Physical symptoms such as pain can beimproved by use of computer prompts, algorithms, dedicated staff time,team management, or combinations of these strategies. Less concreteproblems such as medically appropriate goal-setting, integrating palliativecare into anticancer care sooner, and informing patients aboutthe benefits and risks of chemotherapy near the end of life require morecomplex solutions. We review what is known about symptom control inoncology, how and why some programs do better, and make suggestionsfor practice. Finally, we suggest a practical plan for using symptomassessment scales, listing the problems, and managing them accordingto algorithms or other predetermined plans.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

HOUSTON, TEXAS-Preliminarydata from a phase II study ofoxaliplatin (Eloxatin) and capecitabine(Xeloda) in patients with unresectablegallbladder and biliary tract cancersshow a response rate of 18% in

ORLANDO-XELOX (capecitabine[Xeloda] and oxaliplatin [Eloxatin])is effective and well tolerated asfirst-line treatment for elderly patients

ORLANDO - Combined immunochemotherapy results in superior remission rates and overall survival in recurrent follicular and mantle cell lymphoma, and providing rituximab (Rituxan) maintenance therapy prolongs duration of response, according to new findings presented by Martin Dreyling, MD, PhD, at the American Society of Clinical Oncology 41st Annual Meeting (abstract 6527 and abstract 6528). "Combined immunotherapy resulted in superior remission rates and survival rates," said Dr. Dreyling, of the University of Munich, Germany. "To the best of my knowledge, this is the first study that proves that on a solid base of data."

The two-part article, "ThromboembolicComplications ofMalignancy," by Drs. Linenbergerand Wittkowsky, provides a contemporaryand clear review of thepathogenesis, prevention, and treatmentof cancer-associated hypercoagulabilityand venous thrombosis. Questionsabout the cancer and coagulation connectioncontinue to abound and greatlyoutnumber evidence-based answers. Asthe relationship between cancer and coagulationgains attention from the medicaland surgical oncology communities(ie, not only from the coagulation community),the gap between questions andanswers will likely close.

The dosing of chemotherapy is,at best, an imperfect science.Long-standing convention hasus calculating body surface area totwo decimal places-a largely discreditedand unnecessary exercise-yet wehave so far failed to learn how to incorporatepotentially important variablesrelated to race, sex, and pharmacogenetics.This review, “ChemotherapyDosing in the Setting of Liver Dysfunction,”by Eklund et al highlightsanother limitation in our understandingof how to use chemotherapy: There islittle known about how to dose drugs inpatients with anything other than normalorgan function.

Advances in cancer treatmentover the past 50 years havecured or prolonged the life expectancyof many patients with cancer.These advances have accelerated overthe past 2 decades. Increasingly, physicianswho manage patients with cancerare turning their attention to the managementof the complications of malignancy,since these complications areoften avoidable, can shorten life spans,and can reduce quality of life.

Thromboembolism 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.

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.

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.

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.

Androgen-deprivation therapy, usually with combined androgenblockade, is standard initial treatment for advanced prostate cancer.With failure of initial treatment, as indicated by rising prostate-specificantigen (PSA) levels, second-line hormonal therapy is usually instituted.Over the past several years, it has become increasingly clear thatsystemic chemotherapy has an important role in hormone-refractorydisease. Phase II trials have demonstrated high PSA and measurabledisease response rates with taxane single-agent and combination treatments.One recent phase III trial showed that docetaxel (Taxotere)/estramustine (Emcyt) significantly improved overall survival, progression-free survival, and PSA response rate compared with mitoxantrone(Novantrone) plus prednisone. Another phase III trial demonstratedthat docetaxel given every 3 weeks plus prednisone significantly improvedoverall survival, PSA response rate, pain relief response rate,and quality of life compared with mitoxantrone and prednisone. Onthe basis of these findings, every-3-week docetaxel plus prednisone isnow considered standard first-line therapy for metastatic hormonerefractorydisease. There is considerable optimism that treatment canbe further improved. Studies of taxane combinations with bevacizumab(Avastin), thalidomide (Thalomid), bortezomib (Velcade), antisenseBcl-2 oligonucleotide, mTOR inhibitors, epidermal growth factor receptorinhibitors, and KDR inhibitors are under way. Randomized phaseIII trials in progress or planned are examining docetaxel in combinationwith imatinib mesylate (Gleevec) or calcitriol and docetaxel/prednisonein combination with bevacizumab and an antisense clusterincompound. Other promising systemic agents include epothilones andatrasentan, and promising vaccines include Provenge, GVAX, andProstvac.

Recent advances in treatment modalities for breast and prostate cancerhave resulted in an increasing number of patients that are cured orthat, despite residual disease, live long enough to start experiencingcomplications from cancer treatment. Osteoporosis is one such problemthat has been increasingly identified in cancer patients. Hypogonadismand glucocorticoid use are the two major causes of bone loss inthese patients. Osteoporosis is characterized by low bone mass and abnormalbone microarchitecture, which results in an increased risk offractures. Vertebral body and hip fractures commonly result in a drasticchange of quality of life as they can result in disabling chronic pain,loss of mobility, and loss of independence in performing routine dailyactivities, as well as in increased mortality. In patients with prostatecarcinoma, androgen-deprivation therapy by either treatment with agonadotropin-releasing hormone (GnRH) or bilateral orchiectomy resultsin increased bone turnover, significant bone loss, and increasedrisk of fractures. Patients with breast cancer are at increased risk forestrogen deficiency due to age-related menopause, ovarian failure fromsystemic chemotherapy, or from the use of drugs such as aromataseinhibitors and GnRH analogs. Several studies have indicated that theprevalence of fractures is higher in breast and prostate cancer patientscompared to the general population. Therefore, patients at risk for boneloss should have an assessment of their bone mineral density so thatprevention or therapeutic interventions are instituted at an early enoughstage to prevent fractures. This article will address the characteristicsof bone loss observed in breast and prostate cancer patients and potentialtreatments.

Approximately 70% to 80% of all patients who receive chemotherapyexperience nausea and vomiting, which can disrupt their lives in numerousways. Chemotherapy-induced nausea and vomiting (CINV) hastraditionally been classified according to three patterns: acute, delayed,and anticipatory. Additional classifications include refractory and breakthroughnausea and vomiting. The mechanisms by which chemotherapycauses nausea and vomiting are complex, but the most common isthought to be activation of the chemoreceptor trigger zone. An appreciationof the risk factors for developing CINV is important when matchingantiemetic treatment to risk. The emetogenicity of the chemotherapyregimen-generally categorized as high, moderate, low, or minimal-greatly affects a patient’s risk for developing CINV. In addition to establishedand emerging pharmacologic approaches to managing CINV,many complementary and integrated modalities may be options.Progress in CINV management must include a better understanding ofits etiology and a focus on prevention. This review will consider theetiology, assessment, and treatment of patients with CINV.

Small-cell lung carcinoma (SCLC) accounts for 20% to 25% of all new cases of lung cancer in the United States. It is estimated that approximately 42,000 new cases will occur in the United States in 1995 [1,2]. Of the various histologic types of lung cancer, small-cell is the most sensitive to chemotherapy and radiotherapy, yet overall outcome is poor, with only 5% to 10% of patients surviving 5 years from diagnosis.

With the advent of modern therapeutic and prophylactic regimens, bacterial infections have become more effectively controlled, while fungal and viral infections have emerged as more prominent complications in the management of immunocompromised patients.

Allogeneic marrow transplantation is used to reconstitute hematopoiesis in patients who have received myeloablative therapy for a hematologic malignancy or in patients with irreversible marrow failure, to reconstitute the immune system in patients with severe immunodeficiency, and to normalize metabolism in patients with select inherited metabolic deficiency disorders.

The indolent non-Hodgkin's lymphomas constitute a heterogeneous group of lymphoproliferative disorders usually associated with relatively prolonged survival. They are categorized based on pathologic and cytologic features, and, with few exceptions [1], they are almost exclusively of B-cell origin.

In the United States, cancer of the large bowel is the second most common cause of cancer deaths after cancer of the lung [1]. 1995 estimates place large bowel cancer as the third most common malignancy, behind lung and prostate carcinomas in men and behind lung and breast cancers in women.

Over the past four decades, the incidence and mortality rates for uterine cervical carcinoma have decreased in the United States by as much as 70% to 75% [1]. This improvement is among the largest seen for any cancer site and has been attributed to the use of cervical cytologic screening [2].

Despite an overall rise in the incidence of gastrointestinal malignancies in the United States, there has been a significant decrease in the incidence of adenocarcinoma of the stomach over the past few decades. Nevertheless, gastric carcinoma remains the eighth leading cause of cancer death in the United States [1].

Neuroendocrine tumors manifest in the gastrointestinal tract mainly as carcinoid and pancreatic islet-cell tumors. They comprise an interesting group of rare neoplasms that are derived from neuroendocrine cells interspersed within the gastrointestinal system amd throughout the body. Neuroendocrine tumors are well known for producing various hormonal syndromes and for their indolent clinical course in most patients, although some of these tumors do not produce hormones of clinical significance. Patients may have symptoms for many years before the diagnosis is suspected and confirmed.