ONCOLOGY Vol 17 No 6

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.

The "Update on Breast CancerPrevention" by Rastogi andVogel provides a comprehensiveand balanced review of the currentstatus of breast cancer chemoprevention.Several areas that the authorsaddress warrant further attention.

The most common malignant tumorsfrequently metastasize tothe skeleton. Although bonemetastases occur frequently with nearlyall tumors, some cancers (eg, breastand prostate cancer) have a specialpredilection for the skeleton. Complicationsassociated with skeletal metastasessubstantially erode thepatient’s quality of life. These skeletal-related events (SREs) include spinalcord compression, fracture,surgery, radiation therapy, and hypercalcemia.On average, patients withbone metastases experience three tofour SREs per year (one every 3 to 4months). In addition, they frequentlyhave pain and require narcotics, whicherode their quality of life.

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.

Four randomized prospective trials have evaluated tamoxifen forchemoprevention of breast cancer. The National Surgical AdjuvantBreast and Bowel Project P-1 trial reported that tamoxifen reduced therisk of invasive breast cancer by 49%. Two smaller European trials, theRoyal Marsden Hospital Chemoprevention Trial and the Italian TamoxifenPrevention Study, demonstrated no decrease in the incidence ofbreast cancer among women using tamoxifen. The International BreastCancer Intervention Study confirmed that tamoxifen can reduce therisk of breast cancer in healthy women. The Multiple Outcomes ofRaloxifene Evaluation trial, which evaluated the use of raloxifene(Evista) to prevent osteoporosis, found that the risk of invasive breastcancer decreased by 76%. A uniform theme in these trials is thattamoxifen reduces the risk of breast cancer among women at high riskfor the disease. Tamoxifen is currently approved for breast cancer riskreduction. However, because of the side effects associated with its use(ie, endometrial cancer and thromboembolism), other agents are beinginvestigated. The Study of Tamoxifen and Raloxifene is designed tocompare the efficacy of tamoxifen and raloxifene in reducing breastcancer risk. Aromatase inhibitors will also be studied in the setting ofchemoprevention for breast cancer.

Breast cancer is the most commonmalignancy diagnosed inAmerican women today. Giventhe frequency of the diagnosis, approachesthat reduce breast cancerincidence also have the potential toprovide a major impact on morbidityof the disease and its treatment, costto the individual and to society, andoverall cancer mortality. In their paper,Rastogi and Vogel present a conciseand comprehensive review of thefour prospective randomized clinicaltrials of tamoxifen for chemopreventionof breast cancer, as well as ongoingand future studies examininghormonal alternatives to tamoxifen.

Bone is the most frequent andimportant site of metastaticcancer and is responsible foran enormous clinical burden and demandon health-care resources. Blumand colleagues comprehensively reviewthe management of bone metastases,argue for a more integratedcare pathway, and underscore the importanceof bone-specific treatmentsin reducing skeletal complications tomaintain quality of life and physicalfunctioning.

This review by Dr. Gore emphasizesthe significance of theproblem of brain metastases inpatients with locally advanced non–small-cell lung cancer (NSCLC). Thearticle should prompt medical and radiationoncologists to consider enrollingpatients in the ambitious study ofprophylactic cranial irradiation (PCI)led by the Radiation Therapy OncologyGroup (RTOG L-0214). Statisticsfrom the ongoing RTOG study arecomplicated, but essentially, the researchersare looking for a 20% increasein median survival for patientsreceiving PCI. This would make theimpact of PCI in NSCLC comparableto that observed in limited small-celllung cancer (SCLC).

Drs. Baidas, Cheson, Kauh, and Ozdemirli present a thorough and balanced review of mantle cell lymphoma (MCL) and the various current treatment options. MCL has been recognized as a distinct pathologic entity for over a decade. It represents 6% to 9% of all non- Hodgkin’s lymphoma cases, and the diagnosis is based on a combination of morphologic, immunophenotypic, and cytogenetic criteria as discussed in the article. The hallmark of MCL is t(11;14)(q13;q32), a translocation that juxtaposes the Bcl-1 gene on chromosome 11 and immunoglobulin (Ig)H promoter on chromosome 14, leading to overexpression of cyclin D1. Although it had been considered an indolent lymphoma for many years, MCL has a poor prognosis with short remissions and a median survival of 3 to 4 years.[1,2]

Over the past decade, studies have shown improved survival inpatients with locally advanced non–small-cell lung cancer. This can beattributed to better systemic therapy, growing experience with combined-modality therapy, technologic advances allowing for increasedradiation doses, better supportive care, and better patient selection.With longer survival, we are seeing an increase in the incidence ofcentral nervous system (CNS) metastases. Prophylactic cranial irradiation(PCI) decreases the incidence of CNS metastases in these patientsand may have a favorable impact on quality of life and overall survival.This paper reviews the incidence of CNS metastases in non–small-celllung cancer patients, past experience with PCI, and a current studyevaluating the impact of PCI on survival, neuropsychological function,and quality of life.

With recent advances in the management of cancer, the clinicalcourse of patients with metastatic bone disease is more likely to beprolonged and accompanied by morbidity, including severe pain, hypercalcemia,pathologic fracture, and spinal cord and/or nerve root compression.The early identification of patients at higher risk for developingbone metastases enables practitioners to be proactive in their diagnosisand treatment. A multidisciplinary approach that integrates the diagnosisand treatment of the cancer, symptom management, and rehabilitationensures optimal care. Bisphosphonates can reduce the number ofskeletal-related complications, delay the onset of progressive disease inbone, and relieve metastatic bone pain caused by a variety of solidtumors with a resulting enhanced quality of life. The complexity of theclinical problem and the need to involve an array of health-careproviders present a logistical and clinical challenge. A strong argumentis made for a thematically integrated bone metastases program as partof the primary care of patients with cancer.