Showing papers in "Journal of The National Comprehensive Cancer Network in 2009"

NCCN clinical practice guidelines in oncology: kidney cancer.

Abstract: The number of new cases of renal cell carcinoma has been steadily increasing since the 1960s, reaching 62,000 and 89,000 annually in the United States and Europe, respectively, in 2016. The current standard of care for early-stage disease is nephron-sparing surgery, which has a demonstrated long-term disease-free survival and an acceptable safety profile. Technical developments (thin, powerful probes and real-time image guidance systems) have allowed image-guided percutaneous ablation to become a viable option for stage I renal cell carcinoma. Because of the widespread use of cross-sectional imaging, most renal tumors (75%) are indeed detected incidentally at stage I (75%). As a result, ablation is a potentially curable intervention and one that could mitigate surgical risks. All 3 ablative modalities (radiofrequency ablation, microwave ablation, and cryoablation) have been extensively applied. The utilization of ablation was initially hampered by the lack of prospective, long-term oncologic data. As a result, ablation was reserved for specific subgroups of patients, for example, patients with solitary kidney, chronic kidney disease, or bilateral disease; poor surgical candidates; or patients with syndromes that predispose them to renal cell cancer. Recently, however, studies on percutaneous ablation for early-stage renal cancer have yielded prospective, long-term oncologic data, affirming the earlier, lower-level-evidence studies. The reported efficacy of ablation for stage I renal cancer (especially cryoablation) appears to rival that of the accepted standard of care (nephron-sparing surgery), whereas its safety profile is a decided advantage. In conclusion, image-guided percutaneous ablation should be considered a viable, curative option for stage IA renal cell carcinoma.

Breast cancer screening and diagnosis: Clinical practice guidelines in oncology™

Abstract: The intent of these guidelines is to give health care providers a practical, consistent framework for screening and evaluating a spectrum of breast lesions. Clinical judgment should always be an important component of optimal management. If the physical breast examination, radiologic imaging, and pathologic findings are not concordant, the clinician should carefully reconsider the assessment of the patient's problem. Incorporating the patient into the health care team's decision-making empowers the patient to determine the level of breast cancer risk that is personally acceptable in the screening or follow-up recommendations.

Impact of chemotherapy dose intensity on cancer patient outcomes

Abstract: Chemotherapy dose intensity represents unit dose of chemotherapy administered per unit time. Dose intensity can be increased or decreased through altering dose administered, time interval of administration, or both. Evidence supporting the importance of delivered chemotherapy dose intensity on clinical outcomes in patients with potentially curable malignancies comes from in vitro studies of cancer cell lines and abundant in vivo preclinical studies, in addition to retrospective and prospective clinical trials in both advanced and early-stage disease settings. Myelosuppression continues to represent the major dose-limiting toxicity of cancer chemotherapy, resulting in considerable morbidity and mortality along with frequent reductions in chemotherapy dose intensity, which may compromise disease control and survival. Several retrospective and prospective randomized trials have shown that reductions in the chemotherapy dose intensity established in efficacy studies may compromise long-term disease control and survival. Despite compelling data, surveys in the United States and elsewhere have reported that dose reductions and delays frequently occur in clinical practice, even in the potentially curative setting. Alternatively, an increase in dose intensity above standard may be achieved through either increasing the dose of individual agents (dose escalation) or compressing or shortening the treatment interval (dose-dense). In early studies, dose-dense schedules showed an increase in survival, whereas the benefit of dose escalation studies has been less consistent and may be accompanied by other dose-limiting toxicities. This article focuses on the rationale for delivering full chemotherapy dose intensity, the apparent reasons for failing to deliver treatment, and available strategies for sustaining full chemotherapy dose intensity when indicated. The delivery of full chemotherapy dose intensity in patients with potentially curable malignancies should be considered a quality of care indicator in clinical oncology.

The Challenges of Colorectal Cancer Survivorship

Abstract: With advances in treatment, colorectal cancer (CRC) is being transformed from a deadly disease into an illness that is increasingly curable. With this transformation has come increased interest in the unique problems, risks, needs, and concerns of survivors who have completed treatment and are cancer-free. Research has shown that physical and mental quality of life for CRC survivors was inferior compared with age-matched individuals without cancer. Although issues and symptoms were most prominent during the first 3 years, long-term effects of treatment can persist and include fatigue, sleep difficulty, fear of recurrence, anxiety, depression, negative body image, sensory neuropathy, gastrointestinal problems, urinary incontinence, and sexual dysfunction. The unique challenges and issues of CRC survivors can and should be addressed by health care providers and the research community to ensure effective interventions and models of care to manage these problems. This article discusses what is known about the long-term effects of CRC treatment on quality of life, the care of survivors, and existing models of survivorship care.

NCCN clinical practice guidelines in oncology: palliative care.

Abstract: These guidelines were developed and updated by an interdisciplinary group of experts based on clinical experience and available scientific evidence. The goal of these guidelines is to help patients with cancer experience the best quality of life possible throughout the illness trajectory by providing guidance for the primary oncology team for symptom screening, assessment, palliative care interventions, reassessment, and afterdeath care. Palliative care should be initiated by the primary oncology team and augmented by collaboration with an interdisciplinary team of palliative care experts.

NCCN Task Force Report: Management of Neuropathy in Cancer

Abstract: Neuropathy is a common, often debilitating complication of cancer and its treatment. Effective management of this disorder depends on early diagnosis and an understanding of its underlying causes in the individual patient. In January 2009, NCCN gathered a multidisciplinary group to review the literature and discuss intervention strategies currently available to patients as well as areas that require research efforts. The task force, which comprised experts in anesthesiology, medical oncology, neurology, neuro-oncology, neurophysiology, nursing, pain management, and rehabilitation, was charged with the goal of outlining recommendations for the possible prevention, diagnosis, and management of neuropathy. This report documents the proceedings of this meeting with a general background on neuropathy and neuropathy in oncology, followed by discussions on challenges and research issues, evaluation criteria, and management of different symptoms associated with this disorder.

Myeloid Growth Factors

Abstract: Febrile neutropenia, a common side effect of myelosuppressive chemotherapy in patients with cancer, can result in prolonged hospitalization and broad-spectrum antibiotic use, often prompting treatment delays or dose reductions of drug regimens. Prophylactic use of myeloid growth factors (mainly the colony-stimulating factors filgrastim and pegfilgrastim) in patients of heightened risk can reduce the severity and duration of febrile neutropenia. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myeloid Growth Factors provide recommendations on the use of these agents mainly in the oncology setting based on clinical evidence and expert consensus. This version includes revisions surrounding the issue of timing of pegfilgrastim administration. It also includes new sections on tbo-filgrastim, a recently approved agent that is biologically similar to filgrastim, and the role of myeloid growth factors in the hematopoietic cell transplant setting.

NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia.

Abstract: The treatment options for chronic myelogenous leukemia (CML) continue to evolve rapidly. Imatinib mesylate (Gleevec, Glivec, formerly STI571) has continued to show remarkable clinical benefits and the updated results with this agent are reviewed. As relapses using single agent imatinib have occurred, particularly in advanced phase patients, the issue of whether combinations of other antileukemic agents with imatinib may yield improved results is addressed. In addition, data on new agents that have potential in the treatment of CML are reviewed. These agents are presented in the context of their molecular mechanism of action. The most recent data for stem cell transplantation, along with advances in nonmyeloablative transplants, are also reviewed. In Section I, Drs. Stephen O'Brien and Brian Druker update the current status of clinical trials with imatinib and review ongoing investigations into mechanisms of resistance and combinations of imatinib with other agents. They also present their views on integration of imatinib with other therapies. In Section II, Dr. Jorge Cortes describes the most recent data on novel therapies for CML, including farnesyl transferase inhibitors, arsenic trioxide, decitabine, and troxatyl, among others. These agents are discussed in the context of their molecular mechanism of action and rationale for use. In Section III, Dr. Jerald Radich updates the results of stem cell transplants for CML, including emerging data on nonmyeloablative transplants. He also presents data on using microarrays to stratify patients into molecularly defined risk groups.

NCCN Task Force Report: Estrogen receptor and progesterone receptor testing in breast cancer by immunohistochemistry

Abstract: The NCCN Task Force on Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry was convened to critically evaluate the extent to which the presence of the estrogen receptor (ER) and progesterone receptor (PgR) biomarkers in breast cancer serve as prognostic and predictive factors in the adjuvant and metastatic settings, and the ability of immunohistochemical (IHC) detection of ER and PgR to provide an accurate assessment of the expression of these biomarkers in breast cancer tumor tissue. The task force is a multidisciplinary panel of 13 experts in breast cancer who are affiliated with NCCN member institutions and represent the disciplines of pathology, medical oncology, radiation oncology, surgical oncology, and biostatistics. The main overall conclusions of the task force are ER is a strong predictor of response to endocrine therapy; ER status of all samples of invasive breast cancer or ductal carcinoma in situ (DCIS) should be evaluated by IHC; IHC measurements of PgR, although not as important clinically as ER, can provide useful information and should also be performed on all samples of invasive breast cancer or DCIS; IHC is the main testing strategy for evaluating ER and PgR in breast cancer and priority should be given to improve the quality of IHC testing methodologies; all laboratories performing IHC assays of ER and PgR should undertake formal validation studies to show both technical and clinical validation of the assay in use; and all laboratories performing IHC assays of hormone receptors in breast cancer should follow additional quality control and assurance measures as outlined in the upcoming guidelines from the American Society of Clinical Oncology and College of American Pathologists.

Role of sentinel lymph node biopsy in patients with thin melanoma.

Abstract: Sentinel lymph node (SLN) biopsy has emerged over the past 2 decades as a rational approach for staging regional lymph nodes in patients with clinically node-negative melanoma (stage I and II disease). Large multi-institutional studies have confirmed that when performed by experienced surgeons, it is an accurate, reliable technique for identifying occult regional nodal disease, and that SLN status is the most important prognostic factor in patients with, stage I and II melanoma. However, the incidence of occult regional nodal metastasis in patients with thin melanoma (≤ 1.0 mm; approximately 70% of patients with newly diagnosed melanoma) is low, and whether to perform SLN biopsy in these patients remains controversial. Several predictors of SLN metastasis in patients with thin melanoma have been suggested, but none widely accepted. This article reviews current literature on these predictors in patients with thin melanoma. Although the ability to draw conclusions was limited by the size and design of the available studies, the authors tentatively conclude that SLN biopsy can be considered for patients with melanomas 0.75 mm or larger, those with T1b melanomas (i.e., ≤ 1.0 mm; Clark level IV/V and/or ulcerated), and those with thin melanomas with an increased tumor mitotic rate (especially ≥ 1 mitosis/mm 2 ). Including younger age (e.g., ≤ 40 years) in the decision also seems reasonable, particularly if the primary tumor is associated with a high tumor mitotic rate. Tumor regression does not seem to be associated with an increased risk for SLN metastasis. Firm conclusions on the predictive value of vertical growth phase, absence of tumor-infiltrating lymphocytes, or male gender were not possible, particularly if used as a sole criterion for offering this procedure. SLN biopsy should be discussed with all patients with newly diagnosed thin melanoma.

NCCN Task Force Report: Management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer.

Abstract: This NCCN Task Force Report describes the management of dermatologic and ocular toxicities that occur in patients treated with epidermal growth factor receptor (EGFR) inhibitors. Task force members are from NCCN member institutions and include oncologists, dermatologists, an ophthalmologist, and a mid-level oncology provider. This report describes commonly used therapies that the task force agreed are appropriate standards of care for dermatologic and ophthalmologic toxicities associated with EGFR inhibitors, which generally are supported only by anecdotal evidence. Few recommendations are evidence based; however, some commonly used therapies have data supporting their use. Conclusions from completed clinical trials are generally limited by the small numbers of patients enrolled. The information in this report is based on available published data on treating toxicities associated with EGFR inhibitors, data from treatment of clinically similar toxicities from different etiologies, and expert opinion among the NCCN Task Force members.

NCCN task force: clinical utility of PET in a variety of tumor types.

Abstract: Use of PET is widespread and increasing in the United States, mainly for oncologic applications. In November 2006, the National Comprehensive Cancer Network (NCCN) gathered a panel of experts to review the literature and develop clinical recommendations for using PET scans in lymphoma and non-small cell lung, breast, and colorectal cancers. However, because its use is not restricted to these diseases, and evidence is accumulating for its application in other types of cancers, NCCN convened a second meeting in December 2008 to expand on the initial report. A multidisciplinary panel met to discuss the current data on PET application for various tumor types, including genitourinary, gynecologic, pancreatic, hepatobiliary, thyroid, brain, small cell lung, gastric, and esophageal cancers, and sarcoma and myeloma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, the role of PET in oncology, principles of PET use, emerging applications, and possible future developments.

The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors.

Abstract: Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis.

Indications for breast MRI in the patient with newly diagnosed breast cancer.

Abstract: Use of breast MRI in the preoperative evaluation of patients recently diagnosed with breast cancer has increased significantly over the past 10 years because of its well-documented high sensitivity for detecting otherwise occult breast cancer in the affected and contralateral breasts. However, published research reports on the impact of this improved cancer detection are limited. Equally important are growing concerns that the quality of breast MRI may vary significantly across practice sites, and therefore the published value of MRI may not be achieved for many patients. This article describes the peer-reviewed, published clinical research trials evaluating breast MRI in patients with newly diagnosed breast cancer on which the National Comprehensive Cancer Network (NCCN) practice guidelines are based. The current NCCN guidelines recommend that breast MRI be considered for patients with a newly diagnosed breast cancer to evaluate the extent of ipsilateral disease and to screen the contralateral breast, particularly for women at increased risk for mammographically occult disease. In addition, the guidelines indicate that breast MRI may be used for patients with axillary nodal adenocarcinoma to identify the primary malignancy. The guidelines stress the importance of having proper equipment, imaging technique, and provider training necessary to achieve high-quality breast MRI, and emphasize that MRI practice sites should have the ability to perform MRI-guided biopsy or needle localization. In addition to describing the data regarding use of breast MRI in women with newly diagnosed cancer, this article provides recommendations for the performance of high-quality breast MRI and suggestions for future research.

Merkel cell carcinoma

Abstract: (Staging for Merkel Cell of the eyelid [C44.1] is not included in this chapter – see Chap. 48, “Carcinoma of the Eyelid” in the AJCC Cancer Staging Manual)

Carcinosarcomas (Malignant Mixed Müllerian Tumor) of the Uterus: Advances in Elucidation of Biologic and Clinical Characteristics

Abstract: Carcinosarcoma of the uterus (malignant mixed Mullerian tumor [MMMT]) is an uncommon, typically extremely aggressive neoplasm histologically composed of malignant epithelial and mesenchymal (stromal) elements. Although the literature contains some debate, most authors now agree that most MMMTs derive from sarcomatous differentiation in a high-grade carcinoma. This article reviews the clinical and histopathologic features of this interesting neoplasm, with particular emphasis on recent data supporting MMMTs as primarily epithelial malignant neoplasms with areas of mesenchymal/spindle cell differentiation.

Concordance with NCCN Colorectal Cancer Guidelines and ASCO/NCCN Quality Measures: An NCCN Institutional Analysis

Abstract: Background The National Comprehensive Cancer Network (NCCN) Outcomes Database was created to assess concordance to evidence- and consensus-based guidelines and to measure adherence to quality measures on an ongoing basis. The Colorectal Cancer Database began in 2005 as a collaboration among 8 NCCN centers. Methods Newly diagnosed colon and rectal cancer patients presenting to 1 of 8 NCCN centers between September 1, 2005, and May 21, 2008, were eligible for analysis of concordance with NCCN treatment guidelines for colorectal cancer and with a set of quality metrics jointly developed by ASCO and NCCN in 2007. Adherence rates were determined for each metric. Center-specific rates were benchmarked against mean concordance rates for all participating centers. Results A total of 3443 patients were evaluable. Mean concordance rates with NCCN colorectal cancer guidelines and ASCO/NCCN quality measures were generally high ( >or= 90%). However, relatively low mean concordance rates were noted for adjuvant chemotherapy treatment recommendations within 9 months of diagnosis of stage II to III rectal cancer (81%), and neoadjuvant chemoradiation in clinical T4 rectal primaries (83%). These low rates of concordance seemed to be consistent across centers. Conclusions Adherence to guidelines and quality measures is generally high at institutions participating in the NCCN colorectal cancer database. Lack of documentation, patient refusal, delayed treatment initiation, and lack of consensus about whether treatment was essential were the primary reasons for nonconcordance. Measurement of concordance and the reasons for nonconcordance enable participating centers to understand and improve their care delivery systems.

Management of adrenocortical carcinoma.

Abstract: Adrenocortical carcinomas (ACCs) are rare tumors that arise from the cortex of the adrenal gland with an incidence 1 to 2 per million. The rarity of this tumor translates into a paucity of experience in managing patients in most medical centers. Because clinical series are small and prospective evaluation of treatment strategies is limited, the current state of knowledge is strongly influenced by expert consensus opinion from a few medical centers specializing in ACCs. This article describes the basic diagnostic and prognostic issues in adrenal cancer management, and presents detailed rationales for therapeutic management.

Pharmacogenetics of Tamoxifen: Who Should Undergo CYP2D6 Genetic Testing?

Abstract: Many women with hormone receptor-positive breast cancer will receive tamoxifen at some point in their treatment course. Tamoxifen is biotransformed to the potent antiestrogen endoxifen almost exclusively through the cytochrome P450 (CYP) 2D6 isoform. Although prospective data are lacking, the balance of evidence available currently suggests that a single nucleotide polymorphism in the CYP2D6 gene, particularly the presence of 2 null alleles, predicts for reduced tamoxifen metabolism and possibly poorer outcome than expected in patients with a wild-type genotype. Studies evaluating the impact of genetic polymorphisms that result in CYP2D6 with reduced or no activity on long-term outcome have been mostly retrospective and conducted on archival tissues or those obtained previously in prospective studies of tamoxifen. Until data are available from retrospective examinations of the large prospective trials already conducted, or adequately powered prospective analyses, transforming this information into guidelines for individual patients remains challenging. The authors do not currently recommend routine testing for CYP2D6 genotype for making clinical decisions regarding tamoxifen. Use of concomitant strong or intermediate inhibitors of CYP2D6 should be avoided when alternate medications are available. Ongoing research is directed toward identifying other polymorphisms that may influence the efficacy and safety of tamoxifen, other hormonal agents, and chemotherapies used to treat breast cancer. The hope is that in the future, not only tumor-associated factors but also germ-line host genetics can be used to determine whether a woman should receive treatment, and with which specific agents, to prevent breast cancer recurrence or death or avoid drug-related toxicities.

Hematopoietic stem cell transplantation in multiple myeloma.

Abstract: The introduction of novel agents (thalidomide, bortezomib, lenalidomide) is changing the management of patients with multiple myeloma who are candidates for stem cell transplantation Bortezomib-dexamethasone given as induction treatment before autologous stem cell transplantation is significantly superior to the classical vincristine-doxorubicin-dexamethasone regimen in terms of complete response and very good partial response, both before and after transplantation Triple combinations with thalidomide and bortezomib plus either cyclophosphamide or doxorubicin also yield excellent response rates, with the combination of bortezomib with thalidomide and dexamethasone seeming to be the most promising Postautologous transplantation maintenance with thalidomide improves the response rate, progression-free survival, and, in some subgroups, overall survival However, the optimal dose and duration of administration of thalidomide is not known Both lenalidomide and bortezomib are being evaluated in this setting The addition of novel agents before and after autotransplant yields a very high complete response rate and prolonged progression-free and overall survival However, outstanding results have also been achieved with novel agents without transplantation Therefore, randomized trials comparing novel agents with and without early transplantation are awaited Tandem autologous plus reduced-intensity conditioning allogeneic transplantation have replaced myeloablative conditioning allogeneic transplantation Despite improved results and decreased toxic death rate, this approach still carries the risk for morbidity and mortality related to graft-versus-host disease and should not be proposed in front-line therapy, especially in patients with no adverse prognostic features

Carcinoma in situ of the urinary bladder: review of clinicopathologic characteristics with an emphasis on aspects related to molecular diagnostic techniques and prognosis.

Abstract: Carcinoma in situ (CIS) of the urinary bladder is defined as a flat lesion comprising of cytologically malignant cells which may involve either full or partial thickness of the urothelium. De novo CIS constitutes less than 3% of all urothelial neoplasms; however, CIS detected concurrently or secondarily during follow-up of urothelial carcinoma constitutes 45% and 90%, respectively, of bladder cancer. CIS is noted predominantly in male smokers in the sixth or seventh decade. Patients may present with dysuria, nocturia, and urinary frequency and urgency with microscopic hematuria. Cystoscopic findings may range from unremarkable to erythema or edema. Urine cytology is an important diagnostic tool. Cellular anaplasia, loss of polarity, discohesion, nuclear enlargement, hyperchromasia, pleomorphism, and atypical mitoses are the histopathologic hallmarks of CIS. Extensive denudation of the urothelium, monomorphic appearance of the neoplastic cells, inflammatory atypia, radiation induced nuclear smudging, multinucleation, and pagetoid spread of CIS may cause diagnostic difficulties. Together with clinical and morphologic correlation, immunostaining with CK 20, p53 (full thickness), and CD44 (absence of staining) may help accurately diagnose CIS. Fluorescent in situ hybridization analysis of voided urine for amplification of chromosomes 3, 7, and 17 and deletion of 9p has high sensitivity and specificity for diagnosing CIS in surveillance cases. Several other molecular markers, such as NMP 22 and BTA, are under evaluation or used variably in clinical pathology. Intravesical bacillus Calmette-Guerin (BCG) instillation is considered the preferred treatment, with radical cystectomy being offered to refractory cases. Chemotherapy, alpha-interferon, and photodynamic therapy are other modalities that can be considered in BCG-refractory cases. Multifocality, involvement of prostatic urethra, and response to BCG remain the most important prognostic factors, although newer molecular markers are being evaluated for this entity. Patient outcome varies based on whether it is de novo development or diagnosed secondary to prior or concomitant papillary bladder cancer. From a clinical perspective, the principal determinants of outcome are extent of disease, involvement of prostatic urethra, response to therapy, and time to recurrence.