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Journal of Clinical Oncology

Journal of Clinical Oncology RSS feed - Early Release
Journal of Clinical Oncology












Purpose

Multiple myeloma (MM) is disproportionately diagnosed in older adults; with the aging of the population, the number of older adults diagnosed with MM will increase by nearly 80% in the next two decades. Duration of survival has improved dramatically over the last 20 years, but the improvements in older adults have not been as great as those in younger adults with MM.

Methods

In this article, we address treatment approaches in older adults who are eligible for and those ineligible for high-dose therapy with autologous stem-cell transplantation as well as supportive care considerations and the potential role for geriatric assessment in facilitating decision making for older adults with MM.

Results

The evidence from recent studies demonstrates that combinations of novel and conventional antimyeloma agents result in improved response rates and, in some cases, improved progression-free and overall survival. However, some older adults are particularly vulnerable to toxicities of therapy and discontinuation of therapy and, consequently, they have poorer survival. In addition, older adults may prioritize other outcomes of therapy, such as quality of life, over more conventional end points such as disease response and duration of survival. Geriatric assessment can facilitate risk-stratification of older adults at greater risk for adverse events from therapy and aid in personalizing therapy for vulnerable or frail older adults.

Conclusion

Survival in older adults with MM is improving with novel therapeutics, but efficacy must be balanced with risk of toxicity of therapy and maintenance of quality of life. Novel instruments such as geriatric assessment tools may facilitate these aims.



Treatment of older adults with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is challenging because of disease morbidity and associated treatments. Both diseases represent a genetically heterogeneous group of disorders primarily affecting older adults, with treatment strategies ranging from supportive care to hematopoietic stem-cell transplantation. Although selected older adults can benefit from intensive therapies, as a group they experience increased treatment-related morbidity, are more likely to relapse, and have decreased survival. Age-related outcome disparities are attributed to both tumor and patient characteristics, requiring an individualized approach to treatment decision making beyond consideration of chronologic age alone. Selection of therapy for any individual requires consideration of both disease-specific risk factors and estimates of treatment tolerance and life expectancy derived from evaluation of functional status and comorbidity. Although treatment options for older adults are expanding, clinical trials accounting for the heterogeneity of tumor biology and aging are needed to define standard-of-care treatments for both disease groups. In addition, trials should include outcomes addressing quality of life, maintenance of independence, and use of health care services to assist in patient-centered decision making. This review will highlight available evidence in treatment of older adults with AML or MDS and unanswered clinical questions for older adults with these diseases.


Treatment for prostate cancer (PCa) has evolved significantly over the last decade. PCa is the most prevalent non-skin cancer and the second leading cause of cancer death in men, and it has an increased incidence and prevalence in older men. As a result, physicians and patients are faced with the challenge of identifying optimal treatment strategies for localized, biochemical recurrent, and advanced PCa in the older population. When older patients are appropriately selected, treatment for PCa results in survival benefits and toxicity profiles similar to those experienced in younger patients. However, underlying health status and age-related changes can have an impact on tolerance of hormonal therapy and chemotherapy in men with advanced disease. Therefore, the heterogeneity of the elderly population necessitates a multidimensional assessment to maximize the benefit of medical and/or surgical options. Providing clinicians with the requisite health status data on which to base treatment decisions would help ensure that older patients with PCa receive optimal therapy if it will benefit them and/or active surveillance or best supportive care if it will not. We provide a review of the existing evidence to date on the management of PCa in the older population.


The number of patients with cancer who are age 65 years or older (hereinafter "older") is increasing dramatically. One obvious aspect of cancer care for this group is that they are experiencing age-related changes in multiple organ systems, including the brain, which complicates decisions about systemic therapy and assessments of survivorship outcomes. There is a consistent body of evidence from studies that use neuropsychological testing and neuroimaging that supports the existence of impairment following systemic therapy in selected cognitive domains among some older patients with cancer. Impairment in one or more cognitive domains could have important effects in the daily lives of older patients. However, an imperfect understanding of the precise biologic mechanisms underlying cognitive impairment after systemic treatment precludes development of validated methods for predicting which older patients are at risk. From what is known, risks may include lifestyle factors such as smoking, genetic predisposition, and specific comorbidities such as diabetes and cardiovascular disease. Risk also interacts with physiologic and cognitive reserve, because even at the same chronological age and with the same number of illnesses, older patients vary from having high reserve (ie, biologically younger than their age) to being frail (biologically older than their age). Surveillance for the presence of cognitive impairment is also an important component of long-term survivorship care with older patients. Increasing the workforce of cancer care providers who have geriatrics training or who are working within multidisciplinary teams that have this type of expertise would be one avenue toward integrating assessment of the cognitive effects of cancer systemic therapy into routine clinical practice.


Minimizing toxicity while maximizing efficacy is a common goal in the treatment of any condition but its importance is underscored in the discipline of oncology because of the serious nature of many chemotherapeutic toxicities and the risk of cancer recurrence or disease progression. The challenge of achieving an optimal therapeutic index is especially augmented in the elderly population because of age-related metabolism changes and interacting concurrent medications. Additional factors, such as germline mutations in drug-metabolizing enzymes and other pharmacogenomic alterations, may have more pronounced effects in elderly patients, given their predisposition to altered pharmacokinetics and pharmacodynamics with resulting increased risk of toxicity. Examples of the possible interplay of these factors will be discussed using tamoxifen, paclitaxel, codeine, and fluorouracil as starting points. Limited participation of the elderly in many cancer trials, especially trials assessing drug exposure, makes much knowledge on the interaction of these patient and environmental factors speculative in nature but presents an opportunity for future research to achieve better optimization of chemotherapeutic agents in the elderly.


In older patients, radiation treatment plays a vital role in curative and palliative cancer therapy. Radiation treatment recommendations should be informed by a comprehensive, personalized risk-benefit assessment that evaluates treatment efficacy and toxicity. We review several clinical factors that distinctly affect efficacy and toxicity of radiation treatment in older patients. First, locoregional tumor behavior may be more indolent in older patients for some disease sites but more aggressive for other sites. Assessment of expected locoregional relapse risk informs the magnitude and timeframe of expected radiation treatment benefits. Second, assessment of the competing cancer versus noncancer mortality and morbidity risks contextualizes cancer treatment priorities holistically within patients’ entire spectrum and time course of health needs. Third, assessment of functional reserve helps predict patients’ acute treatment tolerance, differentiating those patients who are unlikely to benefit from treatment or who are at high risk for treatment complications. Potential radiation treatment options include immediate curative treatment, delayed curative treatment, and no treatment, with additional consideration given to altered radiation target, dose, or sequencing with chemotherapy and/or surgery. Finally, when cure is not feasible, palliative radiation therapy remains valuable for managing symptoms and achieving meaningful quality-of-life improvements. Our proposed decision-making framework integrates these factors to help radiation oncologists formulate strategic treatment recommendations within a multidisciplinary context. Future research is still needed to identify how advanced technologies can be judiciously applied in curative and palliative settings to enhance risk-benefit profiles of radiation treatment in older patients and more accurately quantify treatment efficacy in this group.


Nearly half of all women diagnosed with breast or ovarian cancer are age 65 years or older with the number of women diagnosed expected to increase as the population ages and life expectancy improves. Older women are less likely to be offered standard cancer treatments, are more likely to develop higher toxicity, and have higher mortality. Chronologic age should not be the only factor used for making treatment decisions. Functional dependence, organ function, comorbidity, polypharmacy, social support, cognitive and/or psychosocial factors, overall life expectancy, and patient’s goals of care are equally vital and should be assessed before and during treatment. In this review, current evidence and treatment guidelines for older women with breast or ovarian cancer are outlined.



Over the last 50 years, major improvements have been made in our understanding of the driving forces, both parallel and opposing, that lead to aging and cancer. Many theories on aging first proposed in the 1950s, including those associated with telomere biology, senescence, and adult stem-cell regulation, have since gained support from cumulative experimental evidence. These views suggest that the accumulation of mutations might be a common driver of both aging and cancer. Moreover, some tumor suppressor pathways lead to aging in line with the theory of antagonist pleiotropy. According to the evolutionary-selected disposable soma theory, aging should affect primarily somatic cells. At the cellular level, both intrinsic and extrinsic pathways regulate aging and senescence. However, increasing lines of evidence support the hypothesis that these driving forces might be regulated by evolutionary-conserved pathways that modulate energy balance. According to the hyperfunction theory, aging is a quasi-program favoring both age-related diseases and cancer that could be inhibited by the regulation of longevity pathways. This review summarizes these hypotheses, as well as the experimental data that have accumulated over the last 60 years linking aging and cancer.


Purpose

The aging of the population is a real concern for surgical oncologists, who are increasingly being asked to treat patients who would not have been considered for surgery in the past. In many cases, decisions are made with relatively little evidence, most of which was derived from trials in which older age was a limiting factor for recruitment.

Methods

This review focuses on risk assessment and perioperative management. It describes the relationship between age and outcomes for colon, lung, hepatobiliary, and head and neck cancer, which are predominantly diseases of the elderly and are a major cause of morbidity and mortality.

Results

Effective surgery requires safe performance as well as reasonable postoperative life expectancy and maintenance of quality of life. Treatment decisions for potentially vulnerable elderly patients should take into account data obtained from the evaluation of geriatric syndromes, such as frailty, functional and cognitive limitations, malnutrition, comorbidities, and polypharmacy, as well as social support. Postoperative care should include prevention and treatment of complications seen more frequently in the elderly, including postoperative delirium, functional decline, and the need for institutionalization.

Conclusion

Surgery remains the best modality for treatment of solid tumors, and chronologic age alone should not be a determinant for treatment decisions. With adequate perioperative risk stratification, functional assessment, and oncologic prognostication, elderly patients with cancer can do as well in terms of morbidity and mortality as their younger counterparts. If surgery is determined to be the appropriate treatment modality, patients should not be denied this option because of their age.


Population studies support an increased incidence of most cancers among older adults. Colorectal cancer has high prevalence in the aging population, with a median age of 69 years at diagnosis and 74 years at death. The vast majority of patients with colon cancer (CC) will require chemotherapy treatments during their disease course, challenging oncologists with the task of tailoring therapy for older patients with CC in the face of limited evidence-based data to guide them. Factors such as comorbidity, performance status, cognitive function, and social support may affect decision making and complicate tolerance of any recommended therapy. In recent years, attention to the specific needs of the aging population with cancer has given rise to the field of geriatric oncology in general, and has generated an increasing fund of knowledge on which to base chemotherapy delivery for this specific population of patients with CC. This article will review the available data specifically for chemotherapy management of older patients with CC in the postoperative and metastatic settings.


The challenge in treating the older adult with cancer is accurately accounting for and adapting management to the heterogeneity in health status of the individual patient. Many oncologists recognize that chronological age alone should not be the determinant when deciding on a treatment regimen. Easily measurable markers that provide an assessment of functional age would be ideal to assess frailty, which may predispose the patient to complications from cancer treatment, including increased toxicity, functional decline, decreased quality of life, and poorer survival. Several categories of potential markers, including chronic inflammatory markers, markers of cellular senescence, and imaging to assess muscle mass to detect sarcopenia, may provide insight into the likelihood of treatment-related complications. This article discusses candidate markers and strategies to evaluate these markers in cancer treatment trials, with the aim of developing a method to assess risk of oncologic outcomes and guide management decisions for both the physician and patient.


The introduction of targeted therapy has ushered in the era of personalized medicine in cancer therapy. The increased understanding of tumor heterogeneity has led to the determination of specific targets that can be exploited in treatment. This review highlights approved drugs in different therapeutic classes, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, drugs targeted to the human epidermal growth factor receptor 2, BRAF-mutation targeted drugs, anti–epidermal growth factor receptor inhibitors, and anti-vascular endothelial growth factor therapy. There have not been elderly patient–specific trials of these therapies. Most of the data are extrapolated from larger trials in which older patients generally were a fraction of the participants. Therapeutic recommendations are made on the basis of this analysis with the recognition that the older clinical trial participants may not be representative of patients seen in daily practice. Patient selection and geriatric evaluation are critical for appropriate drug selection, dosing, and monitoring. With care, these therapies are a major step forward in the safe and effective treatment of older patients with cancer.


The treatment of cancer presents specific concerns that are unique to the growing demographic of elderly patients. Because the incidence of cancer is strongly correlated with aging, the expansion of supportive care and other age-appropriate therapies will be of great importance as the population of elderly patients with cancer increases in the coming years.

Elderly patients are especially likely to experience febrile neutropenia, complications from chemotherapy-induced nausea, anemia, osteoporosis (especially in patients diagnosed with breast or prostate cancer), depression, insomnia, and fatigue. These issues are often complicated by other chronic conditions related to age, such as diabetes and cardiac disease.

For many patients, symptoms may be addressed both through lifestyle management and pharmaceutical approaches. Therefore, the key to improving quality of life for the elderly patient with cancer is an awareness of their specific needs and a familiarity with emergent treatment options.



Purpose

Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable.

Methods

We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis.

Results

Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v 13%, respectively; P = .030) and systemic recurrence (19% v 29%, respectively; P = .027) and improved Mandard tumor regression scores (P < .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation.

Conclusion

The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.



Lung cancer is a disease of the elderly. In older patients, the management of a malignancy as complex and potentially as lethal as lung cancer is challenging. Despite the fact that a large proportion of patients with non–small-cell lung cancer are elderly, information remains scant on how best to treat these patients. The goal of this review is to discuss the published literature and to provide guidance on how to treat elderly patients within three broad stages: (1) metastatic cancer, (2) early-stage cancer after surgery, and (3) locally advanced inoperable cancer. Because decisions on how and when to prescribe systemic treatment can be particularly difficult, this review focuses heavily on chemotherapy-related treatment decisions with some discussion of emerging data on the use of the comprehensive geriatric assessment.



The US population of cancer survivors age ≥ 65 years will continue to grow rapidly over the next few decades. This growth will be driven largely by the aging of the national population. With the diffusion of earlier detection and more effective therapies, the majority of these individuals can expect to live long term after diagnosis. This often vulnerable group of survivors poses significant challenges for both researchers and clinicians with regard to how best to document and address its unique health care needs. In this article, we briefly review the long-term and late-occurring effects of cancer and its treatment in older survivors, review information on current patterns of post-treatment care and the evolving guidelines for this care, and discuss opportunities for future research.


Cancer incidence increases with age, and as life expectancy increases, the number of elderly patients with cancer is increasing. Cancer treatments, including chemotherapy and radiotherapy, have significant short- and long-term effects on cardiovascular function. These cardiotoxic effects can be acute, such as changes in electrocardiogram (ECG), arrhythmias, ischemia, and pericarditis and/or myocarditis-like syndromes, or they can be chronic, such as ventricular dysfunction. Anticancer therapies can also have indirect effects, such as alterations in blood pressure, or can cause metabolic abnormalities that subsequently increase risk for cardiac events. In this review, we explore both observational and clinical trial evidence of cardiac risk in the elderly. In both observational and clinical trial data, risk of cardiotoxicity with anthracycline-based chemotherapy increases with age. However, it is less clear whether the association between age and cardiotoxicity exists for newer treatments. The association may not be well demonstrated as a result of under-representation of elderly patients in clinical trials and avoidance of these therapies in this population. In addition, we discuss strategies for surveillance and prevention of cardiotoxicity in the elderly. In the elderly, it is important to be aware of the potential for cardiotoxicity during long-term follow-up and to consider both prevention and surveillance of these late effects.


Purpose

Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG).

Patients and Methods

Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified.

Results

The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P =.01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS.

Conclusion

In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.


A majority of cancer diagnoses and deaths occur in patients age ≥ 65 years. With the aging of the US population, the number of older adults with cancer will grow. Although the coming wave of older patients with cancer was anticipated in the early 1980s, when the need for more research on the cancer-aging interface was recognized, many knowledge gaps remain when it comes to treating older and/or frailer patients with cancer. Relatively little is known about the best way to balance the risks and benefits of existing cancer therapies in older patients; however, these patients continue to be underrepresented in clinical trials. Furthermore, the available clinical trials often do not include end points pertinent to the older adult population, such as preservation of function, cognition, and independence. As part of its ongoing effort to advance research in the field of geriatric oncology, the Cancer and Aging Research Group held a conference in November 2012 in collaboration with the National Cancer Institute, the National Institute on Aging, and the Alliance for Clinical Trials in Oncology. The goal was to develop recommendations and establish research guidelines for the design and implementation of therapeutic clinical trials for older and/or frail adults. The conference sought to identify knowledge gaps in cancer clinical trials for older adults and propose clinical trial designs to fill these gaps. The ultimate goal of this conference series is to develop research that will lead to evidence-based care for older and/or frail adults with cancer.


Purpose

To estimate the antitumor activity of pemetrexed and cisplatin with objective tumor response (partial and complete) in patients with advanced, persistent, or recurrent carcinoma of the cervix and to determine the nature and degree of toxicity of this regimen. Secondarily, this study will determine the effects of this regimen on progression-free survival and overall survival.

Patients and Methods

Eligible, consenting patients received pemetrexed 500 mg/m2 and cisplatin 50 mg/m2 intravenously repeated every 21 days until disease progression or adverse events prohibited further therapy. Patients received no prior therapeutic chemotherapy, except when administered concurrently with primary radiation therapy. Subsequent doses were adjusted according to observed toxicity and protocol guidelines. Adverse events were assessed with Common Terminology Criteria for Adverse Events v 3.0. The primary measure of efficacy was tumor response according to Response Evaluation Criteria in Solid Tumors. The study was stratified by prior radiation therapy.

Results

From September 2008 to November 2011, 55 patients were enrolled by five Gynecologic Oncology Group member institutions; of those, 54 patients were eligible and assessable. The regimen was well tolerated with 26% receiving more than nine cycles. The most common greater than grade 2 toxicities were neutropenia 35%, leukopenia 28%, and metabolic 28%. The overall response rate was 31% (one complete and 16 partial). The median progression-free survival was 5.7 months, and overall survival was 12.3 months.

Conclusion

Pemetrexed in combination with cisplatin demonstrates activity in the treatment of advanced, persistent, or recurrent carcinoma of the cervix.


Purpose

To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer.

Methods

SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment–related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care.

Results

GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensity. The panel recommended that the following domains be evaluated in a GA: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and presence of geriatric syndromes. Although several combinations of tools and various models are available for implementation of GA in oncology practice, the expert panel could not endorse one over another.

Conclusion

There is mounting data regarding the utility of GA in oncology practice; however, additional research is needed to continue to strengthen the evidence base.


Purpose

In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution.

Methods

We analyzed ALK mutations in 54 paired diagnosis–relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was observed in one paired sample, a minor mutated component in the other sample was searched for by more than 100,000x deep sequencing of the relevant hotspot, with a sensitivity of 0.17%.

Results

All nine ALK-mutated cases at diagnosis demonstrated the same mutation at relapse, in one case in only one of several relapse nodules. In five additional cases, the mutation seemed to be relapse specific, four of which were investigated by deep sequencing. In two cases, no mutation evidence was observed at diagnosis. In one case, the mutation was present at a subclonal level (0.798%) at diagnosis, whereas in another case, two different mutations resulting in identical amino acid changes were detected, one only at diagnosis and the other only at relapse. Further evidence of clonal evolution of ALK-mutated cells was provided by establishment of a fully ALK-mutated cell line from a primary sample with an ALK-mutated cell population at subclonal level (6.6%).

Conclusion

In neuroblastoma, subclonal ALK mutations can be present at diagnosis with subsequent clonal expansion at relapse. Given the potential of ALK-targeted therapy, the significant spatiotemporal variation of ALK mutations is of utmost importance, highlighting the potential of deep sequencing for detection of subclonal mutations with a sensitivity 100-fold that of Sanger sequencing and the importance of serial samplings for therapeutic decisions.


Purpose

The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non–small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population.

Methods

Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment.

Results

Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS).

Conclusion

In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.


Purpose

Deregulation of key PI3K/AKT pathway genes may contribute to endocrine resistance in breast cancer (BC). PIK3CA is the most frequently mutated gene in luminal BC (~ 35%); however, the effect of mutations in helical versus kinase domains remains controversial. We hypothesize that improved outcomes occur in patients with estrogen receptor–positive (ER positive) BC receiving endocrine therapy and possessing PIK3CA mutations.

Materials and Methods

DNA was extracted from 4,540 formalin-fixed paraffin-embedded BC samples from the Exemestane Versus Tamoxifen-Exemestane pathology study. Mutational analyses were performed for 25 mutations (PIK3CAx10, AKT1x1, KRASx5, HRASx3, NRASx2 and BRAFx4).

Results

PIK3CA mutations were frequent (39.8%), whereas RAS/RAF mutations were rare (< 1%). In univariable analyses PIK3CA mutations were associated with significantly improved 5-year distant relapse-free survival (DRFS; HR, 0.76; 95% CI, 0.63 to 0.91; P = .003). However, a multivariable analysis correcting for known clinical and biologic prognostic factors failed to demonstrate that PIK3CA mutation status is an independent prognostic marker for DRFS (HR, 0.92; 95% CI, 0.75 to 1.12; P = .4012). PIK3CA mutations were more frequent in low-risk luminal BCs (eg, grade 1 node v 3, node-negative v -positive), confounding the relationship between mutations and outcome.

Conclusion

PIK3CA mutations are present in approximately 40% of luminal BCs but are not an independent predictor of outcome in the context of endocrine therapy, whereas RAS/RAF mutations are rare in luminal BC. A complex relationship between low-risk cancers and PIK3CA mutations was identified. Although the PI3K/AKT pathway remains a viable therapeutic target as the result of a high mutation frequency, PIK3CA mutations do not seem to affect residual risk following treatment with endocrine therapy.


Purpose

Poor and underserved women face barriers in receiving timely and appropriate breast cancer care. Patient navigators help individuals overcome these barriers, but little is known about whether patient navigation improves quality of care. The purpose of this study is to examine whether navigated women with breast cancer are more likely to receive recommended standard breast cancer care.

Patients and Methods

Women with breast cancer who participated in the national Patient Navigation Research Program were examined to determine whether the care they received included the following: initiation of antiestrogen therapy in patients with hormone receptor–positive breast cancer; initiation of postlumpectomy radiation therapy; and initiation of chemotherapy in women younger than age 70 years with triple-negative tumors more than 1 cm. This is a secondary analysis of a multicenter quasi-experimental study funded by the National Cancer Institute to evaluate patient navigation. Multiple logistic regression was performed to compare differences in receipt of care between navigated and non-navigated participants.

Results

Among participants eligible for antiestrogen therapy, navigated participants (n = 380) had a statistically significant higher likelihood of receiving antiestrogen therapy compared with non-navigated controls (n = 381; odds ratio [OR], 1.73; P = .004) in a multivariable analysis. Among the participants eligible for radiation therapy after lumpectomy, navigated participants (n = 255) were no more likely to receive radiation (OR, 1.42; P = .22) than control participants (n = 297).

Conclusion

We demonstrate that navigated participants were more likely than non-navigated participants to receive antiestrogen therapy. Future studies are required to determine the full impact patient navigation may have on ensuring that vulnerable populations receive quality care.


Purpose

Negative [18F]fluorodeoxyglucose (FDG) –positron emission tomography (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative predictive value would be even higher in patients responding rapidly enough to be PET negative after one cycle. This prospective study aimed to assess the prognostic value of PET after one cycle of chemotherapy in HL and to assess the dynamics of FDG uptake after one cycle (PET1) and after two cycles (PET2).

Patients and Methods

All PET scans were read by two blinded, independent reviewers in different countries, according to the Deauville five-point scale. The main end point was progression-free survival (PFS) after 2 years.

Results

A total of 126 patients were included, and all had PET1; 89 patients had both PET1 and PET2. The prognostic value of PET1 was statistically significant with respect to both PFS and overall survival. Two-year PFS for PET1-negative and PET1-positive patients was 94.1% and 40.8%, respectively. Among those with both PET1 and PET2, 2-year PFS was 98.3% and 38.5% for PET1-negative and PET1-positive patients and 90.2% and 23.1% for PET2-negative and PET2-positive patients, respectively. No PET1-negative patient was PET2 positive.

Conclusion

PET after one cycle of chemotherapy is highly prognostic in HL. No other prognostic tool identifies a group of patients with HL with a more favorable outcome than those patients with a negative PET1. In the absence of precise pretherapeutic predictive markers, PET1 is the best method for response-adapted strategies designed to select patients for less intensive treatment.






Purpose

To evaluate the career plans, professional expectations, and well-being of oncology fellows compared with actual experiences of practicing oncologists.

Methods

US oncology fellows taking the 2013 Medical Oncology In-Training Examination (MedOnc ITE) were invited to participate in an optional postexamination survey. The survey evaluated fellows’ career plans and professional expectations and measured burnout, quality of life (QOL), fatigue, and satisfaction with work-life balance (WLB) using standardized instruments. Fellows’ professional expectations and well-being were compared with actual experiences of US oncologists assessed simultaneously.

Results

Of the 1,637 oncology fellows in the United States, 1,373 (83.9%) took the 2013 MedOnc ITE. Among these, 1,345 (97.9%) completed the postexamination survey. The frequency of burnout among fellows decreased from 43.3% in year 1 to 31.7% in year 2 and 28.1% in year 3 (P < .001). Overall, the rate of burnout among fellows and practicing oncologists was similar (34.1% v 33.7%; P = .86). With respect to other dimensions of well-being, practicing oncologists had lower fatigue (P < .001) and better overall QOL scores (P < .001) than fellows but were less satisfied with WLB (P = .0031) and specialty choice (P < .001). Fellows’ expectations regarding future work hours were 5 to 6 hours per week fewer than oncologists’ actual reported work hours. Levels of burnout (P = .02) and educational debt (P ≤ .004) were inversely associated with ITE scores. Fellows with greater educational debt were more likely to pursue private practice and less likely to plan an academic career.

Conclusion

Oncology fellows entering practice trade one set of challenges for another. Unrealized expectations regarding work hours may contribute to future professional dissatisfaction, burnout, and challenges with WLB.