Showing papers in "Oncologist in 2013"
TL;DR: Insured patients undergoing cancer treatment and seeking copayment assistance experience considerable subjective financial burden, and they may alter their care to defray out-of-pocket expenses.
Abstract: Purpose.
Cancer patients carry rising burdens of health care-related out-of-pocket expenses, and a growing number of patients are considered “underinsured.” Our objective was to describe experiences of insured cancer patients requesting copayment assistance and to describe the impact of health care expenses on well-being and treatment.
796 citations
TL;DR: Application of the NOMS paradigm integrates multimodality therapy to optimize local tumor control, pain relief, and restoration or preservation of neurologic function and minimizes morbidity in this often systemically ill patient population.
Abstract: Background.
Spinal metastases frequently arise in patients with cancer. Modern oncology provides numerous treatment options that include effective systemic, radiation, and surgical options. We delineate and provide the evidence for the neurologic, oncologic, mechanical, and systemic (NOMS) decision framework, which is used at Memorial Sloan-Kettering Cancer Center to determine the optimal therapy for patients with spine metastases.
523 citations
TL;DR: The results suggest that future clinical trials focused on TN disease should consider stratifying patients based upon BL versus non-BL gene expression profiles, which appears to be the main biological difference seen in patients with TN breast cancer.
Abstract: Triple-negative (TN) and basal-like (BL) breast cancer definitions have been used interchangeably to identify breast cancers that lack expression of the hormone receptors and overexpression and/or amplification of HER2. However, both classifications show substantial discordance rates when compared to each other. Here, we molecularly characterize TN tumors and BL tumors, comparing and contrasting the results in terms of common patterns and distinct patterns for each. In total, when testing 412 TN and 473 BL tumors, 21.4% and 31.5% were identified as non-BL and non-TN, respectively. TN tumors identified as luminal or HER2-enriched (HER2E) showed undistinguishable overall gene expression profiles when compared versus luminal or HER2E tumors that were not TN. Similar findings were observed within BL tumors regardless of their TN status, which suggests that molecular subtype is preserved regardless of individual marker results. Interestingly, most TN tumors identified as HER2E showed low HER2 expression and lacked HER2 amplification, despite the similar overall gene expression profiles to HER2E tumors that were clinically HER2-positive. Lastly, additional genomic classifications were examined within TN and BL cancers, most of which were highly concordant with tumor intrinsic subtype. These results suggest that future clinical trials focused on TN disease should consider stratifying patients based upon BL versus non-BL gene expression profiles, which appears to be the main biological difference seen in patients with TN breast cancer.
495 citations
TL;DR: Patients with either ROS1 or RET rearrangements appear to have unique clinical and pathologic features that may facilitate identification and enrichment strategies, and this finding suggests that both ROS1 and RET are independent oncogenic drivers that may be viable therapeutic targets.
Abstract: The discovery of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) has stimulated renewed interest in oncogenic fusions as potential therapeutic targets. Recently, genetic alterations in ROS1 and RET were identified in patients with NSCLC. Like ALK, genetic alterations in ROS1 and RET involve chromosomal rearrangements that result in the formation of chimeric fusion kinases capable of oncogenic transformation. Notably, ROS1 and RET rearrangements are rarely found with other genetic alterations, such as EGFR, KRAS, or ALK. This finding suggests that both ROS1 and RET are independent oncogenic drivers that may be viable therapeutic targets. In initial screening studies, ROS1 and RET rearrangements were identified at similar frequencies (approximately 1%-2%), using a variety of genotyping techniques. Importantly, patients with either ROS1 or RET rearrangements appear to have unique clinical and pathologic features that may facilitate identification and enrichment strategies. These features may in turn expedite enrollment in clinical trials evaluating genotype-directed therapies in these rare patient populations. In this review, we summarize the molecular biology, clinical features, detection, and targeting of ROS1 and RET rearrangements in NSCLC.
285 citations
TL;DR: Immune-related adverse events (irAEs) are important to recognize early, and their presentation, timing of onset, and general recommendations for workup and management will be reviewed.
Abstract: The treatment for metastatic melanoma has evolved significantly in the past few years. Ipilimumab, an immunotherapy, is now in mainstream oncology practice given that it has shown improved overall survival in randomized clinical trials. Other immune modulating agents, such as programmed death receptor-1 and programmed death receptor ligand-1 antibodies, are showing promise in early clinical trials. This manuscript will review ipilimumab and its most common side effects. Immune-related adverse events (irAEs) are important to recognize early, and their presentation, timing of onset, and general recommendations for workup and management will be reviewed. Assembling a multidisciplinary team, as well as thorough education of the patient, is recommended to optimize patient care.
273 citations
TL;DR: The use of FOLFIRINOX was associated with conversion to resectability in >20% of patients and the toxicities observed with the use of this regimen raise important questions about how to best treat patients with LAPC.
Abstract: The objective of our retrospective institutional experience is to report the overall response rate, R0 resection rate, progression-free survival, and safety/toxicity of neoadjuvant FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and chemoradiation in patients with locally advanced pancreatic cancer (LAPC). Patients with LAPC treated with FOLFIRINOX were identified via the Massachusetts General Hospital Cancer Center pharmacy database. Demographic information, clinical characteristics, and safety/tolerability data were compiled. Formal radiographic review was performed to determine overall response rates (ORRs). Twenty-two patients with LAPC began treatment with FOLFIRINOX between July 2010 and February 2012. The ORR was 27.3%, and the median progression-free survival was 11.7 months. Five of 22 patients were able to undergo R0 resections following neoadjuvant FOLFIRINOX and chemoradiation. Three of the five patients have experienced distant recurrence within 5 months. Thirty-two percent of patients required at least one emergency department visit or hospitalization while being treated with FOLFIRINOX. FOLFIRINOX possesses substantial activity in patients with LAPC. The use of FOLFIRINOX was associated with conversion to resectability in >20% of patients. However, the recurrences following R0 resection in three of five patients and the toxicities observed with the use of this regimen raise important questions about how to best treat patients with LAPC.
252 citations
TL;DR: The use of bevacizumab with chemotherapy resulted in statistically significant increases in OS and PFS for patients with mCRC, and the PFS benefit extended across the clinically relevant subgroups examined.
Abstract: Purpose.
This analysis pooled individual patient data from randomized controlled trials (RCTs) to more thoroughly examine clinical outcomes when adding bevacizumab to chemotherapy for patients with metastatic colorectal cancer (mCRC).
214 citations
TL;DR: A concise drug review summarizes the current state of treatment with azacitidine and decitabine in patients with higher-risk myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia who are ineligible for more intensive treatments.
Abstract: The introduction of the hypomethylating agents azacitidine and decitabine has been a major advancement in the treatment of patients with higher-risk myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia who are ineligible for more intensive treatments. This concise drug review summarizes the current state of treatment with azacitidine and decitabine.
214 citations
TL;DR: Dermatologic AEs associated with vemurafenib treatment in patients with melanoma were generally manageable with supportive care measures.
Abstract: Background.
Vemurafenib has been approved for the treatment of patients with advanced BRAFV600E-mutant melanoma. This report by the Vemurafenib Dermatology Working Group presents the characteristics of dermatologic adverse events (AEs) that occur in vemurafenib-treated patients, including cutaneous squamous cell carcinoma (cuSCC).
201 citations
TL;DR: Recognition that variation in cancer care quality may be correlated with race (and socioeconomic and health system factors) may assist policy makers in identifying strategies to more equally distribute clinical expertise and health infrastructure across multiple user populations.
Abstract: Racial disparities in breast cancer mortality have been widely documented for several decades and persist despite advances in receipt of mammography across racial groups. This persistence leads to questions about the roles of biological, social, and health system determinants of poor outcomes. Cancer outcomes are a function not only of innate biological factors but also of modifiable characteristics of individual behavior and decision making as well as characteristics of patient-health system interaction and the health system itself. Attempts to explain persistent racial disparities have mostly been limited to discussion of differences in insurance coverage, socioeconomic status, tumor stage at diagnosis, comorbidity, and molecular subtype of the tumor. This article summarizes existing literature exploring reasons for racial disparities in breast cancer mortality, with an emphasis on treatment disparities and opportunities for future research. Because breast cancer care requires a high degree of multidisciplinary team collaboration, ensuring that guideline recommended treatment (such as endocrine therapy for hormone receptor positive patients) is received by all racial/ethnic groups is critical and requires coordination across multiple providers and health care settings. Recognition that variation in cancer care quality may be correlated with race (and socioeconomic and health system factors) may assist policy makers in identifying strategies to more equally distribute clinical expertise and health infrastructure across multiple user populations.
199 citations
TL;DR: Those undergoing chemotherapy as outpatients are at increased risk for venous thromboembolism and for major bleeding complications and thromboprophylaxis may be considered for such patients after carefully assessing the risks and benefits of treatment.
Abstract: Introduction.
The occurrence of malignant disease increases the risk for venous thromboembolism (VTE). Here we evaluate the risk for VTE in a large unselected cohort of patients with cancer receiving chemotherapy.
TL;DR: High-dose itraconazole (600 mg/day) has modest antitumor activity in men with metastatic CRPC that is not mediated by testosterone suppression.
Abstract: BACKGROUND The antifungal drug itraconazole inhibits angiogenesis and Hedgehog signaling and delays tumor growth in murine prostate cancer xenograft models. We conducted a noncomparative, randomized, phase II study evaluating the antitumor efficacy of two doses of oral itraconazole in men with metastatic prostate cancer. PATIENTS AND METHODS We randomly assigned 46 men with chemotherapy-naive metastatic castration-resistant prostate cancer (CRPC) to receive low-dose (200 mg/day) or high-dose (600 mg/day) itraconazole until disease progression or unacceptable toxicity. The primary endpoint was the prostate-specific antigen (PSA) progression-free survival (PPFS) rate at 24 weeks; a 45% success rate in either arm was prespecified as constituting clinical significance. Secondary endpoints included the progression-free survival (PFS) rate and PSA response rate (Prostate Cancer Working Group criteria). Exploratory outcomes included circulating tumor cell (CTC) enumeration, serum androgen measurements, as well as pharmacokinetic and pharmacodynamic analyses. RESULTS The high-dose arm enrolled to completion (n = 29), but the low-dose arm closed early (n = 17) because of a prespecified futility rule. The PPFS rates at 24 weeks were 11.8% in the low-dose arm and 48.0% in the high-dose arm. The median PFS times were 11.9 weeks and 35.9 weeks, respectively. PSA response rates were 0% and 14.3%, respectively. In addition, itraconazole had favorable effects on CTC counts, and it suppressed Hedgehog signaling in skin biopsy samples. Itraconazole did not reduce serum testosterone or dehydroepiandrostenedione sulfate levels. Common toxicities included fatigue, nausea, anorexia, rash, and a syndrome of hypokalemia, hypertension, and edema. CONCLUSION High-dose itraconazole (600 mg/day) has modest antitumor activity in men with metastatic CRPC that is not mediated by testosterone suppression.
TL;DR: This review summarizes the current literature surrounding RAS and discusses its potential as a diagnostic and prognostic indicator in the management of thyroid cancer.
Abstract: In recent years, our understanding of the genetic alterations underlying thyroid oncogenesis has greatly expanded. The use of molecular markers, including RAS, in the management of thyroid carcinoma is also increasing. This review summarizes the current literature surrounding RAS and discusses its potential as a diagnostic and prognostic indicator in the management of thyroid cancer.
TL;DR: Her2/neu positivity and treatment with trastuzumab correlated well with long-term survival and response in patients with SDCs and it is proposed that HER2/ NEu status be examined routinely in all patients withSDCs.
Abstract: Objective Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with high mortality and poor response to treatment. A significant fraction of SDCs are HER2 positive. This retrospective review examines HER2 testing in SDC and the outcome of trastuzumab-based therapy in adjuvant and palliative settings. Methods A total of 13 patients with SDC and HER2/neu expression by immunohistochemistry of 1-3+ were treated with trastuzumab in adjuvant (n = 8) or palliative (n = 5) setting. Adjuvant therapy consisted of concurrent radiation and chemotherapy with weekly paclitaxel, carboplatin, and trastuzumab (TCH) for 6 weeks followed by TCH for 12 weeks and trastuzumab alone for 1 year. Palliative treatment for metastatic disease consisted of TCH every 3 weeks for 6 cycles followed by trastuzumab for variable time periods with or without second-line chemotherapy for progression. All patients had fluorescence in situ hybridization testing for HER2/neu gene amplification. Results The median duration of follow-up was 27 months (range: 8-48 months). In all, 62% of adjuvant patients (5/8) had no evidence of disease more than 2 years from completion of therapy. All patients with metastatic disease (5/5 patients) responded to treatment with TCH. One patient achieved a complete response and remains with no evidence of disease 52 months after initiation of TCH. The median duration of response was 18 months (range: 8-52 months). Conclusion HER2/neu positivity and treatment with trastuzumab correlated well with long-term survival and response in our patients. Based on this data, we propose that HER2/neu status be examined routinely in all patients with SDCs and the treatment be directed accordingly.
TL;DR: These results suggest that metformin is the drug of choice in the treatment of patients with cancer and concurrent type 2 diabetes.
Abstract: UNLABELLED Patients with type 2 diabetes have increased cancer risk and cancer-related mortality, which can be reduced by metformin treatment. However, it is unclear whether metformin can also modulate clinical outcomes in patients with cancer and concurrent type 2 diabetes. PATIENTS AND METHODS A meta-analysis of 20 publications that included 13,008 subjects was performed to investigate the association between metformin and overall survival (OS) as well as cancer-specific survival (CSS) in patients with cancer and concurrent type 2 diabetes. RESULTS We found that there was a relative survival benefit associated with metformin treatment compared with treatment with other glucose-lowering medications in both OS and CSS (hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.55-0.79 and HR = 0.62; 95% CI: 0.46-0.84, respectively). These associations were also observed in subgroups by cancer type and country. CONCLUSION These results suggest that metformin is the drug of choice in the treatment of patients with cancer and concurrent type 2 diabetes.
TL;DR: The combination of pertuzumab plus trastuzumAB plus docetaxel did not increase the incidence of cardiac adverse events, including LVSD, compared with the control arm in HER2-positive MBC, and the majority of heart adverse events were reversible.
Abstract: INTRODUCTION We report cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel observed in the phase III study CLEOPATRA in patients with HER2-positive first-line metastatic breast cancer (MBC). PATIENTS AND METHODS Left ventricular ejection fraction (LVEF) ≥ 50% and ECOG performance status of 0 or 1 were required for study entry. During the study, LVEF assessments took place every 9 weeks. Pertuzumab/placebo was given at 840 mg, then 420 mg q3w; trastuzumab was administered at 8 mg/kg, then 6 mg/kg q3w, and docetaxel was initiated at 75 mg/m(2) q3w. RESULTS The incidence of cardiac adverse events (all grades) was 16.4% in the placebo arm and 14.5% in the pertuzumab arm, with left ventricular systolic dysfunction (LVSD, all grades) being the most frequently reported event (8.3% versus 4.4% in the placebo and pertuzumab arm). Declines in LVEF by ≥ 10% points from baseline and to <50% were reported in 6.6% and 3.8% of patients in the placebo and pertuzumab arm, respectively. Seventy-two percent (placebo arm) and 86.7% (pertuzumab arm) of those patients recovered to a value ≥ 50%. The incidence of symptomatic LVSD was low, occurring in 1.8% (n = 7) versus 1.0% (n = 4) of patients in the placebo and pertuzumab arm. In 8/11 patients, the symptomatic LVSD had resolved at data cutoff. CONCLUSION The combination of pertuzumab plus trastuzumab plus docetaxel did not increase the incidence of cardiac adverse events, including LVSD, compared with the control arm in HER2-positive MBC. The majority of cardiac adverse events were reversible.
TL;DR: A multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab found several patients demonstrated serologic responses to cancer-testis antigens and other antIGens, but the overall response rate was low.
Abstract: The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8-26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma.
TL;DR: The burden of breast cancer in the region is considerable and growing due to demographic changes, particularly the aging population, and socioeconomic development, as well as the challenges and opportunities for improvement.
Abstract: This review presents an overview of breast cancer care, burden, and outcomes in Latin America, as well as the challenges and opportunities for improvement. Information was gleaned through a review of the literature, public databases, and conference presentations, in addition to a survey of clinical experts and patient organizations from the region. Breast cancer annual incidence (114,900 cases) and mortality (37,000 deaths) are the highest of all women's cancers in Latin America, and they are increasing. Twice as many breast cancer deaths are expected by 2030. In Peru, Mexico, Colombia, and Brazil, diagnosis and death at younger ages deprives society of numerous productive years, as does high disease occurrence in Argentina and Uruguay. Approximately 30%–40% of diagnoses are metastatic disease. High mortality-to-incidence ratios (MIRs) in Latin America indicate poor survival, partly because of the late stage at diagnosis and poorer access to treatment. Between 2002 and 2008, MIRs decreased in all countries, albeit unevenly. Costa Rica's change in MIR outpaced incidence growth, indicating impressive progress in breast cancer survival. The situation is similar, although to a lesser extent, in Colombia and Ecuador. The marginal drops of MIRs in Brazil and Mexico mainly reflect incidence growth rather than progress in outcomes. Panama's MIR is still high. Epidemiological data are scattered and of varying quality in Latin America. However, one could ascertain that the burden of breast cancer in the region is considerable and growing due to demographic changes, particularly the aging population, and socioeconomic development. Early diagnosis and population-wide access to evidence-based treatment remain unresolved problems, despite progress achieved by some countries.
TL;DR: This is the first study, to the authors' knowledge, to demonstrate that continuation of EGFR TKI with chemotherapy in patients with acquired resistance improves outcomes compared with chemotherapy alone, and an improved response rate but no difference in progression-free survival or overall survival.
Abstract: Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer has an oncogene-addicted biology that confers sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Published data suggest that EGFR addiction persists after development of TKI acquired resistance, leading many clinicians to continue TKI with subsequent chemotherapy; however, this strategy has not been formally evaluated. Methods. We retrospectively reviewed an institutional database to identify patients with advanced EGFR mutation with acquired resistance who subsequently received chemotherapy. Patients were classified as receiving chemotherapy with continued erlotinib or chemotherapy alone. We assessed differences in outcomes between the two strategies. Results. Seventy-eight patients were included, 34 treated with chemotherapy and erlotinib and 44 treated with chemotherapy alone. Objective response rate was evaluable in 57 patients and was 41% for those treated with chemotherapy and erlotinib and 18% for those treated with chemotherapy alone. After adjusting for chemotherapy regimen and length of initial TKI course, the odds ratio for the response rate was 0.20 (95% confidence interval: 0.05-0.78; p = .02) favoring treatment with chemotherapy and erlotinib. The median progression-free survival was 4.4 months on chemotherapy and erlotinib and 4.2 months on chemotherapy alone (adjusted hazard ratio = 0.79; 95% confidence interval: 0.48-1.29; p = .34). There was no difference in overall survival. Conclusion. This is the first study, to our knowledge, to demonstrate that continuation of EGFR TKI with chemotherapy in patients with acquired resistance improves outcomes compared with chemotherapy alone. We observed an improved response rate but no difference in progression-free survival or overall survival. A larger prospective clinical trial is needed to evaluate this promising strategy further.
TL;DR: Adequate evidence excludes an overall excess cancer risk in TZD users within a few years after starting treatment, however, there is a modest excess risk of bladder cancer, particularly with reference to pioglitazone.
Abstract: Objective.
To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies.
TL;DR: The results show that the majority of cancer symptoms are associated with inflammation, and the strength of the potential relationship between systemic inflammation and common cancer symptoms should be examined further within the context of an anti-inflammatory intervention trial.
Abstract: Introduction Inflammation has been identified as a hallmark of cancer and may be necessary for tumorgenesis and maintenance of the cancer state. Inflammation-related symptoms are common in those with cancer; however, little is known about the relationship between symptoms and systemic inflammation in cancer. The aim of the present study was to examine the relationship between symptoms and systemic inflammation in a large cohort of patients with advanced cancer. Methods Data from an international cohort of patients with advanced cancer were analyzed. Symptoms and patient-related outcomes were recorded using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire--Core Questionnaire. Systemic inflammation was assessed using C-reactive protein levels. The relationship between these symptoms and systemic inflammation was examined using Spearman rank correlation (ρ) and the Mann-Whitney U test. Results Data were available for 1,466 patients across eight European countries; 1,215 patients (83%) had metastatic disease at study entry. The median survival was 3.8 months (interquartile range [IQR] 1.3-12.2 months). The following were associated with increased levels of inflammation: performance status (ρ = .179), survival (ρ = .347), pain (ρ = .154), anorexia (ρ = .206), cognitive dysfunction (ρ = .137), dyspnea (p= .150), fatigue (ρ = .197), physical dysfunction (ρ = .207), role dysfunction (ρ = .176), social dysfunction (ρ = .132), and poor quality of life (ρ = .178). All were statistically significant at p Conclusion The results show that the majority of cancer symptoms are associated with inflammation. The strength of the potential relationship between systemic inflammation and common cancer symptoms should be examined further within the context of an anti-inflammatory intervention trial.
TL;DR: A comprehensive literature review is performed to better understand and discuss issues related to therapeutic recommendations that are particular to patients 65 years and older with head and neck cancer.
Abstract: The incidence of head and neck cancer (HNC) in the elderly is increasing. The treatment of HNC often includes multimodality therapy that can be quite morbid. Older patients (herein, defined as ≥65 years) with HNC often have significant comorbidity and impaired functional status that may hinder their ability to receive and tolerate combined modality therapy. They have often been excluded from clinical trials that have defined standards of care. Therefore, tailoring cancer therapy for older patients with HNC can be quite challenging. In this paper, we performed a comprehensive literature review to better understand and discuss issues related to therapeutic recommendations that are particular to patients 65 years and older. Evidence suggests that older patients have similar survival outcomes compared with their younger peers; however, they may experience worse toxicity, especially with treatment intensification. Similarly, older patients may require more supportive care throughout the treatment process. Future studies incorporating geriatric tools for predictive and interventional purposes will potentially allow for improved patient selection and tolerance to intensive treatment.
TL;DR: Early treatment-related BP increases do not predict clinical benefit from bevacizumab based on PFS or OS outcomes and do not appear to have general prognostic importance for patients with advanced cancer.
Abstract: Background.
Hypertension is associated with antivascular endothelial growth factor treatment, but the clinical implications of hypertension are uncertain. To assess the prognostic and predictive value of bevacizumab-related hypertension, a comprehensive analysis of whether hypertension and efficacy outcomes are associated was conducted on seven company-sponsored placebo-controlled phase III studies of bevacizumab.
TL;DR: CTNNB1 mutations are indeed common in sporadic desmoid tumors, however, the study did not detect a statistically significant difference in recurrence risk according to either the CTNN B1 mutation status or the specific CTNNB2 codon mutation.
Abstract: Background.
Mutations in the gene-encoding β-catenin, CTNNB1, are highly prevalent in sporadic desmoid tumors and may predict the risk for recurrence. We sought to determine the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoid tumors and to determine whether CTNNB1 mutation status correlates with disease outcome.
TL;DR: The aim of this paper is to discuss the changes in diagnostic modalities and to focus on the recent alterations in the management of this rare disease, including targeted therapies as well as the more limited role of the endocrine surgeon.
Abstract: Primary thyroid lymphoma is rare, composing approximately 5% of all thyroid malignancies and less than 3% of all extranodal lymphomas. It typically presents as a rapidly enlarging goiter with associated compressive symptoms. Thyroid ultrasound and fine needle aspiration cytology, using flow cytometry and immunohistochemistry, remain the main modalities used to confirm the presence of lymphoma. The increasing use of an ultrasound-guided core biopsy to achieve an accurate diagnosis has further limited the role of surgery. An open surgical biopsy may still be required not only for definitive diagnosis but also to confirm the subtype of lymphoma. There are limited numbers of randomized or prospective trials to guide management, and controversy remains over optimal treatment. Treatment and prognosis of this disease can be dichotomized into two separate groups: pure mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL) or mixed subtypes. Early stage (stage IE) intrathyroidal MALT lymphomas typically have an indolent course and may be treated with single-modality surgery, radiotherapy, or a combination of both. DLBCLs are more aggressive, and survival outcomes are highest with multimodal therapy incorporating monoclonal antibodies, chemotherapy, and radiotherapy. The prognosis is generally excellent but can be varied because of the heterogeneous nature of thyroid lymphomas. The aim of this paper is to discuss the changes in diagnostic modalities and to focus on the recent alterations in the management of this rare disease, including targeted therapies as well as the more limited role of the endocrine surgeon.
TL;DR: The rising incidence and mortality of BC in young Latin American women is a call to action in the region and it is necessary to monitor the epidemiological and clinical data through reliable cancer registries and to consider the implementation of protocols for education of patients and health professionals.
Abstract: BACKGROUND Breast cancer (BC) is the leading cause of malignancy-related deaths among women aged ≤ 45 years. There are unexplored and uncertain issues for BC in this particular group in Latin America. The aim of this study is to evaluate BC incidence and mortality among young women and related clinicopathological and survivorship aspects in this region. MATERIALS AND METHODS Data were obtained from Globocan 2008 and the International Agency for Research on Cancer's Cancer Incidence in Five Continents series plus databases. We requested collaboration from the 12 different national cancer institutes in Latin America through SLACOM, the Latin American and Caribbean Society of Medical Oncology, and conducted a systematic literature review to obtain local data regarding the prevalence of BC among young women and their characteristics, outcomes, and survivorship-related issues. RESULTS BC incidence and mortality proportions for Latin American women aged <44 years were higher when compared with those of developed countries (20% vs. 12% and 14% vs. 7%, respectively). We found only a few Latin American series addressing this topic, and prevalence varied between 8% and 14%. Stage II and III disease, high histological grade, and triple-negative and HER2 BC were features frequently observed among young Latin American BC patients. CONCLUSION The rising incidence and mortality of BC in young Latin American women is a call to action in the region. It is necessary to monitor the epidemiological and clinical data through reliable cancer registries and to consider the implementation of protocols for education of patients and health professionals. This unmet, growing burden must be considered as a top priority of the national programs in the fight against BC, and models of specialized units should be implemented for this particular group of patients to provide better care for this emergent challenge.
TL;DR: Recognizing that QT prolongation is associated with TKI use facilitates identification of patients at high risk for this CV AE and increases awareness of the need for routine electrocardiograms and electrolyte monitoring for those receiving TKI treatment.
Abstract: Background Small-molecule tyrosine kinase inhibitors (TKIs) may provide an effective therapeutic option in patients with hematologic malignancies and solid tumors. However, cardiovascular (CV) events, including hypertension, heart failure, left ventricular systolic dysfunction, and QT prolongation, have emerged as potential adverse events (AEs) with TKI therapy. Purpose We review what is known about the mechanism of action of CV AEs associated with TKI use and discuss therapeutic interventions that may prevent and manage these events in clinical practice. Methods References for this review were identified through searches of PubMed and Medline databases, and only papers published in English were considered. Search terms included "cardiac," "cardiovascular," "cancer," and "kinase inhibitor." Related links in the databases were reviewed, along with relevant published guidelines. Results Although the link between rising blood pressure (BP) and CV AEs is observed but not proven, good clinical practice supports an aggressive policy on proper long-term BP management. There are insufficient data from randomized controlled clinical trials to show indisputably that aggressive or effective heart failure therapy in patients receiving TKIs will fundamentally change outcomes; however, clinical practice suggests that this is an effective long-term approach. Recognizing that QT prolongation is associated with TKI use facilitates identification of patients at high risk for this CV AE and increases awareness of the need for routine electrocardiograms and electrolyte monitoring for those receiving TKI treatment. Conclusion Regular monitoring, early recognition, and appropriate interventions for CV AEs can help more patients derive the benefit of long-term TKI therapy.
TL;DR: Investigation of AZD1480 when administered as monotherapy to patients with solid tumors revealed rapid absorption and elimination with minimal accumulation after repeated QD or b.i.d. dosing, and Pharmacodynamic analysis of circulating granulocytes demonstrated maximum phosphorylated STAT3 (pSTAT3) inhibition 1-2 hours after dose, coincident with Cmax, and greater pSTAT3 inhibition at higher doses.
Abstract: Background AZD1480 is a novel agent that inhibits Janus-associated kinases 1 and 2 (JAK1 and JAK2). The primary objective of this phase I study was to investigate the safety and tolerability of AZD1480 when administered as monotherapy to patients with solid tumors. Methods Thirty-eight patients with advanced malignancies were treated at doses of 10-70 mg once daily (QD) and 20-45 mg b.i.d. Results Pharmacokinetic (PK) analysis revealed rapid absorption and elimination with minimal accumulation after repeated QD or b.i.d. dosing. Exposure increased in a dose-dependent manner from 10-50 mg. Maximum plasma concentration (Cmax) was attained ∼1 hour after dose, and t1/2 was ∼5 hours. Pharmacodynamic analysis of circulating granulocytes demonstrated maximum phosphorylated STAT3 (pSTAT3) inhibition 1-2 hours after dose, coincident with Cmax, and greater pSTAT3 inhibition at higher doses. The average pSTAT3 inhibition in granulocytes at the highest dose tested, 70 mg QD, was 56% (standard deviation: ±21%) at steady-state drug levels. Dose-limiting toxicities (DLTs) consisted of pleiotropic neurologic adverse events (AEs), including dizziness, anxiety, ataxia, memory loss, hallucinations, and behavior changes. These AEs were generally reversible with dose reduction or treatment cessation. Conclusions Whether the DLTs were due to inhibition of JAK-1/2 or to off-target effects is unknown. The unusual DLTs and the lack of clinical activity led to discontinuation of development.
TL;DR: The disease is predominantly managed surgically and typically requires a total thyroidectomy and lymph node dissection and several emerging therapeutic targets have promise.
Abstract: Medullary thyroid cancer (MTC) typically accounts for 3%-4% of all thyroid cancers. Although the majority of MTCs are sporadic, 20% of cases are hereditary. Hereditary MTC can be found in multiple endocrine neoplasia 2A or 2B or as part of familial MTC based on a specific germline mutation in the RET proto-oncogene. This article discusses the current approaches available for the diagnosis, evaluation, and management of patients and their family members with suspected MTC. The disease is predominantly managed surgically and typically requires a total thyroidectomy and lymph node dissection. A review of recent guidelines on the extent and timing of surgical excision is discussed. There are not very many effective systemic treatment options for MTC, but several emerging therapeutic targets have promise.
TL;DR: The effectiveness of scalp cooling for hair preservation depends on dose and type of chemotherapy, with less favorable results at higher doses, and probably by the degree and duration of cooling.
Abstract: The success of scalp cooling in preventing or reducing chemotherapy-induced alopecia (CIA) is highly variable between patients and chemotherapy regimens. The outcome of hair preservation is often unpredictable and depends on various factors. Methods. We performed a structured search of literature published from 1970 to February 2012 for articles that reported on factors influencing the effectiveness of scalp cooling to prevent CIA in patients with cancer. Results. The literature search identified 192 reports, of which 32 studies were considered relevant. Randomized studies on scalp cooling are scarce and there is little information on the determinants of the result. The effectiveness of scalp cooling for hair preservation depends on dose and type of chemotherapy, with less favorable results at higher doses. Temperature seems to be an important determinant. Various studies suggest that a subcutaneous scalp temperature less than 22 °C is required for hair preservation. Conclusions. The effectiveness of scalp cooling for hair preservation varies by chemotherapy type and dose, and probably by the degree and duration of cooling.