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Journal: Journal of the National Comprehensive Cancer Network : JNCCN

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Mantle cell lymphoma (MCL) is a heterogenous disease with historically relative poor outcomes. However, new treatment strategies seem to be improving the prognosis for patients. Although no universally accepted standard of care exists, options for patients with newly diagnosed MCL include intensive and nonintensive strategies. Generally, intensive strategies produce more durable remissions and are selected for younger patients, whereas nonintensive strategies are most appropriate for older patients or patients with comorbidities. However, new options are closing the treatment gap between intensive and nonintensive strategies. Treatment options are also increasing for patients with relapsed/refractory MCL and include agents targeting the microenvironment and the B-cell receptor signaling pathway.

Concepts: Protein, Medical terms, Cell biology, Lymphoma, New York City, Mantle cell lymphoma

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Activating mutations in the HER2 tyrosine kinase have been identified in human breast cancers that lack HER2 gene amplification. These patients are not candidates for HER2-targeted drugs under current standards of care, but preclinical data strongly suggest that these patients will benefit from anti-HER2 drugs. This case report describes a young woman with metastatic breast cancer whose tumor was found to carry a HER2 L755S mutation, which is in the kinase domain of HER2. Treatment with the second-generation HER2/EGFR tyrosine kinase inhibitor neratinib resulted in partial response and dramatic improvement in the patient’s functional status. This partial response lasted 11 months, and when the patient’s cancer progressed, she was treated with neratinib plus capecitabine and her cancer again responded. This second response parallels the benefit seen with continuing trastuzumab in HER2-amplified breast cancer after disease progression. This case represents the first report, to our knowledge, of successful single-agent treatment of HER2-mutated breast cancer. Two clinical trials of neratinib for HER2-mutated metastatic breast cancer are currently enrolling patients. Further, data from The Cancer Genome Atlas project have identified HER2 mutations in a wide range of solid tumors, including bladder, colorectal, and non-small cell lung cancers, suggesting that clinical trials of neratinib or neratinib-based combinations for HER2-mutated solid tumors is warranted.

Concepts: Cancer, Breast cancer, Metastasis, Oncology, Lung cancer, Benign tumor, Tumor, Neoplasm

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In the current genomic era, increasing evidence demonstrates that approximately 2% of HER2-negative breast cancers, by current standard testings, harbor activating mutations of ERBB2. However, whether patients with HER2-negative breast cancer with activating mutations of ERBB2 also experience response to anti-HER2 therapies remains unclear. This case report describes a patient with HER2-nonamplified heavily pretreated breast cancer who experienced prolonged response to trastuzumab in combination with pertuzumab and fulvestrant. Further molecular analysis demonstrated that her tumors had an elevated HER2 dimerization that corresponded to ERBB2 S310F mutation. Located in the extracellular domain of the HER2 protein, this mutation was reported to promote noncovalent dimerization that results in the activation of the downstream signaling pathways. This case highlights the fact that HER2-targeted therapy may be valuable in patients harboring an ERBB2 S310F mutation.

Concepts: Cancer, Breast cancer, Trastuzumab, HER2/neu, Tamoxifen

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Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Recent statistics from the American Cancer Society indicate that the incidence of MM is increasing. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) included in this issue address management of patients with solitary plasmacytoma and newly diagnosed MM.

Concepts: Multiple myeloma, Cancer, Oncology, Bone marrow, American Cancer Society, Plasmacytoma

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Background: Guidelines recommend annual mammography after curative-intent treatment for breast cancer. The goal of this study was to assess contemporary patterns of breast imaging after breast cancer treatment. Methods: Administrative claims data were used to identify privately insured and Medicare Advantage beneficiaries with nonmetastatic breast cancer who had residual breast tissue (not bilateral mastectomy) after breast surgery between January 2005 and May 2015. We calculated the proportion of patients who had a mammogram, MRI, both, or neither during each of 5 subsequent 13-month periods. Multinomial logistic regression was used to assess associations between patient characteristics, healthcare use, and breast imaging in the first and fifth years after surgery. Results: A total of 27,212 patients were followed for a median of 2.9 years (interquartile range, 1.8-4.6) after definitive breast cancer surgery. In year 1, 78% were screened using mammography alone, 1% using MRI alone, and 8% using both tests; 13% did not undergo either. By year 5, the proportion of the remaining cohort (n=4,790) who had no breast imaging was 19%. Older age was associated with an increased likelihood of mammography and a decreased likelihood of MRI during the first and fifth years. Black race, mastectomy, chemotherapy, and no MRI at baseline were all associated with a decreased likelihood of both types of imaging. Conclusions: Even in an insured cohort, a substantial proportion of breast cancer survivors do not undergo annual surveillance breast imaging, particularly as time passes. Understanding factors associated with imaging in cancer survivors may help improve adherence to survivorship care guidelines.

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The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.

Concepts: Cancer, Digestive system, Liver, Hepatology, Bile, Bile duct, Gallbladder, The Panel

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Background: Physical activity (PA) during and after cancer treatment can help with symptom management and reduce the risk of cancer recurrence. However, it is unclear what constitutes an optimal exercise program. In addition, provider and patient barriers exist to the recommendation and adoption of exercise as part of a cancer treatment plan. The goal of this study was to determine how providers and patients feel about exercise during cancer treatment and explore what the barriers to implementing such a program might be. Patients and Methods: Focus groups and interviews were held with patients with malignancy, both metastatic and nonmetastatic, and oncology providers. In total, 20 patients participated in either a focus group or an individual interview and 9 providers contributed to the focus group. An equal number of patients (n=10) were interviewed as attended a focus group. Audiotaped sessions were transcribed verbatim. Theme identification was independently coded by 4 coders and synthesized as a group. Results: Neither patient group recalled PA instruction from oncology providers during their cancer treatment. Most participants (95%) felt exercise is important during cancer treatment, citing overall well-being benefits versus improved disease outcome. Most patients (80%) preferred a home-based exercise program provided by the oncologist. Fatigue was the most cited barrier to regular exercise during treatment (50%). All providers acknowledged benefits of PA to patients, but not universally for all. More than half of providers (55%) preferred a referral system for exercise programs. Clinic visit time constraints and a perceived lack of expertise in the area of PA were common barriers to making exercise recommendations a routine part of the treatment plan. Conclusions: Patients with cancer and oncologists recognize the benefits of PA during treatment. Disagreement exists between to whom, how, and where exercise plans should be disseminated and implemented.

Concepts: Cancer, Metastasis, Oncology, Focus group, Chemotherapy, Exercise, Tumor, Malignancy

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Background: Hospitals' use of observation status for patients with cancer presenting to the emergency department (ED) is not well understood. This model of care delivery may be a viable alternative to inpatient admission for patients with cancer presenting with certain conditions. Our objective was to assess the use of observation status among Medicare beneficiaries with and without cancer. Methods: Population-based SEER-Medicare data were used to assess differences in the use of observation status between Medicare beneficiaries aged ≥66 years with and without cancer using a matched analysis (n=151,183 per cohort). We assessed the ratio of observation unit use to inpatient admission, between cancer and noncancer cohorts, and for patients diagnosed with breast, colon, lung, and prostate cancers. Poisson regression models were used to calculate observation rate estimates and 95% CIs while adjusting for selected patient characteristics. Results: When considering the volume of hospitalizations, observation status is used less frequently among beneficiaries with cancer than those without (43 vs 69 observation status visits per 1,000 inpatient admissions, respectively). The estimated observation rate per 1,000 inpatient admissions was higher for beneficiaries aged <75 years versus those aged ≥75 years, those with a Charlson comorbidity index of 0 vs 1 or ≥2, and those without a prior hospitalization versus those with ≥1 prior hospitalizations. Patients with breast and prostate cancers had higher adjusted and unadjusted observation rates per 1,000 inpatient admissions compared with those with colon and lung cancers. Conclusions: Observation status is used proportionately less for beneficiaries with cancer than those without. There may be opportunities to develop standards for ED staff to manage certain conditions for patients with cancer in observation status, and to reserve hospital resources for those who need it most.

Concepts: Regression analysis, Cancer, Breast cancer, Metastasis, Lung cancer, Hospital, Prostate cancer, Comorbidity

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Background: For trials to validly evaluate new treatments, comparison against the best existing alternative treatment is essential. We reviewed the care provided to women in control arms of breast cancer clinical trials to estimate the proportion consistent with the standard of care as defined in clinical guidelines. Methods: We analyzed phase III randomized controlled breast cancer trials comparing drug treatments with “standard care,” enrolling between 2004 and 2014, and registered on ClinicalTrials.gov Our primary outcome was the proportion of trials in which treatment in the control arm was consistent with concurrent NCCN Guidelines. A secondary analysis assessed trials recruiting outside the United States that provided control group therapy not consistent with NCCN Guidelines, comparing them with the German Gynecological Oncology Group (AGO) guidelines. We assessed associations between the primary outcome and a priori selected trial characteristics. Results: This study included 210 trials that recruited 229,182 women worldwide; 29% of trials (60/210) did not provide control group treatment that was consistent with NCCN Guidelines. For trials not recruiting in the United States, results were similar; in 21% of trials, control arm treatment was inconsistent with both AGO and NCCN Guidelines. Factors significantly associated with offering control arm treatment that were inconsistent with guidelines were time period (later trials were less likely to be consistent), breast cancer stage and type (trials in early-stage breast cancer and estrogen receptor-negative disease were less likely consistent), and recruitment in ≥4 countries and recruitment outside the United States. Conclusions: To ensure that clinical trials achieve their goal of obtaining the best information to guide patient treatment, the question of how investigators chose and describe “standard care” for control arm participants warrants further investigation.

Concepts: Clinical trial, Cancer, Breast cancer, Oncology, Cancer staging, United States, Estrogen, ClinicalTrials.gov

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Background: Squamous cell carcinoma of the anus (SCCA) is one of the few cancers with an increasing incidence in the United States. We aimed to characterize race- and sex-based disparities in receipt of therapy and overall survival (OS) of SCCA using the SEER database. Methods: Cases of locoregional SCCA (T2-T4 any N M0) diagnosed between 2000 and 2012 in the SEER database were included. Demographics, tumor characteristics, type of therapy, and outcomes were extracted. Univariable and multivariable Cox proportional hazard models were constructed to test factors associated with OS. Data were reported as hazard ratios (HRs) and 95% CIs. Results: A total of 7,882 cases of locoregional SCCA were identified, with a median age of 58 years, 61.2% of whom were women, and 86.3% were white. Most patients (82.3%) received radiation therapy (RT), with the lowest rate in black men (76.7%) and the highest in white women (86.1%). The median OS was 135 months; OS was lower in elderly patients (age ≥65 years; 68 months), men (108 months), blacks (109 months), and those who did not receive RT (121 months). In multivariable analysis, age (HR, 1.19; 95% CI, 1.17-1.21 per 5 years increase), sex (HR, 1.59; 95% CI, 1.47-1.73, men vs women), race (HR, 1.51; 95% CI, 1.34-1.71, black vs white), and RT (HR, 0.90; 95% CI, 0.82-0.99) were independently associated with OS (P<.05). Conclusions: Significant race- and sex-based disparities exist in survival of patients with locoregional SCCA. Further investigation into the causes of these disparities and methods for elimination are warranted.

Concepts: Cancer, Proportional hazards models, Black people, Squamous cell carcinoma, Squamous epithelium, Race, White American, White people