bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor–Positive, Node-Positive Early Breast Cancer: Final Results of the Randomized Phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial
Authors: Smith Ian , Yardley Denise , Burris Howard A. , De Boer Richard , Amadori Dino , McIntyre Kristi , Ejlertsen Bent , Gnant Michael , Jonat Walter , Pritchard Kathleen I. , Dowsett Mitch , Hart Lowell , Poggio Susan , Comarella Lisa , Salomon Herve , Wamil Barbara , O’Shaughnessy Joyce 
Published: February 2017

Purpose The Letrozole (Femara) Versus Anastrozole Clinical Evaluation (FACE) study compared the efficacy and safety of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor (HR) –positive and node-positive early breast cancer (eBC). Methods Postmenopausal women with HR-positive and node-positive eBC were randomly assigned to receive adjuvant therapy with either letrozole (2.5 mg) or anastrozole (1 mg) once per day for 5 years or until recurrence of disease. Patients were stratified on the basis of the number of lymph nodes and human epidermal growth factor receptor 2 status. The primary end point was 5-year disease-free survival (DFS), and the key secondary end points were overall survival and safety. Results A total of 4,136 patients were randomly assigned to receive either letrozole (n = 2,061) or anastrozole (n = 2,075). The final analysis was done at 709 DFS events (letrozole, 341 [16.5%]; anastrozole, 368 [17.7%]). The 5-year estimated DFS rate was 84.9% for letrozole versus 82.9% for anastrozole arm (hazard ratio, 0.93; 95% CI, 0.80 to 1.07; P = .3150). Exploratory analysis showed similar DFS with letrozole and anastrozole in all evaluated subgroups. The 5-year estimated overall survival rate was 89.9% for letrozole versus 89.2% for anastrozole arm (hazard ratio, 0.98; 95% CI, 0.82 to 1.17; P = .7916). Most common grade 3 to 4 adverse events (> 5% of patients) reported for letrozole versus anastrozole were arthralgia (3.9% v 3.3%, and 48.2% v 47.9% for all adverse events), hypertension (1.2% v 1.0%), hot flushes (0.8% v 0.4%), myalgia (0.8% v 0.7%), dyspnea (0.8% v 0.5%), and depression (0.8% v 0.6%). Conclusion Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR-positive, node-positive eBC.
Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance)
Authors: Ellis Matthew J. , Suman Vera J. , Hoog Jeremy , Goncalves Rodrigo , Sanati Souzan , Creighton Chad J. , DeSchryver Katherine , Crouch Erika , Brink Amy , Watson Mark , Luo Jingqin , Tao Yu , Barnes Michael , Dowsett Mitchell , Budd G. Thomas , Winer Eric , Silverman Paula , Esserman Laura , Carey Lisa , Ma Cynthia X. , Unzeitig Gary , Pluard Timothy , Whitworth Pat , Babiera Gildy , Guenther J. Michael , Dayao Zoneddy , Ota David , Leitch Marilyn , Olson John A. , Allred D. Craig , Hunt Kelly 
Published: February 2017

Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) –positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratified Cox modeling was used to assess whether time to recurrence differed by PEPI = 0 score (T1 or T2, N0, Ki67 < 2.7%, ER Allred > 2) versus PEPI > 0 disease. Results Only two of the 35 patients in ACOSOG Z1031B who were switched to neoadjuvant chemotherapy experienced a pCR (5.7%; 95% CI, 0.7% to 19.1%). After 5.5 years of median follow-up, four (3.7%) of the 109 patients with a PEPI = 0 score relapsed versus 49 (14.4%) of 341 of patients with PEPI > 0 (recurrence hazard ratio [PEPI = 0 v PEPI > 0], 0.27; P = .014; 95% CI, 0.092 to 0.764). Conclusion Chemotherapy efficacy was lower than expected in ER-positive tumors exhibiting AI-resistant proliferation. The optimal therapy for these patients should be further investigated. For patients with PEPI = 0 disease, the relapse risk over 5 years was only 3.6% without chemotherapy, supporting the study of adjuvant endocrine monotherapy in this group. These Ki67 and PEPI triage approaches are being definitively studied in the ALTERNATE trial (Alternate Approaches for Clinical Stage II or III Estrogen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women: A Phase III Study; clinical trial information: NCT01953588).
Management of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis
Authors: Magnuson William J. , Lester-Coll Nataniel H. , Wu Abraham J. , Yang T. Jonathan , Lockney Natalie A. , Gerber Naamit K. , Beal Kathryn , Amini Arya , Patil Tejas , Kavanagh Brian D. , Camidge D. Ross , Braunstein Steven E. , Boreta Lauren C. , Balasubramanian Suresh K. , Ahluwalia Manmeet S. , Rana Niteshkumar G. , Attia Albert , Gettinger Scott N. , Contessa Joseph N. , Yu James B. , Chiang Veronica L. 
Published: February 2017

Purpose Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non–small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI. Materials and Methods A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases. Results The median OS for the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respectively ( P < .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis ( P = .001). Conclusion This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed.
Concurrent Chemotherapy and Radiation Therapy for Inoperable Locally Advanced Non–Small-Cell Lung Cancer
Authors: Rosenzweig Kenneth E. , Gomez Jorge E. 
Published: February 2017

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 72-year-old man with a 40-pack-year tobacco history developed a cough and decreased exercise tolerance. A chest x-ray demonstrated a right-upper-lobe opacity. Chest computed tomography (CT) scan revealed a 2.5-cm mass in the right upper lobe with multiple mediastinal lymph node disease ( Fig 1 ). A positron emission tomography (PET) scan confirmed the lung lesion and the mediastinal lymphadenopathy without distant metastases. Brain magnetic resonance imaging results were negative. The biopsy specimen revealed adenocarcinoma with no actionable mutations present. Cervical mediastinoscopy was positive for carcinoma in level 2, 3, 4R, and 7 lymph nodes; level 4L was negative. The patient’s stage was T1bN2M0, stage IIIA. His medical history was significant for hyperlipidemia and hypothyroidism. He had smoked one pack a day for 40 years and had quit 15 years earlier. Physical examination was unrevealing, and the patient had an Eastern Cooperative Oncology Group performance status of 0. Because of the extent of lung cancer in the mediastinum, the patient’s cancer was deemed inoperable, and he was referred for consideration of concurrent chemotherapy and radiation.
BTKC481S-Mediated Resistance to Ibrutinib in Chronic Lymphocytic Leukemia
Authors: Woyach Jennifer A. , Ruppert Amy S. , Guinn Daphne , Lehman Amy , Blachly James S. , Lozanski Arletta , Heerema Nyla A. , Zhao Weiqiang , Coleman Joshua , Jones Daniel , Abruzzo Lynne , Gordon Amber , Mantel Rose , Smith Lisa L. , McWhorter Samantha , Davis Melanie , Doong Tzyy-Jye , Ny Fan , Lucas Margaret , Chase Weihong , Jones Jeffrey A. , Flynn Joseph M. , Maddocks Kami , Rogers Kerry , Jaglowski Samantha , Andritsos Leslie A. , Awan Farrukh T. , Blum Kristie A. , Grever Michael R. , Lozanski Gerard , Johnson Amy J. , Byrd John C. 
Published: February 2017

Purpose Therapeutic targeting of Bruton tyrosine kinase (BTK) with ibrutinib in chronic lymphocytic leukemia has led to a paradigm shift in therapy, and relapse has been uncommon with current follow-up. Acquired mutations in BTK and PLCG2 can cause relapse, but data regarding the prevalence and natural history of these mutations are limited. Patients and Methods Patients accrued to four sequential studies of ibrutinib were included in these analyses. Deep sequencing for BTK and PLCG2 was performed retrospectively on patients who experienced relapse and prospectively on a screening population. Results With a median follow-up time of 3.4 years, the estimated cumulative incidence of progression at 4 years is 19% (95% CI, 14% to 24%). Baseline karyotypic complexity, presence of del(17)(p13.1), and age less than 65 years were risk factors for progression. Among patients who experienced relapse, acquired mutations of BTK or PLCG2 were found in 85% (95% CI, 71% to 94%), and these mutations were detected an estimated median of 9.3 months (95% CI, 7.6 to 11.7 months) before relapse. Of a group of 112 patients examined prospectively, eight patients have experienced relapse, and all of these patients had acquired resistance mutations before relapse. A resistance mutation was detected in an additional eight patients who have not yet met criteria for clinical relapse. Conclusion Relapse of chronic lymphocytic leukemia after ibrutinib is an issue of increasing clinical significance. We show that mutations in BTK and PLCG2 appear early and have the potential to be used as a biomarker for future relapse, suggesting an opportunity for intervention.
Survey of Implementation of Antiemetic Prescription Standards in Indian Oncology Practices and Its Adherence to the American Society of Clinical Oncology Antiemetic Clinical Guideline
Authors: Patil Vijay , Noronha Vanita , Joshi Amit , Parikh Purvish , Bhattacharjee Atanu , Chakraborty Santam , Jandyal Sunny , Muddu Vamshi , Ramaswamy Anant , Babu K. Govinda , Lokeshwar Nilesh , Hingmire Sachin , Ghadyalpatil Nikhil , Banavali Shripad , Prabhash Kumar 
Published: February 2017

Purpose Adherence to international antiemetic prophylaxis guidelines like those of ASCO can result in better control of chemotherapy-induced nausea and vomiting; however, the extent of implementation of such guidelines in India is unknown. Therefore, this survey was planned. Methods This study was an anonymized cross-sectional survey approved by the ethics committee. Survey items were generated from the clinical questions given in the ASCO guidelines. The survey was disseminated through personal contacts at an oncology conference and via e-mail to various community oncology centers across India. The B1, B2, and B3 domains included questions regarding the optimal antiemetic prophylaxis for high, moderate, and low-minimal emetogenic regimens. Results Sixty-six (62.9%) of 105 responded and 65 centers (98.5%) were aware of the published guidelines. The partial, full, and no implementation scores were 92.5%, 4.5%, and 3.0%, respectively. Full implementation was better for the low-minimal emetogenic regimens (34.8%) than the highly emetogenic regimens (6.1%). The three most frequent reasons for hampered implementation of ASCO guidelines in routine chemotherapy practice cited by centers were a lack of sensitization (26 centers; 39.4%), lack of national guidelines (12 centers; 18.2%), and lack of administrative support (10 centers; 15.2%). Conclusion Awareness regarding ASCO antiemetic guidelines is satisfactory in Indian oncology practices; however, there is a need for sensitization of oncologists toward complete implementation of these guidelines in their clinical practice.
Health-Seeking Behavior and Barriers to Care in Patients With Rectal Bleeding in Nigeria
Authors: Alatise Olusegun I. , Fischer Sara E. , Ayandipo Omobolaji O. , Omisore Akinlolu G. , Olatoke Samuel A. , Kingham T. Peter 
Published: February 2017

PurposeColorectal cancer (CRC) incidence rates are steadily increasing in Nigeria. Organized screening is still largely unused because of financial and logistical barriers; most CRCs are detected by symptoms. One symptom of CRC is rectal bleeding. This study sought to determine health-seeking behavior and barriers to care in patients with rectal bleeding in Nigeria. This study also surveyed physicians to determine major breakdowns in access to care.MethodsThe recruitment process for this study involved patients referred for colonoscopy because of rectal bleeding as well as response to a media advertisement for a free colonoscopy. Physicians were recruited at the African Research Group for Oncology meeting. Patient responses were scored on the basis of knowledge of rectal bleeding. The physician questionnaire was supporting information and mainly descriptive in nature.ResultsA total of 82 patients and 45 physicians participated in this study. Less than 40% of patients knew that rectal bleeding could be caused by cancer. Major barriers to care were resolution of the symptom (42%), no consideration of the bleeding as problematic (40%), and financial constraint (22%). Education was strongly correlated with knowledge of rectal bleeding and health-seeking behavior. Although physicians regularly saw patients with rectal bleeding, most of them provided a differential diagnosis of hemorrhoids and few referred patients for colonoscopy.ConclusionGeneral awareness about the signs of colorectal cancer is lacking. This demonstrates the strong need for patient education programs about this issue. Physicians should also receive additional training on differentiation of a potential cancer diagnosis from something more benign, such as hemorrhoids.
Outcomes in Lung Cancer: 9-Year Experience From a Tertiary Cancer Center in India
Authors: Murali Aditya Navile , Radhakrishnan Venkatraman , Ganesan Trivadi S. , Rajendranath Rejiv , Ganesan Prasanth , Selvaluxmy Ganesarajah , Swaminathan Rajaraman , Sundersingh Shirley , Krishnamurthy Arvind , Sagar Tenali Gnana 
Published: February 2017

Purpose Lung cancer is the most common cause of cancer mortality in the world. There are limited studies on survival outcomes of lung cancer in developing countries such as India. This study analyzed the outcomes of patients with lung cancer who underwent treatment at Cancer Institute (WIA), Chennai, India, between 2006 and 2015 to determine survival outcomes and identify prognostic factors. Patients and Methods In all, 678 patients with lung cancer underwent treatment. Median age was 58 years, and 91% of patients had non–small-cell lung cancer (NSCLC). Testing for epidermal growth factor receptor mutation was performed in 132 of 347 patients and 61 (46%) were positive. Results Median progression-free survival was 6.9 months and overall survival (OS) was 7.6 months for patients with NSCLC. Median progression-free survival was 6 months and OS was 7.2 months for patients with small-cell lung cancer. On multivariable analysis, the factors found to be significantly associated with inferior OS in NSCLC included nonadenocarcinoma histology, performance status more than 2, and stage. In small-cell lung cancer, younger age and earlier stage at presentation showed significantly better survival. Conclusion Our study highlights the challenges faced in treating lung cancer in India. Although median survival in advanced-stage lung cancer is still poor, strategies such as personalized medicine and use of second-line and maintenance chemotherapy may significantly improve the survival in patients with advanced-stage lung cancer in developing countries.
Differences in Health Care Use and Costs Among Patients With Cancer Receiving Intravenous Chemotherapy in Physician Offices Versus in Hospital Outpatient Settings
Authors: Fisher Maxine D. , Punekar Rajeshwari , Yim Yeun Mi , Small Arthur , Singer Joseph R. , Schukman Jay , McAneny Barbara L. , Luthra Rakesh , Malin Jennifer 
Published: February 2017

Purpose: The current shift in site of care from community oncology practices to the hospital outpatient department to deliver oncology services may have significant implications for the economic and clinical outcomes of cancer care. Therefore, this study compares health care use and costs among patients with cancer receiving intravenous (IV) chemotherapy in physician offices (PO) versus in hospital outpatient settings (HOP). Methods: This retrospective study, which was based on medical and pharmacy claims data, included patients (age, 18 to 64 years) initiating IV chemotherapy/biologic treatment between January 1, 2006, and August 31, 2012, who were diagnosed with early or metastatic breast cancer, metastatic lung cancer, metastatic colorectal cancer, or non-Hodgkin lymphoma or chronic lymphocytic leukemia. Patients were assigned to PO or HOP groups on the basis of where they received > 95% of their IV cancer therapy. Results: The study sample included 18,740 patients (12,899 PO; 5,841 HOP) who had a mean age of 51.6 years and a Deyo-Charlson Comorbidity Index score of 5.37. Overall office visits (21.8 ± 13.8 PO v 21.2 ± 12.9, P < .005) and outpatient services (50.8 ± 35.5 PO v 48.5 ± 33.6, P < .001) were higher in the PO group than in the HOP group. Cancer-related inpatient hospitalizations (0.6 ± 1.2 PO v 0.7 ± 1.4 HOP, P = .002) were lower in the PO group than in the HOP group. Although quality-of-care metrics were similar between the HOP and PO groups, follow-up all-cause costs ($82,773 PO v $122,473 HOP) and cancer-related health care costs ($69,037 PO v $108,177 HOP) were higher in the HOP group than in the PO group. Conclusion: Despite similar resource use, all-cause and cancer-related health care costs in HOP were significantly higher compared with those in PO settings.
Anxiety, Culture, and Expectations: Oncologist-Perceived Factors Associated With Use of Nonrecommended Serum Tumor Marker Tests for Surveillance of Early-Stage Breast Cancer
Authors: Hahn Erin E. , Munoz-Plaza Corrine , Wang Jianjin , Garcia Delgadillo Jazmine , Schottinger Joanne E. , Mittman Brian S. , Gould Michael K. 
Published: February 2017

Purpose: Breast cancer offers several opportunities for reducing use of ineffective practices based on American Society of Clinical Oncology guidelines. We assessed oncologist-perceived factors associated with use of one such practice—serum tumor markers for post-treatment breast cancer surveillance—focusing on medical oncologists with high, medium, or low test use. Methods: Using a mixed-methods design, we identified patients who had been treated for early-stage breast cancer diagnosed between January 1, 2009, and December 31, 2012, within Kaiser Permanente Southern California and calculated the number of tests ordered from January 1, 2010, to December 31, 2014. We identified oncologists with high, medium, or low use and subsequently performed semistructured interviews. We used patient satisfaction data to assess association between pattern of use and satisfaction score. Results: We identified 7,363 patients, with 40,114 tests ordered. High-use oncologists were defined as those ordering at least one test annually for 35% of patients or more, low-use oncologists as those ordering at least one test for 5% of patients or less; 42% of oncologists were high, 27% low, and 31% medium users. We interviewed 17 oncologists: six high, eight low, and three medium users. Factors associated with high use included: perceived patient anxiety, oncologist anxiety, belief that there was nothing else to offer, concern about satisfaction, patient competition, peer use, and system barriers. Factors associated with low use included: beliefs about consequences (eg, causes harms) and medical center culture (eg, collective decision to follow guidelines). We found no association between satisfaction score and pattern of use. Conclusion: Barriers to deimplementation are numerous and complex. Traditional strategies of practice change alone are unlikely to be effective. Multifaceted, multilevel strategies deployed to address patient-, clinician-, and system-related barriers may be required.