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Zachary Veitch, Omar F. Khan, Derek Tilley, Domek Ribnikar, Xanthoula Kostaras, Karen King, Patricia Tang and Sasha Lupichuk

Background: Comparative real-world outcomes for patients with HER2-positive (HER2+) breast cancer receiving adjuvant trastuzumab outside of clinical trials are lacking. This study sought to retrospectively characterize outcomes for patients with node-negative and node-positive breast cancer receiving adjuvant trastuzumab in combination with docetaxel/cyclophosphamide (DCH), docetaxel/carboplatin/trastuzumab (TCH), or fluorouracil/epirubicin/cyclophosphamide followed by docetaxel/trastuzumab (FEC-DH) chemotherapy in Alberta, Canada, from 2007 through 2014. Methods: Disease-free survival and overall survival (OS) analyses for node-negative cohorts receiving DCH (n=111) or TCH (n=371) and node-positive cohorts receiving FEC-DH (n=146) or TCH (n=315) were compared using chi-square, Kaplan-Meier, or Cox multivariable analysis where appropriate. Results: Median follow-up was similar in node-negative (63.9 months) and node-positive (69.0 months) cohorts. The 5-year OS rates in patients with node-negative disease receiving DCH or TCH were similar (95.2% vs 96.9%; P=.268), whereas 5-year OS rates were higher but nonsignificant for patients with node-positive disease treated with FEC-DH compared with TCH (95.2% vs 91.4%; P=.160). Subgroup analysis of node-positive cohorts showed significantly improved OS with FEC-DH versus TCH in patients with estrogen receptor (ER)/progesterone receptor (PR)–positive breast cancer (98.3% vs 91.6%, respectively; P=.014). Conversely, patients with ER/PR-negative disease showed a nonsignificant trend toward higher OS rates with TCH versus FEC-DH (91.6% vs 83.3%, respectively; P=.298). Given the retrospective design, we were unable to capture all potential covariates that may have impacted treatment assignment and/or outcomes. Furthermore, cardiac toxicity data were unavailable. Conclusions: Survival rates of patients with HER2+ breast cancer in our study are comparable to those seen in clinical trials. Our findings support chemotherapy de-escalation in patients with node-negative disease and validate the efficacy of FEC-DH in those with node-positive disease.

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Kathryn P. Pennington, Renata R. Urban and Heidi J. Gray

Minimally invasive surgery (MIS) was previously considered an acceptable alternative to open radical hysterectomy in the management of early-stage cervical cancer (ESCC), but adequately powered, high-quality prospective trials evaluating survival outcomes were lacking. Recently, a large randomized phase III trial, the Laparoscopic Approach to Cervical Cancer (LACC) trial, showed that MIS for ESCC is associated with a higher risk of recurrence and death compared with open surgery. We review the LACC trial findings in depth, as well as a recent National Cancer Database analysis using propensity score weighting that supports the LACC trial findings. Additional studies are needed to better understand the mechanisms explaining the worse survival associated with MIS for ESCC. This review discusses considerations for integrating the findings of the LACC trial into clinical practice. Based on the high-quality evidence now available, open radical hysterectomy should be offered as standard of care for stage IA2–IB1 cervical cancer and patients should be guided appropriately to make informed shared decision-making if they still desire MIS.

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Brandon A. Dyer, Dmitriy Zamarin, Ramez N. Eskandar and Jyoti M. Mayadev

Despite combined therapeutic approaches, there is an unmet clinical need to identify effective strategies for improved patient outcomes in treating locally advanced and metastatic cervical cancer (CC). Immunotherapy is emerging as a novel therapeutic approach in this disease for which the causative agent, human papillomavirus (HPV), has dynamic, complex immunomodulatory effects. This review explores the biologic rational of immuno-oncology in the treatment of CC and discusses the initial clinical efficacy, ongoing clinical trials, and rationale for combined multimodal treatment approaches for locally advanced and recurrent/metastatic CC. The utility of immune checkpoint inhibitors is explored, including anti–cytotoxic T-lymphocyte antigen-4 (CTLA-4), PD-1, and PD-L1. Preliminary data supporting the combination of radiotherapy and immunotherapy and areas of active drug development for CC are also reviewed.

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Kerry Schaffer, Narmadha Panneerselvam, Kah Poh Loh, Rachel Herrmann, Ian R. Kleckner, Richard Francis Dunne, Po-Ju Lin, Charles E. Heckler, Nicholas Gerbino, Lauren B. Bruckner, Eugene Storozynsky, Bonnie Ky, Andrea Baran, Supriya Gupta Mohile, Karen Michelle Mustian and Chunkit Fung

Background: Exercise can ameliorate cancer- and treatment-related toxicities, but poor adherence to exercise regimens is a barrier. Exercise interventions using digital activity trackers (E-DATs) may improve exercise adherence, but data are limited for patients with cancer. We conducted a systematic review examining the feasibility of E-DATs in cancer survivors and effects on activity level, body composition, objective fitness outcomes, health-related quality of life (HRQoL), self-reported symptoms, and biomarkers. Methods: We identified randomized controlled trials (RCTs) of E-DATs in adult cancer survivors published in English between January 1, 2008, and July 27, 2017. Two authors independently reviewed article titles (n=160), removed duplicates (n=50), and reviewed the remaining 110 articles for eligibility. Results: A total of 12 RCTs met eligibility criteria, including 1,450 patients (mean age, 50–70 years) with the following cancers: breast (n=5), colon or breast (n=2), prostate (n=1), acute leukemia (n=1), or others (n=3). Duration of E-DATs ranged from 4 to 24 weeks, and the follow-up period ranged from 4 to 52 weeks, with retention rates of 54% to 95%. The technology component of E-DATs included pedometers (n=8); pedometers with smartphone application (n=1), Wii Fit (n=1), heart rate monitor (n=1); and a wireless sensor with accelerometer, gyroscope, and magnetometer (n=1). Adherence by at least one measure to E-DATs was >70% in 8 of 8 RCTs. Compared with controls, E-DATs significantly improved patients' step count in 3 of 5 RCTs, activity level in 6 of 9 RCTs, and HRQoL in 7 of 9 RCTs (all P≤.05), with no significant changes in biomarkers (eg, interleukin 6, tumor necrosis factor α, C-reactive protein, c-peptide, lipid panel) in 3 RCTs. Duration of E-DAT was not significantly correlated with adherence or study retention. Conclusions: This systematic review shows that E-DATs are feasible to implement in cancer survivors. Future research should examine the optimal type, dose, and schedule of E-DATs for cancer survivors.

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Siyang Leng, Yizhen Chen, Wei-Yann Tsai, Divaya Bhutani, Grace C. Hillyer, Emerson Lim, Melissa K. Accordino, Jason D. Wright, Dawn L. Hershman, Suzanne Lentzsch and Alfred I. Neugut

Background: Bisphosphonates reduce skeletal-related events (SREs) in patients with multiple myeloma (MM) and, in some studies, improved survival. Since 2011, bisphosphonate use has been recommended by NCCN for all patients with newly diagnosed MM receiving antineoplastic therapy independent of the presence of bone disease. This study investigated their use after these guidelines were established. Methods: We identified patients aged ≥65 years in the SEER-Medicare database with newly diagnosed MM between January 1, 2012, and December 31, 2013, who received antineoplastic therapy, had ≥6 months of follow-up, and did not receive prior bisphosphonates. Presence of SREs at diagnosis was identified, including pathologic fracture, spinal cord compression, radiation to bone, or surgery to bone. Use of bisphosphonates was defined as having ≥1 claim for an intravenous or oral bisphosphonate within 6 months after the start of antineoplastic therapy. We used multivariable modeling to compare users with nonusers, controlling for demographic and clinical covariates. We compared overall survival between users and nonusers using proportional hazards analysis. Results: Of 1,309 patients identified, 720 (55%) used a bisphosphonate. Factors associated with use included SRE at diagnosis (adjusted odds ratio [AOR], 2.60; 95% CI, 1.98–3.40), hypercalcemia (AOR, 1.74; 95% CI, 1.26–2.41), and use of proteasome inhibitor + immunomodulatory imide therapy (AOR, 1.70; 95% CI, 1.21–2.39). Chronic kidney disease (AOR, 0.48; 95% CI, 0.35–0.66) was associated with decreased use. Bisphosphonate use was associated with reduced mortality (hazard ratio, 0.70; 95% CI, 0.56–0.88). Conclusions: Although bisphosphonate use is recommended for all patients with newly diagnosed MM receiving antineoplastic therapy, 45% of patients in the United States did not receive this guideline-recommended care.

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Chadi Nabhan, Eli G. Phillips Jr and Bruce A. Feinberg

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Ali A. Mokdad, Rebecca M. Minter, Adam C. Yopp, Matthew R. Porembka, Sam C. Wang, Hong Zhu, Mathew M. Augustine, John C. Mansour, Michael A. Choti and Patricio M. Polanco

Background: Preoperative therapy is being increasingly used in the treatment of resectable pancreatic cancer. Because there are only limited data on the optimal preoperative regimen, we compared overall survival (OS) between preoperative chemotherapy (CT) and preoperative chemoradiotherapy (CRT) in resectable pancreatic adenocarcinoma. Patients and Methods: Patients receiving preoperative therapy and resection for clinical T1–3N0–1M0 adenocarcinoma of the pancreas were identified in the National Cancer Database for 2006 through 2012. We constructed inverse probability of treatment weights to balance baseline group differences, and compared OS between CT and CRT, as well as pathologic and postoperative findings. Results: We identified 1,326 patients (CT: 616; CRT: 710). Differences in OS were not significant between CRT and CT (median survival, 25 vs 26 months; P=.10; weight-adjusted hazard ratio, 0.89; 95% CI, 0.77–1.02). Compared with patients in the CT group, those in the CRT group had lower pathologic T stage (ypT0/T1/T2: 36% vs 21%; P<.01), less lymph node involvement (ypN1: 35% vs 59%; P<.01), and fewer positive resection margins (14% vs 21%; P=.01), but had more postoperative unplanned readmissions (9% vs 6%; P=.01) and increased 90-day mortality (7% vs 4%; P=.03). Those in the CRT group were also less likely to receive postoperative therapy (26% vs 51%; P<.01). Conclusions: Preoperative CT and CRT have similar OS, but CRT is associated with more favorable pathologic features at the cost of higher postoperative morbidity and mortality. Additional trials investigating preoperative therapy are needed for patients with resectable pancreatic cancer.

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Kshama Jaiswal, Madelyne Hull, Anna L. Furniss, Reina Doyle, Natalia Gayou and Elizabeth Bayliss

Background: Timely detection and treatment of breast cancer is important in optimizing survival and minimizing recurrence. Given disparities in breast cancer outcomes based on socioeconomic status, we examined time to diagnosis and treatment in a safety-net hospital. Methods: We conducted a retrospective review of all patients with breast cancer diagnosed between July 1, 2010, and June 30, 2012 (N=120). We limited our analytic sample to patients with nonrecurrent, primary stage 0–III breast cancer (N=105) and determined intervals from presentation to diagnosis, diagnosis to first treatment, last surgery to chemotherapy initiation, and last surgery to start of radiation therapy (RT). Using logistic regression, we calculated unadjusted odds of receiving timely treatment (< median time) versus more delayed treatment (≥ median time) as a function of age, language, ethnicity, insurance, Charlson comorbidity index, disease stage, method of first presentation (screening mammography vs care provider), symptoms at presentation, and type of surgical treatment. Results: Patients aged 55 to 64 years accounted for most of the sample (n=37; 35.2%). Median time from presentation to diagnosis (23 days), time from diagnosis to first treatment, and time from surgery to chemotherapy initiation fell within intervals published in the literature; median time from last surgery to start of RT was greater than recommended intervals. Factors significantly associated with longer intervals than median time included stage, method of presentation, language, surgical treatment, insurance, and ethnicity. Conclusions: Patients in this safety-net setting experienced acceptable diagnosis and treatment intervals, except for time to RT. Focused interventions that help care providers access imaging quickly for their symptomatic patients could improve time to diagnosis. Concentrating additional efforts on non–English-speaking, Hispanic patients and those who need to receive RT could improve time to treatment.

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Kamya Sankar and Brady L. Stein

Polycythemia vera (PV) and essential thrombocythemia (ET) are Philadelphia chromosome–negative chronic myeloproliferative neoplasms (MPNs), characterized by expansion of normal blood counts, bleeding, thrombosis, and the potential for transformation to myelofibrosis (MF) or acute myeloid leukemia (AML). The primary goals of treatment for MPNs are to reduce the risk of thrombosis, alleviate systemic symptom burden (eg, fatigue, pruritus, microvascular symptoms, and symptomatic splenomegaly), and to prevent transformation to MF/AML. Preventing transformation is clearly important, but not expected with current therapies. Currently, cytoreduction is advised based on vascular risk assessments, which include age and thrombosis history, as well as molecular profile in ET. Traditionally, cytoreduction has been advised only in patients with high vascular risk. Recently, a large prospective study evaluated the safety and efficacy of cytoreduction in patients with ET with less-than-high-risk vascular profiles. A larger question in the MPN field is whether cytoreduction is advisable for all patients with ET and PV, regardless of risk. This article reviews existing data on cytoreduction, evaluating hydroxyurea, interferons, and ruxolitinib in ET and PV. This review evaluates whether evidence supports a more liberal strategy of cytoreduction for all patients with ET and PV.