bluuebunny/crossref_metadata_2025 huggingface dataset:
The utilization of multidiciplinary tumor boards (MDT) in clinical routine: Results of a health care research study focusing on patients with metastatic colorectal cancer.
Authors: Homayounfar Kia , Lowes Markus , Kleiss Mathias , Lueck Rainer , Detken Sven , Nietert Manuel , Beissbarth Tim , Stanek Kathrin , Langer Claus , Ghadimi Michael , Conradi Lena-Christin
Published: March 2017

805

Background: Multidisciplinary Tumor Boards (MDT) have been advocated as standard of care in modern oncology. German cancer guidelines for metastasized colorectal cancer (mCRC) recommend discussing every patient (pt) with colon cancer (CC) after primary surgery and every pt with clinical stage IV CC as well as every rectal cancer (RC) pt prior to any therapy in a MDT. In this study we evaluated how extensive this approach has been implemented in clinical routine and how MDT discussion influences treatment decisions within a representative region with established access to MDTs for all actors. Methods: All major institutions treating oncological pts in southern Lower Saxony and Northern Hesse (N = 11) were invited to participate in the study. Pts with mCRC and diagnosis of the first metastasis between 01/2011 and 12/2013 were eligible. A standardized pt report form was developed and data were collected in a GCP-conform EDC-system named secuTrial. Results: A university medical center, 4 teaching hospitals, 1 communal hospital and 3 oncological focus practices participated in the study. In total, 470 pts (CC n = 278, RC n = 192) with a median age of 70 (range 22-92) years were enrolled. 286 (60.9%) pts had synchronous and 184 (39.1%) pts had metachronous metastases. Discussion within an MDT was performed in 141 (62.9%) of 224 CC pts after primary surgery and in 70 (38.3%) of 183 pts with clinical stage IV CC prior to any therapy. In RC pts, MDT discussion prior to any therapy happened in 91 (47.4%) pts. Curative resection of metastases was performed in 193 (41.1%) cases. Pts > 70 years (n = 250) received significantly more often chemotherapy ± surgery when presented in an MDT (85.8% versus 64.4%, p = 0.0002). In pts with single organ metastases the resection rate was not significantly different (48.4% versus 56.9%, p = 0.1574) but preoperative chemotherapy was more often indicated (56.7% versus 33.3%, p = 0.0056) when pts were discussed in a MDT. Conclusions: In clinical routine MDT discussion is not as established as advocated by national guidelines. Treatment decisions differ depending on MDT discussion especially in older pts and those with single organ metastases.
Maintenance treatment with capecitabine plus cetuximab after first-line standard fluorouracil-based chemotherapy plus cetuximab for patients with RAS wild-type advanced colorectal cancer.
Authors: Yuan Xianglin , Zhao Ben , Qiu Hong , Zhang Mingsheng , Zou Yanmei
Published: March 2017

806

Background: The optimum duration of first-line treatment with chemotherapy in combination with cetuximab (CET) in patients with RAS wild-type (wt) advanced colorectal cancer (ACRC) is unknown. The current study was designed to evaluate the efficacy and safety of maintenance treatment (MT) with capecitabine (CAP) plus CET in ACRC. Methods: The trial was conducted at Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, China. We included patients with previously untreated RAS wt ACRC, with stable disease or better after induction treatment with 4-6 months of standard fluorouracil-based chemotherapy plus CET, WHO performance status of 0 or 1. The selected patients were assigned to MT-CAP (1250mg/m2 orally twice daily on day 1-14 every 3 weeks), and CET (400 mg/m2 on day 1 of the first week, then 250 mg/m2 on day 1 every week). We assessed disease status every 6 weeks. The primary endpoint of the study was disease progression or unacceptable toxicity, defined as progression-free survival (PFS). All endpoints were calculated from the time of inclusion. Analyses were done by intention to treat. Results: From Jan. 1, 2014 to May 1, 2016, we assigned 13 patients to MT-CAP plus CET. Median follow-up time was 22 months. Median PFS was 16.7 months, and the PFS of MT was 12.1 months. MT was well tolerated, and none of the 13 patients discontinued treatment due to toxic effects. The general quality of life did not deteriorate during MT. Conclusions: MT-CAP plus CET after 4-6 months of standard chemotherapy and CET in ACRC patients was effective and did not compromise life quality. Based on these results, we launched a single arm, open-label, multi-center, Phase 2 clinical trial to investigate the efficacy and safety of MT-CAP plus CET after first-line standard fluorouracil-based chemotherapy plus CET for patients with RAS wt ACRC. The trial was registered with ClinicalTrials.gov, number NCT02717923, and approved by the Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Clinical trial information: NCT02717923.
Clinical significance of intratumoral HER2 heterogeneity (IHH) using endoscopic biopsy specimens in patients with HER2-positive gastric cancer (GC) who received T-mab-based chemotherapy.
Authors: Yagi Shusuke , Wakatsuki Takeru , Yamamoto Noriko , Chin Keisho , Takahari Daisuke , Ogura Mariko , Ichimura Takashi , Nakayama Izuma , Matsushima Tomohiro , Osumi Hiroki , Suenaga Mitsukuni , Ozaka Masato , Shinozaki Eiji , Ishikawa Yuichi , Yamaguchi Kensei
Published: March 2017

81

Background: We recently reported the clinical significance of IHH in trastuzumab (T-mab) based chemotherapy using surgical specimens; namely homogeneously HER2 positive GC was associated with longer survivals compared with heterogeneously HER2 positive GC (ASCO-GI 2015). However, three quarters of patients were diagnosed as having GC by endoscopic biopsy and no data are available as to whether IHH using endoscopic biopsy specimens predict T-mab efficacy. In this study, we addressed clinical usefulness of IHH using endoscopic biopsy specimens. Methods: Patients who received T-mab based chemotherapy and had endoscopic biopsy specimens available for IHC test were retrospectively examined. When all biopsy specimens which contained cancer cells were diagnosed HER2 IHC3+, it was defined as “Inter-specimens homogeneously HER2 positive (Inter-homo)”, and the others were defined “Inter-hetero”. When all tumor cells showed HER2 overexpressed within a specimen, it was defined “Intra-specimen homogeneously HER2 positive (Intra-homo), and the others were defined “Intra-hetero”. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods and compared using the log-rank test. Results: 57 patients were enrolled in this study. The median age was 67 years old and 70% were male. PS 0, GEJ cancer, intestinal type histology, and visceral metastasis (lung or liver) were found in 74% , 25% , 60% , and 53% , respectively. After the median follow-up period of 12.1 months, the median PFS and OS were 7.6 and 16.9 months, respectively. Significant survival differences were shown only in the comparison between inter-homo and inter-hetero; inter-homo group (n = 34) showed significantly longer PFS (8.5 vs. 5.1 months, HR 0.52 95%CI 0.27-0.98, p = 0.038) and OS (27.6 vs. 12.1 months, HR 0.27 95%CI 0.12-0.61, p = 0.001), respectively. Conclusions: Our data suggest that, in contrast to surgical specimens, the assessment of HER2 heterogeneity using endoscopic biopsy specimens may be useful for negative selection of patients who are unlikely to benefit from T-mab based chemotherapy.
A pilot study of apatinib reversing paclitaxel resistance in heavily pretreated advanced gastric cancer (AGC).
Authors: Lin Rongbo , Zhao Shen , Li Hui , Liu Jie , Fan Nanfeng
Published: March 2017

89

Background: In vitro or vivo, apatinib can reverse ABC-mediated multidrug resistance not only by inhibiting their transport function, but also by downregulating ABC expression. Methods: The patients with advanced gastric adenocarcinoma were resistant to paclitaxel-containing regimen (disease progression during or within 3 months after chemotherapy) and had measurable lesions received apatinib 850 mg, po, qd combined with paclitaxel alone (80 mg/m2 d1, d8, and d15, repeated 4-weekly) or POF (reported in 2007, 2008, 2009, 2010 ASCO, paclitaxel 135 mg/m2, oxaliplatin 85 mg/m2, and leucovorin 400 mg/m2, d1; 5-FU 2400 mg/m2 for 46h, repeat 2-weekly). The choice of regimen was left to clinician discretion in term of performance status and whether the agent that will be given has been resistant. Results: From 14th August 2015 to 1st March 2016, seven patients were eligible. The median age was 49 years (range, 43 to 67 years), 5 were males and 2 were females. The prior chemotherapeutic agents were summarized in table. Four patients had disease progression during apatinib. Two PRs, four SDs (unconfirmed), and one early death were observed. At a median follow-up of 238 days, the median progression-free survival was 124 days, the median survival was 194 days (range, 33 to 398+ days). Grade 3 to 4 neutropenia, anaemia, hypertension, fatigue, stomatitis was one patient respectively. No treatment-related death occurred. Conclusions: This study showed promising result that apatinib reverses paclitaxel resistance in heavily pretreated AGC. Clinical trial information: NCT02697838. [Table: see text]
NESC multicenter phase II trial in the preoperative treatment of gastric adenocarcinoma with chemotherapy (docetaxel-cisplatin-5FU + lenograstim) followed by chemoradiation (RTCT) based 5FU and oxaliplatin and surgery.
Authors: Mineur Laurent , Deplanque Gael , Desseigne Francoise , Moureau-Zabotto Laurence , Boulat Olivier , Jalali Khadifa , Smith Denis Michel , Obled Stephane , Belkacemi Mohamed
Published: March 2017

95

Background: Perioperative chemotherapy is a standard treatment. The combination of Docetaxel- cddp-5FU(DCF) is a treatment in metastatic gastric cancer with high response rate. Preoperative RTCT is expected to increase the rate of curative resections and complete histological response. We investigate the efficacy of an optimal chemotherapy with DCF + lenograstim then preoperative RTCT with oxaliplatin - 5FU in gastric adk. Methods: Between 2009 and 2014, 33 patients with gastric adenocarcinoma(adk) were included. Inclusion criteria adk of stomach, cardia, Siewert II, III, according to staging classification T2bT3T4anyNM0 optional laparoscopy. Treatment consisted of 2 cycles docetaxel 75 mg/m2 I.V. day 1, cddp 75 mg/ m2 I.V. day 1, 5-FU 750 mg/m2 continuous infusion for 120 h, every 3 weeks and lenograstim followed by RTCT delivered in 25 daily fractions of 1.8 Gy in 5 weeks with 5Fu 250mg/m2 continuous infusion per day on days 1 to 35 and oxaliplatin 85mg/m2 day 1-14-28. Surgery was performed 4-6 weeks after RTCT. The primary endpoints were pathological response rate and secondary PFS, overall survival, morbidity and post operative mortality, toxicity. Results: 33 patients were included, 1patient progressive disease(PD) after 2 cycles of DCF, 32 patients received RTCT and 2 patients PD after RTCT, 1 patient refused surgery. 29 patients were operated and 3 non resected (peritoneal metastasis). 26 patients underwent surgery after RTCT (total gastrectomy n = 12, total gastrectomy and diaphragm surgery n = 1 lewis santy n = 11, subtotal gastrectomy n = 1, Enlarged gastrectomy transverse colectomy and partial pancreatic n = 1 D1 (n = 5) and D2 (n = 21) R0 resection rate was n = 26/26. Postoperative morbidity (n = 12) and mortality (n = 2), histology mean nods examined and involved respectively 16 and 2,5. pT0pN0 23% pT1pN0 19% pTpN2N3 20% others 38%. < 10% residual tumor 27% histologic complete response 23%. Conclusions: Promising results from trials involving preoperative chemoradiation followed by surgery in gastric cancer need to be further evaluated in a Phase III and compared with perioperative CT. Clinical trial information: NCT01565109.
Phase 1 study of ZW25, a bispecific anti-HER2 antibody, in patients with advanced HER2-expressing cancers.
Authors: Hausman Diana Felice , Hamilton Erika Paige , Beeram Muralidhar , Thimmarayappa Jamuna , Ng Gordon , Meric-Bernstam Funda
Published: March 2017

TPS215

Background: HER2 is expressed above normal levels by many cancers, including a range of gastrointestinal tumors. While HER2 can contribute to tumor growth and survival even when expressed at low levels, antibody-based HER2 targeted therapy has shown efficacy only in breast (trastuzumab [T], pertuzumab [P]) or gastric cancers (T) with the highest levels of HER2 expression or gene amplification. Therefore, there remains significant medical need, particularly for cancers with lower HER2 levels or more heterogeneous patterns of expression. ZW25 is a novel humanized bispecific antibody directed against two distinct epitopes of HER2. The unique structure of ZW25 leads to greater cell decoration and receptor internalization than T, even in the setting of low levels of HER2 expression. In preclinical models, ZW25 has demonstrated greater activity than T in both HER2 high and HER2 low-expressing cancers, including gastric cancer. This first-in-human study will evaluate the safety and preliminary anti-tumor activity of ZW25 in patients with advanced HER2-expressing cancers. Methods: This is a 2-part Phase 1 study utilizing 3+3 dose escalation (Part 1) and expansion cohorts (Part 2) to evaluate the MTD, safety, PK, and anti-tumor activity of ZW25 IV once per week in patients with locally advanced, unresectable and/or metastatic HER2-expressing cancers. Eligibility requirements include any HER2 1+, 2+, or 3+ cancer (Part1) or 2+/FISH negative breast or gastric cancer (Part 2) that has progressed after all approved therapies; ECOG PS ≤ 1; normal left ventricular function; and measurable disease per RECIST 1.1 (Part 2). Assessments include collection of adverse events and laboratory abnormalities, tumor response per RECIST 1.1 and exploratory response biomarkers as well as PET. Recruitment is ongoing at 3 centers in the United States. Clinical trial information: NCT02892123.
A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of GS-5745 combined with mFOLFOX6 as first-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma.
Authors: Bendell Johanna C. , Starodub Alexander , Huang Xi , Maltzman Julia D. , Wainberg Zev A. , Shah Manish A.
Published: March 2017

TPS217

Background: GS-5745 is a monoclonal antibody that inhibits matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. Inhibiting MMP9 is expected to block paracrine signaling and metastasis and to alter the immune microenvironment within the tumor. GS-5745 (800 mg every 2 weeks) with mFOLFOX6 was examined in a Phase 1b study in 40 patients with gastric and GEJ adenocarcinoma (GS-US-296-0101), and demonstrated encouraging activity without added toxicity. Additionally, decreased serum biomarkers suggested inhibition of MMP9 enzymatic activity by these agents. These data support the hypothesis that GS-5745 treatment inhibits MMP9 activity and that the inhibition may lead to improved clinical outcomes. Methods: This phase 3, randomized, double-blind, multicenter study investigates the efficacy and safety of GS-5745 combined with mFOLFOX6 in subjects with untreated gastric and GEJ adenocarcinoma. Total of 430 eligible subjects with advanced gastric and GEJ cancer will be randomized in a 1:1 manner to mFOLFOX6 plus GS-5745 or mFOLFOX6 plus placebo. Stratification factors include ECOG status (0 v 1), geographic region (Latin America v All other countries), and primary tumor site (gastric v GEJ). CT or MRI scans will be performed every 8 weeks to evaluate response to treatment. mFOLFOX6 will be administered on Days 1 and 15 of each 28-day treatment cycle for a total of 6 cycles followed thereafter by leucovorin (LV) and 5-fluorouracil (5-FU) dosing on Days 1 and 15 of each 28-day treatment cycle until disease progression. GS-5745/placebo 800 mg will be infused on Days 1 and Day 15 of each 28 day cycle until disease progression. Primary endpoint is OS, and secondary endpoints include PFS, ORR (RECIST 1.1), and safety. The study is designed to have an 85% power to detect clinically meaningful improvement in overall survival at the one-sided significance level of 0.025. The association of exploratory biomarkers with study drug response will also be evaluated. Enrollment opened Oct. 2015. Clinical trial information: NCT02545504.
Prospective study of early detection of malignancies in individuals at risk for developing pancreatic cancer.
Authors: Snyder Courtney Edwards , Haag Susan , Adams Domenica , Paskett Breann , Hess Jade , Borazanci Erkut Hasan
Published: March 2017

TPS500

Background: It is estimated that by 2030 pancreatic cancer will be the second leading cause of cancer deaths in the US. Currently, only 9% of newly diagnosed pancreatic cancer is localized and 5-year survival is 7%. Due to most pancreatic cancers (PC) presenting at a later stage with poor overall survival, early detection methods must be implemented to improve treatment outcomes. Yet, effective early screening guidelines do not exist for pancreatic cancer. Our Early Detection Program (EDP) provides personalized early detection including risk assessment, screening, and genetic testing. We aim to evaluate risk assessment criteria, establish a database to delineate a pattern of characteristics, and utilize a biospecimen repository and molecular based technologies to map novel biomarkers for early detection. Methods: The EDP screens those with a family history or germline mutation consistent with potential increased risk for developing PC. Patients are eligible based on risk assessment and stratified into 3 groups based on the CAPS Consortium criteria (average, moderate, and high risk). Screenings may include genetic testing for germline mutations, blood testing including Hemoglobin A1C (HgBA1C), complete blood count (CBC), complete metabolic profile (CMP), cancer antigen 19-9 (CA 19-9), vitamin D 25-OH, lipid panel, and thyroid stimulating hormone (TSH). Serum and urine collection will be offered for banking for future studies. Patients have yearly screenings including thorough history and physical exam and cases are discussed at a multi-disciplinary pancreatic tumor board. If indicated, patients undergo MRI/MRCP abdomen, GI consult and EUS. Study participants also complete a cancer anxiety index. The EDP is still recruiting patients. Next-generation sequencing and molecular based technologies are being explored for mapping novel biomarkers for early detection. The Institute is expanding to include those at risk for breast and ovarian cancer. We are evaluating risk assessment criteria and are developing a valid and reliable EDP index (EDP-I) anxiety instrument.
Pilot skin microbiome study of patients with pancreatic cancer in comparison to patients with other malignancies as well as those without cancer.
Authors: Borazanci Erkut Hasan , Jameson Gayle S. , Hess Jade , Gelzayd Evan , Amini Sasan , Hosseini Dana , Von Hoff Daniel D.
Published: March 2017

TPS502

Background: The microbiome is a burgeoning field involving the study of the microbial flora in humans and its effect on health. The human microbiome is altered by several environmental factors and may play a great role in inflammation and possibly in the development in several malignancies including pancreatic cancer. The purpose of this study is to characterize the skin microbiomes on the forehead and cheek of people with pancreas cancer compared to people with other forms of cancer and people without cancer by utilizing the ProdermIQ skin profiling platform. Methods: This is a prospective, open-label, pilot study. Sampling will be done as one time collection after informed consent through a skin swab on the forehead and one on the cheek. Subjects with a diagnosis of pancreatic adenocarcinoma, subjects with a diagnosis of malignancy other than pancreatic adenocarcinoma, and subjects without a diagnosis of malignancy will be enrolled for three separate arms of the study. Each study arm is composed of 25 individuals for a total of 75. Key inclusion criteria include subjects at least 18 years of age and a histologically confirmed diagnosis of pancreatic adenocarcinoma in the pancreas arm; a histological confirmed diagnosis of a malignancy other than pancreatic cancer in the other cancer arm; and individuals without cancer. Individuals with a rash or skin disorder will be excluded from the study. Once all swabs are collected they will be batch tested through next generation sequencing to characterize the skin microbiomes. A comprehensive comparison will be constructed of the profiles of each study group.
KEYNOTE-224: Phase II study of pembrolizumab in patients with previously treated advanced hepatocellular carcinoma.
Authors: Zhu Andrew X. , Knox Jennifer J. , Kudo Masatoshi , Chan Stephen L. , Finn Richard S. , Siegel Abby B. , Ma Junshui , Watson Pat , Cheng Ann-Lii
Published: March 2017

TPS504

Background: The tyrosine kinase inhibitor sorafenib is the standard of care for first-line hepatocellular carcinoma (HCC). For patients with HCC after disease progression on sorafenib or for those with intolerance to sorafenib, no approved therapies are available. Because HCC is often driven by inflammation and is also associated with a suppressed immunoenvironment, there is a strong rationale to evaluate immunotherapy in patients with this type of cancer. The single-arm, multisite, phase 2 KEYNOTE-224 study (ClinicalTrials.gov, NCT02702414) was designed to evaluate the efficacy and safety of the anti–PD-1 antibody pembrolizumab in patients with previously treated advanced HCC. Methods: Approximately 100 patients will be enrolled. Inclusion criteria include age ≥18 years, histologically or cytologically confirmed diagnosis of HCC Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to or refractory to locoregional therapy, and disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation). Patients must also have measurable disease based on RECIST v1.1 as confirmed by central imaging vendor review, documented objective radiographic progression after stopping treatment with sorafenib or intolerance to sorafenib, Child-Pugh liver score A, ECOG performance status 0-1, and predicted life expectancy > 3 months. Patients will be allocated to receive pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles (~2 years) or until disease progression, unacceptable toxicity, patient withdrawal of consent, or investigator decision. Response will be assessed every 9 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. The primary end point is objective response rate per RECIST v1.1 by central imaging vendor review. Secondary end points are overall survival; safety and tolerability; and duration of response, disease control rate, time to progression, and progression-free survival per RECIST v1.1 by central imaging vendor review. Enrollment in KEYNOTE-224 is ongoing. Clinical trial information: NCT02702414.
A phase II trial of escalated dose proton radiotherapy with elective nodal irradiation and concomitant chemotherapy for patients with unresectable, borderline resectable, or medically inoperable pancreatic adenocarcinoma.
Authors: Nichols Romaine Charles , Morris Christopher G. , Hoppe Bradford S. , Rutenberg Michael Scott
Published: March 2017

TPS513

Background: The prognosis for patients with localized pancreatic adenocarcinoma who are not surgical candidates is poor. Median survival for patients with unresectable disease on the LAP-07 trial was between 15.2 and 16.4 months (Hammel P, et al. J Clin Oncol 31, 2013 [suppl; abstr LBA4003]). The absence of a survival advantage for x-ray based radiotherapy may be due to toxicity. Patients characterized as having “borderline resectable” disease fair somewhat better - although many are not converted to resectability with standard regimens. Intensified local/regional therapy for "initially unresectable" patients might 1.) Increase the share of patients undergoing curative surgery and 2.) Improve local disease control for patients who remain unresectable. A phase II study for patients with unresectable disease treated with proton therapy to a dose of 59.4 Gy (RBE) demonstrated an 18.4 month median survival without grade 2 or higher GI toxicity – suggesting the feasibility of dose intensification (Sachsman S, et al. Int J Particle Ther. 2014;1[3]:692–701.). The current protocol offers a 6% increase in radiotherapy dose with a 25% increase in dose per fraction with the goal of improving local control and extending survival. Methods: Eligibility: Biopsy proven adenocarcinoma of the pancreas that is unresectable, borderline resectable, or medically inoperable. No evidence of metastatic disease. Prior chemotherapy allowed. Treatment: 40.50 Gy (RBE) in 18 fractions to gross disease and an elective nodal volume followed by a 22.50 Gy (RBE) in 10 fraction boost to gross disease (total dose 63 Gy [RBE] in 28 fractions) with concomitant capecitabine (1,000 mg PO BID) on radiation treatment days. Surgery between 8 and 16 weeks of radiotherapy completion if radiographic studies suggest operability. Primary Objective: Improve 12 month survival from 50% to 75%. Secondary Objectives: Improve local and regional disease control Increase share of patients being converted to resectable. Compare GI toxicity with historical benchmarks. Assess quality of life. Sample Size:60 patients Clinical trial information: 02598349.
A pilot-blinded randomized feasibility trial comparing an investigational hand therapy intervention (IHT) to a traditional occupational therapy (TOT) intervention to prevent chemotherapy induced peripheral neuropathy (CIPN) of the hands in patients (pts) receiving chemotherapy (CTX).
Authors: Jameson Gayle S. , Cooper Cynthia , Borazanci Erkut Hasan , Hull Lynne , Caldwell Lana , Von Hoff Daniel D.
Published: March 2017

TPS518

Background: CIPN is an unsolved, common problem for cancer pts. CIPN greatly affects quality of life and may impact quantity of life due to dose reductions and discontinuation of beneficial therapy. No generally accepted evidence-based prevention strategies for CIPN exist. In the discipline of hand therapy (HT), there are effective science-based interventions to treat peripheral neuropathies due to injury and disease. These interventions have not been explored in patients with CIPN. Methods: Study objective is to determine if an IHT intervention based on concepts of neuroplasticity can prevent or delay time to onset of CIPN of the hands as measured by Patient Reported Outcomes & Criteria for Adverse Events, version 4 (CTCAE 4.0), compared to a TOT intervention. Eligible pts have pancreatic cancer and receive nab-paclitaxel + gemcitabine containing combinations; have no prior evidence of peripheral neuropathy (PN) of the hands and are not taking duloxetine or gabapentin. Randomization is 1:1. Patient instructions on the blinded IHT or TOT activities are done by an Occupational Therapist prior to start of CTX, then reinforced at multiple follow-up sessions. Periodic assessments include standardized hand sensibility testing: QuickDASH, upper extremity provocative testing, TEN Test; plus pt reporting of CIPN onset, CTCAE-4, physical examination of peripheral sensory/motor neurologic assessment of the hands, Karnofsky Performance Status, and pain visual analogue scale. Participation in the study with a daily home program continues until onset of CIPN of the hands or if no CIPN then through completion of an 84 day schedule of chemotherapy. The number and proportion of patients without CIPN of the hands at the end of 84 days of CTX will be summarized for both intervention groups. For an 80% powered design with a medium effect size, 40 evaluable pts are needed (95% CI, alpha .05). Planned enrollment is up to 50 pts allowing for pt attrition. Study opened to enrollment 8/2016.
Identifying models of cancer survivorship care.
Authors: Mead Holly , Pratt-Chapman Mandi , Gianattasio Kan , Cleary Sean , Gerstein Maya
Published: March 2017

1

Background: The growing population of cancer survivors (15.5 million in the US) face myriad health issues that require health care attention. Cancer is increasingly viewed as a chronic illness that, once treated, requires systematic and coordinated care. Little guidance, however, has been provided in terms of how programs should be organized and little research has been done to understand emerging models in the field. We aim to identify and describe the most common survivorship models of care to identify characteristics of care and provide guidance on how survivorship care should be delivered. Methods: We conducted a scan of 236 CoC-accredited cancer centers to identify characteristics that co-occur in survivorship programs and those that predict the provision of LIVESTRONG’s Essential Elements. We supplemented this approach with in-depth interviews and surveys of 32 survivorship programs to gain detailed organizational information. Results: Three models emerged from the data: The Consultative Specialized Survivorship Clinic provides a one-time onsite visit focusing on in-depth survivorship care planning and is typically led by an NP/PA. It is likely to enjoy more organizational support and to bill for services. The Longitudinal Specialized Survivorship Clinic provides ongoing care with most services delivered onsite, and is typically led by an NP/PA. It is likely to have some organizational support but less likely to bill for services. Oncology-Based Survivorship Care with Referral for Services provides ongoing survivorship care, often in tandem with treatment, but delivers most services via referral. It is typically physician-led and has no formal survivorship care planning protocol. It receives less organizational support and is less likely to bill for services. Models also differ in the numbers and types of services provided. Conclusions: These models reflect distinctive organizational and delivery system characteristics and can guide other institutions interested in providing survivorship care.
Financial impact of cancer care on survivors: Results from the 2015 LIVESTRONG survey.
Authors: Narayan Aditi
Published: March 2017

10

Background: The cost of cancer care in the U.S. was $124.5 billion in 2010, and is projected to increase by 27% to $158 billion in 2020. With an estimated 1.7 million new cancer cases every year, it is imperative to understand the financial impact of cancer care on survivors’ decision-making and daily living. Methods: In August of 2015, LIVESTRONG conducted an online survey to learn more about the financial impact of treatment on cancer survivors and their loved ones. Two similar surveys were distributed for survivors (n = 1,704) and loved ones (n = 739). Our analyses focus on the results from the survivor survey. Results: Fifty-nine percent of survivors reported that they experienced a lot of or some financial problems as a result of cancer. Eighty-five percent of survivors reported that their provider did not discuss the costs of care with them, and 12% reported that they would have altered decisions about treatment if they had known then what they know now about the financial impact of cancer. Most survivors (59%) reported that they spent less than $10,000 on out-of-pocket costs while 27% reported that they spent between $10,000 and $24,999 on out-of-pocket costs. The majority of respondents reported that they paid out-of-pocket for doctor visit co-pays (77%), transportation (60%) and medications (51%) (Table 1). Additionally, 61% of survivors reported that they had to make financial sacrifices such as using retirement savings and spending less on day-to-day living expenses. Conclusions: With costs of cancer care expected to continue rising for the foreseeable future, there is a need for more and better communication between patients and healthcare teams related to the potential financial impact of cancer care prior to treatment. Cancer institutions should consider including financial counselors as a part of care teams to inform patients of costs based on insurance status and type, and help them make educated and well-informed decisions related to their care. [Table: see text]
Chest CT findings among adult survivors of childhood and young adult cancer with a history of chest radiation.
Authors: Tonorezos Emily S. , Barnea Dana , Khan Amber , Chou Joanne F. , Moskowitz Chaya S. , Kaplan Rana , Oeffinger Kevin C.
Published: March 2017

103

Background: While survivors of childhood and young adult cancer with a history of radiation therapy (RT) to the chest are known to be at increased risk for lung cancer, whether a CT-based lung cancer screening program is appropriate for this population is unknown. We sought to describe CT findings in a clinic-based population of childhood and young adult cancer survivors. Methods: We performed a detailed review of all diagnostic chest CT scans performed among patients seen in the Adult Long-Term Follow-Up Program at Memorial Sloan Kettering between August 2005 and May 2016. Included survivors were at least 5 years from diagnosis and had a history of RT to the mediastinum, mantle, axilla, lung, thoracic spine, or total body irradiation fields. Results were reviewed by at least two authors (ET, DB, or AK) and discrepancies were resolved by consultation with a pulmonologist (RK). Results: We identified 620 survivors with a history of chest field RT who were at least 5 years from diagnosis. The population was 48% male, with a median age at diagnosis of 17.2 years. Approximately half were survivors of Hodgkin Lymphoma (N=306; 49.5%) and almost one-third had undergone hematopoietic cell transplant (N=188; 31%); other diagnoses included non-Hodgkin Lymphoma and sarcoma. The most frequently cited RT field was mantle (N=219; 36%), followed by total body irradiation (N=142; 24%) and whole lung (N=110;18%). Among 351 survivors with at least one chest CT, 206 (59%) had at least one pulmonary nodule, 174 (50%) had fibrosis, and 132 (38%) had a ground glass opacity. Among those with a pulmonary nodule, the large majority (91% of those with a nodule) were followed expectantly or underwent repeat imaging; these patients were spared biopsy or resection. Among 18 patients who underwent biopsy, wedge resection, fine needle aspiration, or bronchoscopy, 4 were diagnosed with lung adenocarcinoma, 3 with metastatic sarcoma, and one with marginal zone lymphoma (MALT). Conclusions: Benign pulmonary nodules among adults with a history of RT for childhood or young adult cancer are common. Any strategy for lung cancer screening in this population will need to account for a high likelihood of benign findings on chest CT.
Total and cancer-attributable phase-based costs for childhood cancer care: A population-based study in British Columbia, Canada.
Authors: McBride Mary L , Duncan Ross , Bremner Karen , De Oliveira Claire , Liu Ning , Nathan Paul C. , Rogers Paul C. , Peacock Stuart , Krahn Murray Dale
Published: March 2017

11

Background: Childhood cancer presents unique issues regarding treatment, late effects, and long-term survival, but few studies have reported costs. Childhood cancer-specific costs are useful for economic evaluation and planning care. This study estimates total and cancer-attributable (net) medical costs for a population-based childhood cancer cohort in British Columbia, Canada, by phase of care. Methods: Patients diagnosed with cancer at ages 91 days to 14 years between 1995-2009 were identified from the British Columbia Cancer Registry, and followed to December 31, 2010. Data were linked with clinical and provincial administrative healthcare databases covering all medically-necessary costs. Total resource-specific costs (Canadian $ 2012) were estimated overall and for patients with leukemia, lymphoma, central nervous system (CNS), and “other” cancers. Net costs were calculated by subtracting healthcare costs for propensity-score-matched provincial samples of children without cancer from cancer patient costs. Results: Of the 1,440 cases, 33% had leukemia, with 23% CNS tumours, 10% lymphoma, 34% other cancers; 93% survived >=1 year. Overall pre-diagnosis mean costs per patient were $4,633, of which $4,555 was attributable to the cancer. Overall initial (first-year) mean costs were $97,780 ($97,254). Overall continuing phase mean costs were $12,441 ($12,006). Overall final year of life mean costs were $284,201 ($283,652). Cancer types with highest costs were CNS (pre-diagnosis), leukemia (first-year), “other” cancers (continuing), and lymphoma (end-of-life). Virtually all inpatient hospitalizations were cancer-related, representing ~41% of pre-diagnosis, ~71% of first-year, ~57% of continuing, and ~73% of end-of-life costs. Conclusions: Management of childhood cancer is costly, and is higher than for adolescent cancer in all phases of care, reflecting greater morbidity and treatment complexity. Hospitalizations were the largest driver of costs in all post-diagnosis phases of care. Costs in the continuing phase, including surveillance and care for late effects, were 13% of first-year phase costs.
Increased late mortality in underweight survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: Tonorezos Emily S. , Meacham Lillian R. , Chou Joanne F. , Moskowitz Chaya S. , Leisenring Wendy M. , Friedman Danielle Novetsky , Sklar Charles A. , Dilley Kimberley Jo , Hudson Melissa M. , Mertens Ann C , Armstrong Gregory T. , Robison Leslie L. , Oeffinger Kevin C.
Published: March 2017

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Background: Approximately one-in-ten adult survivors of childhood cancer are underweight. While the consequences of being overweight or obese have been well-described, outcomes among underweight childhood cancer survivors are unknown. Methods: Underweight was defined as a body mass index (BMI)< 18.5 kg/m2, calculated from self-reported height and weight on either the baseline or the first follow-up questionnaire from the Childhood Cancer Survivor Study (CCSS). National Death Index provided death data and self-reported subsequent malignant neoplasm were validated by pathology report. Chi-square test was used to examine the association between underweight status (< 8.5 kg/m2 vs ≥ 18.5 kg/m2) and baseline demographic characteristics. Marginal models with generalized estimating equations were used to evaluate the associations between BMI and outcomes. Results: Of 9454 survivors (median age 35 years old, range 17-58, with an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline and had at least two years of additional follow-up. 29 of 184 deaths were among underweight survivors. In univariate analysis, underweight status was more common among females (9.1% vs 4.5 %, p<0.01) and participants with younger age (8.2% for <5 yrs vs. 6.1% for >=5yr, p<.01), lower household income (8.9% for <$20,000 vs. 6.0% for >=$20,000, p<0.01), and a history of a grade 3 to 4 chronic condition (p = 0.05). After adjustment for these factors, in addition to race/ethnicity, prior smoking, and a history of radiation therapy, the odds of all-cause mortality within two years of BMI report was 2.82 (95% CI: 1.64-2.2; p<0.01) for underweight survivors, compared to normal weight survivors. The risk of subsequent malignant neoplasms within two years of BMI report among underweight survivors compared to normal weight survivors was not significantly increased (OR 1.31; 95% CI: 0.60-2.85; p = 0.49). Conclusions: Childhood cancer survivors who are underweight are at significant risk for late mortality that is unrelated to smoking status, chronic illness, or second malignancy. Whether targeted nutritional interventions would ameliorate this risk is unknown.
Changes in arm tissue composition with slowly-progressive weight-lifting among women with breast cancer-related lymphedema.
Authors: Zhang Xiaochen , Brown Justin C. , Paskett Electra D. , Zemel Babette , Cheville Andrea L. , SCHMITZ KATHRYN H.
Published: March 2017

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Background: We evaluated baseline differences in arm tissue composition (fat mass, lean mass, bone mineral content [BMC] and bone mineral density [BMD]) between the affected and unaffected arms in women with breast cancer-related lymphedema (BRCL). We compared changes in arm tissue composition and self-reported lymphedema symptoms after one-year of weight-lifting vs. usual-care. Methods: We utilized data from the PAL trial that included 141 women with BRCL. Arm tissue composition was quantified using dual-energy x-ray absorptiometry. The severity of lymphedema was quantified using self-report survey. Weight-lifting was performed at community fitness facilities. Results: At baseline, the affected arm had more fat (D= 89.7±21.0g; P < 0.001) and lean mass (D= 149.1±25.3g; P < 0.001), but less BMC (D= -3.2±0.9g; P < 0.001) than the unaffected arm. No difference was observed in BMD. After 12-months of weight-lifting, composition of the affected arm was improved: lean mass (71.2±27.9g; P = 0.01) and BMD (0.01±0.01g; P = 0.02) increased, arm fat percentage decreased (0.01±0.01; P = 0.003). No changes observed in fat mass and BMC. Baseline body mass index and BCRL grade modified the relationship between weight-lifting and tissue composition changes. Increases in lean mass were associated with less severe BCRL symptoms. With every one-percent decrease in arm fat percentage, affected limb volume reduced 13.81mL. Conclusions: Among women with BRCL, affected and unaffected arms differ in tissue composition. These differences may be improved with weight-lifting. Changes in arm tissue composition correlate with improved BCRL symptoms. Investigating the combined effects of exercise and weight-loss on arm tissue composition and BCRL symptoms may provide additional insight to the benefits of lifestyle modification on lymphedema biology. Clinical trial information: NCT00194363.
Long-term outcome of patients with lower extremity Ewing sarcoma.
Authors: Ranft Andreas , Winter Corinna , Hoffmann Christiane , Rosenbaum Dieter , Rossig Claudia , Juergens Herbert , Dirksen Uta
Published: March 2017

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Background: With improved survival rates of patients with Ewing sarcoma the quality of long-term survivorship needs to be addressed. In this study, general recovery and restitution of function following intensive bone tumor treatment were analyzed by assessing the clinico-functional outcome and physical activity using self-reporting and objective measurement tools. Methods: Long-term outcome of 224 former patients with lower extremity Ewing sarcoma, registered between 1980 and 2009 in consecutive clinical trials of the GPOH, were assessed using the TESS, SF-36, BSI, and RSES questionnaire scales, and the accelerometric StepWatch Activity Monitor (SAM). To compare results with healthy subjects, 111 non-random peer controls were selected. Median observation time was 13.8 years from primary diagnosis (range 4.1-31.2). Results: Absolute values from the questionnaire scores indicated no major clinical findings in former patients. Compared to controls, unfavorable outcomes were however seen on physical TESS (d=-0.85), PCS (SF-36) (d=-1.08) and BSI-S scores (d=0.65) (P<0.001), in contrast to mental MCS (SF-36), BSI-A, BSI-D, RSES scores (d<0.40). Former patients were less active than the control group (10067 vs. 12430 steps per day; d=-0.56; P<0.001), but on average did reach the recommended level for an active life-style (>10000 steps). Comparing local therapy modality, physical scores for SAM, TESS, PCS were 10978, 91.2, T=50.2 for patients treated with surgery (N=101), 11097, 90.0, T=48.6 in patients with combined modality treatment (N=108), and 10093, 92.8, T=50.0 for patients with definite radiotherapy (N=15) (P=0.648; P=0.580; P=0.368). Conclusions: Survivors of primary lower extremity Ewing sarcoma exhibited moderately reduced self-reported and objectively measured physical outcome scores. Continuous long-term observation will be important in order to identify disease-specific prognostic factors for these patient-oriented outcomes.
Prospective surveillance using l-dex monitoring results in significant reductions in the chronic rate of breast cancer related-lymphedema (BCRL) in high-risk breast cancer patients.
Authors: Laidley Alison L. , Anglin Beth V.
Published: March 2017

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Background: Survivorship represents an increasing focus in the management of breast cancer with chronic toxicities including breast cancer-related lymphedema (BCRL). This study looked at prospective surveillance using bioimpedance spectroscopy (BIS) to reduce risks of chronic BCRL requiring referral for complete decongestive therapy (CDT). Methods: 132 patients at high-risk for the development of BCRL were prospectively followed using BIS with serial monitoring. This included a pre-operative baseline assessment and a minimum of two post-operative follow up assessments. Interventions were initiated when the L-Dex score increased by greater than 10 units from baseline and consisted of conservative treatment with a compression sleeve for four weeks. Patients were also clinically monitored for the development of BCRL. Results: Median follow-up was 19.3 months (range 4-54 mos). Of the 132 patients evaluated, 24 (18.1%) were subsequently diagnosed with elevated L-Dex scores and underwent intervention. Of the 24 that underwent treatment, 14 (58%) had resolution of their elevated L-Dex scores following four weeks of therapy with 10 having persistent elevations and clinical BCRL which necessitated referral to physical therapy for CDT. A further 7 subjects were diagnosed and not treated for elevated L-Dex scores, but had complete resolution (return to baseline) at last visit. At last follow-up, only 10 patients (7.6 %) had unresolved, clinical stage 1, BCRL. Conclusions: The use of L-Dex to prospectively follow our high-risk patients and prescribe intervention with a compression sleeve for 4 weeks when scores are elevated resulted in only a 7.6 % rate of stage 1, chronic BCRL. This rate of BCRL has been reported as 15-20%, suggesting that a prospective program of screening and intervention using L-Dex does result in clinically meaningful reductions in this long-term sequelae of treatment.