bluuebunny/crossref_metadata_2025 huggingface dataset:
Checkmate 649: A randomized, multicenter, open-label, phase 3 study of nivolumab (Nivo) plus ipilimumab (Ipi) versus oxaliplatin plus fluoropyrimidine in patients (Pts) with previously untreated advanced or metastatic gastric (G) or gastroesophageal junction (GEJ) cancer.
Authors: Janjigian Yelena Yuriy , Adenis Antoine , Aucoin Jean-Sebastien , Barone Carlo , Boku Narikazu , Chau Ian , Cleary James M. , Feeney Kynan , Franke Fabio Andre , Moehler Markus , Roca Enrique Luis , Schenker Michael , Li Mingshun , Ajani Jaffer A.
Published: March 2017

TPS213

Background: The combination ofoxaliplatin and fluoropyrimidine is a standard-of-care (SOC) first-line treatment of pts with metastatic G/GEJ cancer, resulting in a median overall survival (OS) of 8–11 months and objective response rate (ORR) of 30%–50%. This is accompanied by up to 77% grade 3/4 toxicities. Therefore, new treatment options are needed to improve survival and decrease toxicity in G/GEJ cancer. Nivo, a fully human IgG4 monoclonal antibody (mAb) that targets programmed death 1 (PD-1) and ipi, a fully human IgG1 mAb that targets cytotoxic T-lymphocyte–associated protein 4, have demonstrated manageable safety profiles and efficacy in multiple tumor types and may have a synergistic effect. In a phase 1/2 study in chemotherapy-refractory pts with G/GEJ/esophageal cancer with or without PD-1 ligand 1 (PD-L1) expression, second-line nivo 1 mg/kg + ipi 3 mg/kg demonstrated a manageable safety profile and resulted in 26% ORR (44% ORR in pts with PD-L1+ tumors), median OS of 6.9 months, and a 34% OS rate at 12 months (Janjigian Y, et al. J Clin Oncol. 2016;34[suppl][abstract 4010]). This open-label, phase 3 trial will evaluate nivo + ipi as first-line therapy for pts with G/GEJ cancer (CheckMate 649; NCT02872116). Methods: In this study, 870 pts aged ≥ 18 years with untreated advanced or metastatic G/GEJ cancer with or without PD-L1 expression will be randomized to receive nivo + ipi (4 doses; followed by nivo monotherapy) or investigator’s choice of capecitabine/oxaliplatin (XELOX) or fluorouracil/leucovorin/oxaliplatin (FOLFOX). Tumor tissue for determination of PD-L1 status must be provided from ≤ 6 months before study treatment. Pts receiving chemotherapy or radiotherapy for G/GEJ cancer within the last 6 months or pts with suspected autoimmune disease, uncontrolled medical disorder, or active infection are excluded. Primary endpoint is OS in pts with PD-L1+ tumors. Secondary endpoints include OS in all pts and progression-free survival and time to symptom deterioration in all pts and pts with PD-L1+ tumors. Clinical trial information: NCT02872116.
Use of circulating tumor DNA levels to gauge necessity of surgery for patients undergoing trimodality therapy for esophageal cancer.
Authors: Nabavizadeh Nima , McLaren Patrick James , Melendez Daira , Halsey Carol , Lopez Charles D. , D'Souza Sharlene , Enestvedt Brintha , Dolan James P. , Thomas Charles R. , Spellman Paul
Published: March 2017

TPS214

Background: Up to 40% of patients receiving neoadjuvant esophageal chemoradiotherapy (CRT) are found to have no evidence of malignancy post-operatively. Given this, a sensitive and specific biomarker is needed, as reliable identification of complete responders may spare patients the morbidity and mortality of esophagectomies. Recent work with circulating tumor DNA (ctDNA) collected from the plasma of cancer patients indicates tumors routinely shed large amounts of DNA into the blood. This ctDNA can be systematically analyzed, quantification of which has been correlated with local and systemic disease burden. To further increase the specificity of analysis, the somatic mutations that arose in the tumor can be detected in ctDNA via targeted and whole genome sequencing. However, information on the feasibility of using ctDNA quantification as a biomarker for neoadjuvant response assessment is lacking. We hypothesize that quantification of ctDNA throughout trimodality therapy can be of practical use in the non-invasive monitoring of treatment response. The overall goal of this pilot project is to assess the feasibility and predictive utility of incorporating a sensitive, patient and tumor specific, plasma ctDNA quantification assay to more reliably identify complete responders following CRT. The long-term goal of this proposal is to apply these methods into prospective clinical trials for personalization of therapy by identifying neoadjuvant complete responders who may benefit from non-operative therapy. Methods: Pilot/feasibility study to evaluate the correlation between plasma ctDNA levels and pathologic treatment response. Plasma samples at different treatment time points (pre-CRT, during CRT, immediately pre-op and post-op) will be collected from 28 patients receiving pre-operative CRT followed by surgery for esophageal cancer. Patient-specific mutations will be identified through whole exome sequencing of paraffin-embedded pre-treatment biopsies. SafeSeqS PCR primers will be designed per patient for targeting of tumor mutations. Plasma-derived ctDNA will be assayed using the patient-specific SafeSeqS approach for each time point in triplicate.
Phase 1b dose-escalation and cohort-expansion study of the safety, tolerability, and efficacy of a novel transforming growth factor-β receptor I kinase inhibitor (galunisertib [G]) administered in combination with the anti-PD-L1 antibody (durvalumab [D]) in recurrent or refractory metastatic pancreatic cancer.
Authors: Melisi Davide , Guba Susan C. , Karasarides Maria , Andre Valerie
Published: March 2017

TPS501

Background: Transforming growth factor-β (TGF-β) can suppress adaptive and innate anti-tumor immune responses. G (LY2157299) is an oral small molecule inhibitor of TGF-β receptor I kinase that down-regulates phosphorylation of SMAD2, abrogating activation of the canonical pathway. Programmed cell death-ligand 1 (PD-L1) is upregulated in a broad range of cancers including pancreatic; expression of PD-L1 helps tumors evade immune system detection through binding to PD-1 on cytotoxic T lymphocytes. D (MEDI4736) is an anti-PD-L1 monoclonal antibody that blocks PD-L1/PD-1 interactions. Blockade of both TGF-β and PD-L1 pathways could reverse immunosuppression associated with these molecules by activating adaptive and innate anti-tumor immune responses. Methods: This two part phase 1b open-label study will enroll patients (pts) with recurrent or refractory metastatic pancreatic cancer. Part 1 is a 3+3 dose-escalation assessment of the safety and tolerability of G (4 escalating doses) and D (constant dose). After dose-limiting toxicity evaluation, cohort expansion with approximately 25 pts at the dose determined in the dose escalation portion will occur. Eligible pts have recurrent or refractory metastatic pancreatic cancer ( ≤ 2 prior systemic regimens) regardless of PD-L1 status; ECOG PS 0-1. Pts who have received prior therapy targeting T-cell costimulation or checkpoint pathways, or have received a TGF-β R1 kinase inhibitor are not eligible. Pretreatment and on-treatment biopsies will be obtained. The primary objective is to assess safety and tolerability of G in combination with D by identifying dose-limiting toxicities and to assess safety of the combination at the dose-escalation-established dose. Secondary objectives are pharmacokinetics; immunogenicity; preliminary anti-tumor activity; overall survival. Exploratory objectives are to examine biomarkers relevant to G, D, and the disease state. Enrollment began on 15-June-2016; as of 13-Sep-2016, 1 pt entered treatment. Clinical trial information: NCT02734160.
A randomized controlled trial to compare the effectiveness between surgery and radiofrequency ablation for hepatocellular carcinoma: SURF trial.
Authors: Hasegawa Kiyoshi , Kokudo Norihiro , Matsuyama Yutaka
Published: March 2017

TPS506

Background: Which is superior to treat hepatocellular carcinoma (HCC), surgery or percutaneous ablation? This has been one of the most important questions in clinical research of hepatology. However, it has long remained unanswered because it is difficult to approach, as we mentioned previously (Ann Surg 2008;247:557-8). Thus, in 2009, we started this multicenter study in Japan to reach a strong conclusion to the above question (UMIN:000001795). Methods: The major inclusion criteria are: tumor foci numbering three or fewer, and each measuring 3 cm or less); Child–Pugh score of 7 or less; aged between 20 and 79 years; and indications for either surgical resection or radiofrequency ablation (RFA), as described previously (Hepatol Res 2010;40:851-2). In the study design, we adopted two co-primary end-points: overall survival (OS) and recurrence-free survival (RFS). If assuming 3-year RFS following surgery and RFA are assumed as 45% and 35%, respectively, 600 cases are regarded as necessary. Because 600 cases would be also sufficient to detect 10% difference in OS, the target number of cases was set as 600. However, the recruitment was very difficult. The Independent Data Monitoring Committee recommended us to transiently stop the recruitment at the end of August 2015 when the number of the registered cases reached 308. At submission of this abstract, we are considering whether the current number (308) is enough or not to detect 10% difference in RFS by calculating conditional predictive power. We will describe the trial design, and the current situations in detail for debate. Clinical trial information: UMIN:000001795.
Phase Ib/II study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer.
Authors: Acoba Jared David , Rock Amy , Wong Hing C.
Published: March 2017

TPS510

Background: IL-15 is one of the most promising new candidates in cancer immunotherapy. Similar to IL-2, IL-15 stimulates natural killer (NK) and CD8+ T cells, however IL-15 may be a more effective and safer therapy as it does not trigger regulatory T cells or induce capillary leak syndrome. Preclinical data also show that IL-15 is effective in eradicating murine pancreatic cancers. However, the use of rhIL-15 in the clinic however has been limited by its short half-life (30 minutes) and cytokine related adverse effects, such as fever and hypotension. Compared with IL-15, ALT-803, a novel IL-15 superagonist complex (IL-15N72D:IL-15RαSu/Fc), has a prolonged serum half-life and is capable of potently inducing NK and CD8+ T cell proliferation in vivo. Pancreatic cancer remains one of the most common causes of cancer death and novel therapies are needed. This study represents the first clinical experience of ALT-803 in the treatment of pancreatic cancer. Methods: This is a Phase Ib/II, multi-institution study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer. The study involves a phase Ib dose escalation phase to determine the MTD using a standard 3+3 design. Patients will receive gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2 D1, 8, 15 and ALT-803 at assigned dose on D2, 9, 16 of a 28d cycle. Primary endpoints are safety and tolerability. Phase II will be a two-stage expansion phase using a Simon two-stage design with a primary endpoint of survival at 8.5 months. Secondary endpoints include response rate, progression free survival, and overall survival. Response will be assessed q8 weeks by RECIST v1.1. Major inclusion criteria include: locally advanced (Phase Ib only) or metastatic pancreatic adenocarcinoma, adequate organ function, PS ECOG 0-2, and 0 or 1 (Phase Ib only) line of prior therapy for advanced pancreatic cancer. Prior nab-paclitaxel is not allowed Current enrollment: Enrollment to the first dose level is ongoing. Complete accrual of phase Ib is expected within nine months. Clinical trial information: NCT02559674.
A phase II pilot trial of nivolumab + albumin bound paclitaxel + paricalcitol + cisplatin + gemcitabine (NAPPCG) in patients (pts) with previously untreated metastatic pancreatic ductal adenocarcinoma.
Authors: Borazanci Erkut Hasan , Jameson Gayle S. , Borad Mitesh J. , Ramanathan Ramesh K. , Korn Ronald Lee , Caldwell Lana , Ansaldo Karen , Hendrickson Kristin , Von Hoff Daniel D.
Published: March 2017

TPS511

Background: Despite decades of basic and clinical research, effective therapy for the treatment of patients with pancreatic ductal adenocarcinoma (PDAC) remains one of the greatest unmet clinical needs in oncology today. Albumin-bound paclitaxel (AP) and gemcitabine (G) reported on an improvement in overall survival in metastatic (m) PDAC [NEJM 2013; 369:1691-1703]. The addition of cisplatin (C) has shown promising clinical data in previously reported studies [Cancer Res 2015; 75(15 Suppl):Abstract nr LB-003]. Through further preclinical work, vitamin D analog therapy decreases myeloid derived suppressor cell (MDSC) and regulating T cells (Tregs) thus turning PDAC into a more immune friendly microenvironment. This trial combines AP/C/G with the vitamin D analog paricalcitol (P) and the antibody-PD-1 drug Nivolumab (N) as a combination therapy for individuals with previously untreated metastatic PDAC. This trial evaluates the efficacy and safety of NAPPCG in patients in that population (NCT02754726). Methods: Key eligibility criteria include Stage IV PDAC, no prior chemotherapy for systemic disease, KPS ≥ 70; life expectancy ≥ 12 weeks and measurable disease. Key exclusion criteria include prior PD-1 or PD-L1 therapy. Doses are AP 125 mg/m2 undiluted, G 1000 mg/m2 in 500 ml of normal saline (NS), each infused over 30 minutes with C 25mg/ m2 in 500 ml of NS infused over 60 minutes on days 1, 8, 22, and 29 of a 42 day cycle. N is given at a fixed dose of 240 mg as a 60 minute infusion on days 1, 15, and 29. P is given at a fixed dose of 25 µg IV on days 1,4,8,12,15,22,26,29,32,36,and 39. Primary objective is to determine the efficacy of the combination NAPPCG for patients with previously untreated metastatic PDAC through determining CR, ORR, PFS, and OS. The secondary objective is to evaluate the safety of NAPPCG in patients with previously untreated metastatic PDAC. The study initiated accrual in April of 2016. If 4 of the first 10 patients are determined to have a PR the trial will expand to a total of 25 patients. Clinical trial information: NCT02754726.
Phase I study of definitive chemoradiation with gemcitabine and the WEE1 inhibitor AZD1775 in unresectable pancreatic cancer.
Authors: Cuneo Kyle Clifford , Morgan Meredith , Schipper Matthew J , Maybaum Jonathan , Al-Hawary Mahmoud , Simeone Diane M. , Sahai Vaibhav , Zalupski Mark , Lawrence Theodore Steven
Published: March 2017

TPS512

Background: Targeting cell cycle checkpoints has the potential to enhance the efficacy of chemoradiation therapy. Tumor cells commonly have an abnormal G1 checkpoint due to mutations in the p53 pathway making them reliant on the G2 checkpoint to repair DNA damage. In our preclinical studies, WEE1 inhibition with AZD1775 abrogates the G2 checkpoint and sensitizes pancreatic cancer cell lines and xenografts to chemoradiation. Additionally, AZD1775 attenuates homologous recombination repair and promotes replication stress in cancer cells. Given our preclinical findings, we designed a phase I dose escalation study of the WEE1 inhibitor AZD1775 with gemcitabine and radiation in patients with unresectable pancreatic cancer (NCT02037230). Methods: The primary objective of our phase I study is to determine the MTD (maximum tolerated dose) of AZD1775 when combined with gemcitabine and radiation in patients with locally advanced pancreatic cancer. Our secondary objectives are to estimate the efficacy of this regimen at the target dose and to determine if WEE1 is inhibited by AZD1775 at or below its target dose in surrogate tissues (hair follicles). Patients with unresectable, non-metastatic pancreatic cancer are eligible for the study. Protocol therapy consists of the administration of AZD1775 and gemcitabine at the assigned dose levels in accordance with a Time-to-Event Continual Reassessment Method. All patients on the study are treated with four cycles of therapy consisting of AZD1775 given orally on days 1, 2 and 8, 9 of a 21 day cycle with gemcitabine given intravenously over 30 minutes on day 1 and day 8. Cycles 2 and 3 are administered with concurrent radiation therapy, 52.5 Gy in 25 fractions to the primary pancreatic tumor. The MTD will be determined by the development of dose limiting toxicities (DLT) within the first 4 cycles of therapy with a target DLT rate of 25%. Blood samples obtained at baseline and after cycles 1, 2, and 4 will be used for correlative studies on circulating tumor cells and tumor derived exosomes. Our estimated accrual is 36 patients. To date we have enrolled 21 patients. Supported by P50 CA130810, R01 CA163895, Cancer Center Core grant P30 CA46592, and the Taubman Institute. Clinical trial information: NCT02037230.
A single arm, prospective multicenter phase II study FOLFIRINOX in patients with advanced and recurrent biliary tract cancer.
Authors: Takahara Naminatsu , Isayama Hiroyuki , Nakai Yousuke , Ioka Tatsuya , Kanai Masashi , Sasaki Takashi , Furuse Junji , Koike Kazuhiko
Published: March 2017

TPS514

Background: The current standard of care for patients with advanced biliary tract cancer (BTC) is gemcitabine and cisplatin (GC) combination chemotherapy. Despite intensive researches, no trials have proved better overall survival (OS) over GC. Recently, FOLFIRINOX provided a remarkable survival benefit over gemcitabine in patients with metastatic pancreatic cancer. Given the promising results of FOLFIRI and FOLFOX in patients with advanced BTC, FOLFIRINOX can be an attractive option in patients with advanced BTC as well. Methods: This is a single-arm, open-label, multi-center phase II study to evaluate the safety and efficacy of FOLFIRINOX in patients with advanced BTC. The major inclusion criteria are as follows; unresectable or recurrent BTC, histologically or cytologically confirmed adenocarcinoma, no prior chemotherapy or radiation therapy, age of 20-75 years, an ECOG PS of 0 or 1, at least one measurable lesion, adequate hematological, liver and renal function. The major exclusion criteria are as follows; UGT genetic polymorphisms of homozygous UGT1A1*6 or *28 or heterozygous UGT1A1*6 and *28, massive pleural effusion or ascites. FOLFIRINOX consists of oxaliplatin of 85 mg/m2, irinotecan of 180 mg/m2, leucovorin of 400 mg/m2 administered by intravenous infusion and fluorouracil of 400 mg/m2 by intravenous bolus and of 2,400 mg/m2 by continuous intravenous infusion every 2 weeks. The primary outcome is progression-free survival (PFS), and the secondary outcomes are OS, tumor response and safety. PFS and OS will be calculated from the date of enrollment until the date of documentation of disease progression or death in patients without disease progression and the date of death. Tumor response will be evaluated according to the RECIST version 1.1 every 2 months. Safety will be evaluated with the CTCAE version 4.0. A total of 35 patients will be required to provide 75% power to detect an increase in median PFS from 6 months provided by standard care of GC to 10 months in patients receiving FOLFIRINOX, with a 24 months of recruitment and 18 months of follow-up. A phase III trial will be considered when this study shows the lower limit of the 80% confidence interval for PFS is longer than 6 months. Clinical trial information: UMIN000020801.
A phase II trial of neoadjuvant chemotherapy with GSL (GEM+TS-1+LV) for marginally resectable pancreatic cancer.
Authors: Sakamoto Yoshihiro , Isayama Hiroyuki , Saito Kei , Arita Junichi , Nakai Yousuke , Hasegawa Kiyoshi , Watadani Takeyuki , Aoki Taku , Koike Kazuhiko , Kokudo Norihiro
Published: March 2017

TPS516

Background: The impact of neoadjuvant chemotherapy (NAC) for borderline resectable pancreatic cancer is under debate. In this context, a phase II trial of neoadjuvant chemotherapy for marginally resectable pancreatic cancer is undergoing since Jan 2014 (UMIN000012480). In this trial, we employed GSL regimen (Gemcitabine 1000mg/m2, TS-1 80mg/m2, LV 50mg) which have reported favorable results (33% of response rate, 93% of disease control rate and 16.6 months of overall survival) for unresectable pancreatic cancer (Cancer Chemother Pharmacol 2014; 74:911). Methods: The subjects were marginally resectable, pathologically proven pancreatic cancer, which consists of borderline resectable because of arterial attachment (BR-A) and locally advanced or unresectable (LA, UR) with short-segment ( = / < 3cm) arterial abutment based on NCCN guideline 2015. At least two surgeons, two medical oncologists, and one radiologist joined a consensus meeting to decide the indication of NAC and evaluated the efficacy of NAC every month. Patients with CR, PR or SD for 2-6 months underwent curative surgery combined with dissection of the nerve plexus around major arteries. The primary endpoint was R0 resectional rate, and the secondary endpoints were resectional rate, response rate, adverse effect, surgical morbidity, mortality, operative time and hospital stay period. Twenty-four patients are going to be enrolled, and 23 patients have undergone enrollment of NAC at the time of submission of the present abstract. Clinical trial information: 000012480.
Clinical utility of quasimonomorphic variation range (QMVR) on the determination of microsatellite instability (MSI) status in Japanese patients (pts) with colorectal cancer (CRC): GI-SCREEN-CRC-MSI sub-study 01.
Authors: Bando Hideaki , Okamoto Wataru , Fukui Takafumi , Yamanaka Takeharu , Akagi Kiwamu , Yoshino Takayuki
Published: March 2017

TPS808

Background: The current analysis for the determination of Microsatellite Instability (MSI) status in tumor requires matched normal DNA as a reference. The Promega MSI panel included five monomorphic markers (NR-21, BAT-26, BAT-25, NR-24, and MONO-27) which were known to have few variant alleles in Caucasian as well as Japanese. Therefore, these markers might be able to determine the MSI status without matched normal DNA, although it is conceivable that Quasi-Monomorphic Variation Range (QMVR) in each ethnic group could be different. In our pilot study, the QMVR in 149 Japanese healthy individuals were 98.4-104.4 base pair (bp) in NR-21, 111.4-117.4 bp in BAT-26, 121.0-127.0 bp in BAT-25, 129.5-135.5 bp in NR-24, and 149.9-155.9 bp in MONO-27, respectively. Methods: This clinical evaluation study is to establish the QMVR in Japanese colorectal cancer (CRC) patients (pts) and to evaluate the clinical utility of the QMVR on the determination of MSI status without matched normal DNA. The primary endpoint is the concordance of MSI status between the standard method using DNA from tumor plus matched normal samples and testing method using DNA from only tumor samples. The new MSI kits including the Promega MSI panel were manufactured under the Quality Management System (QMS) for in vitro diagnostics (IVDs). As the decision algorithm, tumors exhibiting 2 or more markers outside the QMVR were classified as MSI-High, cases with 1 marker outside the QMVR were classified as MSI-Low, and those without any marker outside the QMVRs were classified as microsatellite stable (MSS). Planned enrollment will be 400 pts. Clinical trial information: UMIN000024144.
A randomized phase II study to investigate the deepness of response (DpR) of FOLFOXIRI plus cetuximab (Erbitux) versus FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors: DEEPER.
Authors: Tsuji Akihito , Sunakawa Yu , Ichikawa Wataru , Kubota Yutaro , Kochi Mitsugu , Sekikawa Takashi , Sagawa Tamotsu , Kotaka Masahito , Nakamura Masato , Shimada Ken , Masuishi Toshiki , Satake Hironaga , Yabuno Taichi , Yoshida Taichi , Goto Masahiro , Ota Hirofumi , Okita Yoshihiro , Takeuchi Masahiro , Fujii Masashi , Nakajima Toshifusa
Published: March 2017

TPS818

Background: The FIRE-3 study proved that early tumor shrinkage (ETS) and DpR were superior with FOLFIRI plus cetuximab (cet) compared to bevacizumab (bev) in mCRC patients with RAS wild-type tumors (Stintzing S, et al. Lancet Oncol 2016). A retrospective analysis of treatment groups between FOLFOXIRI plus anti-EGFR antibody and bev showed significantly better DpR and ETS in the anti-EGFR antibody group (48.6% vs. 37.8% for the median DpR; 40.8% vs. 26.4% for the median ETS)(Salvatore L, et al. ESMO 2014). However, there have been few studies comparing cet with bev in combination with the FOLFOXIRI regimen used as a platform. Therefore, it is great interest to investigate whether cet will be more beneficial than bev when combined with the triplet regimen as a promising treatment option. Methods: Key eligibility criteria are as follows: histologically proven unresectable metastatic/recurrent CRC; RAS wild-type tumors; patients who have not received any prior chemotherapies or patients with relapse after at least 12 months following adjuvant chemotherapy. Primary endpoint of this study is the DpR until progression. Key secondary endpoints are the ETS at Week 8, progression-free survival, overall survival, and safety. After randomization, patients receive up to 12 cycles of FOLFOXIRI (irinotecan: 150 mg/m2, oxaliplatin: 85 mg/m2, l-levofolinate: 200 mg/m2, continuous fluorouracil: 2400 mg/m2, every two weeks) plus cet (initial: 400 mg/m2, subsequent: 250 mg/m2, weekly) or bev (5 mg/kg, every two weeks) as induction treatment. Thereafter, fluorouracil, l-levofolinate, and cet or bev are administrated as maintenance treatment. Based on previous reports, the difference of 12.5% in the median DpR between the cet and bev groups was assumed. Each standard deviation was estimated to be 42% (cet group) and 34% (bev group). Under the conditions of significance level of 0.05 for a two-sided test and power of 0.85, the required sample size was calculated to be 360 patients. Thirty-three patients have been enrolled by August 2016. Clinical trial information: 000018217.
Prevention of lymphedema in women with breast cancer (BC): Results of CALGB (Alliance) 70305.
Authors: Paskett Electra D. , Le-Rademacher Jennifer , Oliveri Jill , Liu Heshan , Seisler Drew K. , Sloan Jeffrey , Armer Jane M. , Naughton Michelle Joy , Hock Karen , Schwartz Michael A. , Unzeitig Gary Walter , Padula Gilbert D. A. , Grubbs Stephen S. , Yee Lisa , Bailey Lisa , Willey Shawna C. , Sunnenberg Thomas Dean , Baddi Lisa L. , Fleming Gini F. ,   CALGB 70305 Investigators
Published: March 2017

104

Background: Lymphedema (LE), a side effect of BC treatment, affects 8%–56% of women. The study tested the effectiveness of an education only vs education + exercise intervention on LE incidence in a group randomized trial (NCT00376597) of 38 cooperative group sites. Methods: Newly diagnosed women with stage I-III BC were consented and arm circumference and range of motion were measured pre-surgery. After surgery, patients (pts) were enrolled based on the randomization assignment of their treating institution, stratified by their type of node dissection (sentinel or axillary), and received either: education only: its causes, signs, symptoms and risk reduction strategies, or education + personalized exercise instruction from a physical therapist, with elastic compression garments to wear during heavy arm use and air travel. Pts completed surveys and arm measurements at baseline (BL), 12 and 18 months with the LE endpoint defined as ≥ 10% difference in limb volume at any time from BL to 18 months or physician diagnosis of LE. Cochran-Mantel-Haenszel (CMH) tests were used to compare the LE-free rate between arms, adjusted for type of biopsy. Logistic regression assessed predictors of LE. Results: 568 pts were enrolled, 45% in education only, and 55% in education + exercise, with 554 (98%) included in the analyses. Pts were on average 57.7 years, White (83%), non-Hispanic (92%) and married (62%). 47% only had sentinel node dissection, 35% had mastectomy, and 37% had chemotherapy. The LE-free rate was 58% in education only vs 55% in education + exercise (CMH p = 0.73). Predictors of LE included surgery type (lumpectomy vs mastectomy, OR = 2.22, p < 0.001) and chemotherapy (no vs yes, OR = 1.73, p = 0.02), after adjusting for BMI and type of node dissection. Only one-third wore the sleeve at least 75% of the time and only 50% did LE exercises at least weekly. Conclusions: There was no difference by intervention arm in LE incidence by 18 months. Poor adherence in the education + exercise arm may have been a factor. Additional analyses will assess quality of life, body image and knowledge about LE by arm. Further research is needed to effectively prevent LE in pts after BC surgery. Research Support: UL1TR001409; U10CA037447, UG1CA189823 Clinical trial information: NCT00376597.
Fertility preservation and decisional regret in young breast cancer survivors: A longitudinal analysis.
Authors: Dewald Samantha Rose , Natarajan Loki , Su Irene
Published: March 2017

106

Background: Fertility is important to many young breast cancer survivors (YBCS), who face difficult decisions on whether to undergo fertility preservation prior to treatment. Because few longitudinal data assessing decisional regret are available, the objectives of this study were to assess longitudinal changes in decisional regret on fertility preservation following breast cancer diagnosis; determine if fertility preservation treatment decisions are related to decreased decisional regret. Methods: From 3 academic breast cancer programs, 169 YBCS younger than age 45 were recruited at diagnosis between 2009 and 2012 and followed prospectively for ovarian function. Participants completed questionnaires on fertility preservation choices and the Decisional Regret Scale (DRS) during study visits every 6 months for up to 5 years. DRS is scored 0 (no regret) to 100 (highest regret). DRS was dichotomized as none versus any decisional regret. Generalized linear models estimated the change in DRS over time and the association between patient characteristics and DRS. Results: Mean age at diagnosis was 38.7 (SD 4.8). Median total follow-up was 176 days (IQR 84 to 1415 days). Enrollment DRS was available for 89 women; 48% reported decisional regret about fertility preservation (median DRS=20). Participants worried about future fertility were more likely to report decisional regret (p=0.009). 31% underwent fertility preservation, but this was not associated with decisional regret (p=0.65). In repeated measures analysis for the entire cohort, no significant change in DRS occurred over this time period (OR 0.8, 95% CI 0.4-1.7). Worry about future fertility remained significantly associated with DRS over time (OR 55.1, 95% CI 7.7-395.1). Conclusions: In a cohort of YBCS, experiencing decisional regret about fertility preservation persists for years after diagnosis. Those worried about future fertility are more likely to experience decisional regret regarding fertility preservation.
Challenges in accessing reproductive health care in young cancer survivors.
Authors: Thom Bridgette , Benedict Catherine , Friedman Danielle Novetsky , Diotallevi Debbie , Raghunathan Nirupa Jaya , Pottenger Elaine , Kelvin Joanne Frankel
Published: March 2017

107

Background: Infertility and early menopause are well-established late and long-term effects of many cancer treatments. Fertility preservation (FP) before (and in some cases after) treatment allows many survivors to achieve their family building goals despite gonadotoxic treatment. FP, however, is costly, and there is inconsistent, incomplete, or absent coverage across insurances. Furthermore, as many young survivors are un- or underinsured, disparities in referrals and service utilization have emerged. This presentation provides an overview of reproductive health care-related financial issues affecting young adult survivors, including cost of care, access to services, and relevant advocacy efforts, and highlights an analysis of the impact of income on FP decisions in a national sample of female survivors. Methods: We recruited female survivors aged 18-35 via social media and collected data using a web-based survey. Analyses included bivariate statistics and multiple logistic regression. Outcomes were receiving a fertility intervention (undergoing evaluation and/or fertility preservation of any sort) and freezing eggs/embryos before or after treatment. Results: 346 survivors, who were an average of 4.9 years (sd = 5.4) post-treatment, participated. 296 (86%) reported income: 35% <$50K; 39% $50K-100K; and 26% over 100K. Of 259 respondents who did not undergo FP, 27% reported cost as a barrier. In logistic regression, income was significantly related with receiving an intervention and freezing eggs/embryos. Controlling for age and nulliparity, high-income survivors were more likely to receive a fertility intervention (OR = 3.0, 95% CI: 1.3, 6.9) and to freeze eggs/embryos (OR = 3.4, 95% CI: 1.2, 9.5) than low-income survivors. Conclusions: Our findings of disparity in utilization of reproductive health care among cancer survivors were similar to the published literature, with income impacting respondents’ receipt of fertility intervention and freezing of eggs/embryos. Clinical interventions and policy initiatives must address this service gap. Health care providers can help ensure that cancer survivors have access to available financial resources to assist with cost to facilitate their reproductive health care.
Late effects among young thyroid cancer survivors.
Authors: Blackburn Brenna , Ganz Patricia A. , Rowe Kerry G. , Wan Yuan , Deshmukh Vikrant , Newman Michael , Fraser Alison M , Smith Ken R , Kim Jaewhan , Kirchhoff Anne C. , Poruznik Christina , Hanson Heidi , Monroe Marcus , Hashibe Mia
Published: March 2017

111

Background: Thyroid cancer is the most rapidly increasing cancer with over 600,000 thyroid cancer survivors in the U.S. Thyroid cancer affects a young population and the 5-year survival rate is over 98%. There have been few studies on the late effects of thyroid cancer, especially in younger populations. The aim of this study was to examine if thyroid cancer survivors diagnosed < 40 years experience greater risks of late effects than older age groups for diseases associated with aging. Methods: Up to 5 cancer free individuals were matched to each thyroid cancer survivor based on birth year, sex, birth state, and follow up time from case diagnosis date, within the Utah Population Database. Electronic medical records, statewide ambulatory surgery and inpatient discharge data were used to identify late effects stratified over three time periods: 1-5, 5-10, and > 10 years after cancer diagnosis. Cox proportional hazards models were used to estimate hazard ratios (HR) with adjustment on matching factors, race, BMI at diagnosis, and Charlson Comorbidity Index at diagnosis. Results: There were 4,060 thyroid cancer survivors and 18,557 matched cancer free individuals (1,407 cases diagnosed ages < 40 years, 2,076 cases diagnosed ages 40-65 years). The risk for hypertension was significantly increased in both younger (HR = 1.54, 95%CI = 1.18, 2.01) and older patients (HR = 1.30, 95%CI = 1.11, 1.53) > 10 years after cancer diagnosis. For heart disease, increased risks persisted for the young patients > 10 years after cancer diagnosis for heart valve disorders (HR = 2.43, 95%CI = 1.36, 4.33) and for peri-, endo- or myocarditis (HR = 5.12, 95%CI = 1.04, 25.14), while corresponding HRs for the older age group did not suggest increased risks. For osteoporosis, the younger patients had a higher risk (HR = 8.77, 95%CI = 3.18, 24.18) than the older population (HR = 2.55, 95%CI = 2.07, 3.13) 1-5 years after cancer diagnosis. Conclusions: Thyroid cancer survivors diagnosed at < 40 years had increased risks for diseases associated with aging such as hypertension, heart disease, and osteoporosis. As thyroid cancer affects a young population, understanding what late effects may result from the treatment can lead to better surveillance and disease management.
Racial disparities in breast cancer mortality among women with diabetes mellitus.
Authors: Gegechkori Nana , Pak Pamela , Wisnivesky Juan P. , Lin Jenny J
Published: March 2017

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Background: Multiple reasons have been cited for racial disparities in breast cancer survival, including differences in screening, tumor biology, estrogen receptor status, stage at presentation, treatment and comorbidities. Recent studies suggest that minority women are more likely to have diabetes and diabetes has been shown to increase breast cancer risk and worsen cancer prognosis. We sought to evaluate whether there is disparity in breast cancer mortality among breast cancer survivors with comorbid diabetes. Methods: We identified women >65 years diagnosed with primary breast cancer between 2007 and 2010 from the SEER-Medicare database and followed them for 36 months after cancer diagnoses. Our primary outcome was breast cancer mortality. We excluded patients for whom diagnoses were obtained from death certificates or at autopsy, with incomplete data with regards to the stage at diagnosis and those without Part B coverage. The association between race and breast cancer mortality was assessed using a multivariable Cox regression with competing risk analysis. Results: A total of 9,545 breast cancer survivors with pre-existing diabetes were included in the analysis. Black women were more likely to be diagnosed at later stage and to be younger (p<0.001). There were no differences in cancer treatment by race. After a median follow-up of 36 months, 68.9% of black vs. 73.9% of white patients were still alive (p< .0001). After censoring women who died from other causes and adjusting for age, year of diagnosis, stage, cancer treatment (surgery, chemotherapy and/or radiation) and Charlson comorbidity score, black race remained associated with increased breast cancer mortality (Hazard Ratio 1.45 (95% CI, 1.20-1.73). Conclusions: Even after controlling for cancer-related treatment factors, black breast cancer survivors with diabetes have significantly worse breast cancer survival. Further research should investigate how to improve care for minority women who are at higher risk for breast cancer mortality.
Sinoatrial node dysfunction after stereotactic ablative radiation therapy in the chest.
Authors: Qian Yushen , Dudley Sara Aileen , Kumar Kiran , Chaudhuri Aadel , Chin Alexander , Harris Jeremy Phillip , Prionas Nicolas , Nwachukwu Chika , Bagshaw Hilary , Pollom Erqi L. , Durkee Ben , Shultz David Benjamin , Gensheimer Michael F. , Diehn Maximilian , Loo Billy W.
Published: March 2017

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Background: Sinoatrial node (SAN) injury following stereotactic ablative radiation therapy (SABR) in the chest has not been reported in the literature. We report SAN dysfunction as a potential toxicity of SABR in the chest. Methods: We examined the clinical courses and SABR plans of 47 patients treated for T1 or T2 non-small cell lung cancer of the right upper lobe, middle lobe, lower lobe, or hilum. After developing a contouring atlas for the SAN, based upon the junction between the superior vena cava and the right atrium, dose to the SAN was retrospectively determined for each patient. We identified 13 patients whose treatment imparted significant dose to the SAN, as defined by the SAN encompassed within the 10% prescription isodose (IDL) line. Biologically effective doses (BED), acute and chronic, were correlated with SAN toxicity. Results: Patients underwent SABR to the right lung to a dose of 40-50 Gy in 4 or 5 fractions, with mean acute BED (alpha/beta ratio = 10) of 100.2 Gy and late BED (alpha/beta ratio = 3) of 222.7 Gy. Mean volume of the GTV and PTV were 26.1 and 75.1 mL, respectively. Mean follow-up was 25.5 months. The mean volume of the SAN was 0.37 mL. Average max dose and mean dose to the SAN were 24.7 and 70.7 Gy, respectively. Of the 13 patients whose treatment imparted significant dose to the SAN, one patient without prior arrhythmia developed symptomatic SAN dysfunction requiring pacemaker placement at 6 months after completion of treatment. The sinoatrial node of the patient received a maximum dose of 44.8 Gy in 4 fractions, correlated with an acute BED (alpha/beta ratio = 10) of 90 Gy and late BED (alpha/beta ratio = 3) of 194.1 Gy, and a mean dose of 35.5 Gy in 4 fractions, correlated with an acute BED (alpha/beta ratio = 10) of 71 Gy and late BED (alpha/beta ratio = 3) of 153.8 Gy. This was the third highest max dose and second highest mean dose to SAN in the cohort. Conclusions: We report sinoatrial node dysfunction as a potential toxicity of SABR in the chest for non-small cell lung cancer. Caution is advised when treatment imparts significant dose to the sinoatrial node.
Development of a senior oncology clinic for geriatric cancer patients.
Authors: Sangermano Sarah , Caprio Anthony James , Cormier Shannon , Cooper Markecia
Published: March 2017

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Background: By 2030, more than 70% of all new cancer diagnoses will affect patients older than 65. The National Comprehensive Cancer Network recommends performing a Comprehensive Geriatric Assessment for elderly patients with cancer. Levine Cancer Institute (LCI) has developed a Senior Oncology Clinic to address the unique needs of geriatric oncology patients. Methods: Prior to the clinic visit, the patient completes a standardized questionnaire. During the visit, the patient is evaluated by a pharmacist, physical or occupational therapist, geriatrician and oncologist. The pharmacist reviews the vaccination history, prescription and non-prescription medications, and supplements. The therapist assesses balance, strength, and fatigue. The geriatrician assesses cognition, medical comorbidities, and geriatric syndromes. The oncologist screens for depression, and reviews oncologic treatment options. Final recommendations are sent by the team to the referring provider and primary care physician. Results: The Senior Oncology Clinic at LCI saw 31 survivors in 2015, and has seen 24 survivors in 2016. Patients receive referrals to a variety of services such as outpatient therapy, nutrition services, and social work. Recommendations are shared with referring providers to address common conditions in older adults as well as cancer-specific treatment recommendations. Due to the success of the program, the clinic has recently been expanded to a second site, LCI-Albemarle. This site utilizes a telemedicine model to provide the clinic at a rural location. Challenges to the program’s effectiveness include provider scheduling, clinic space, data management, and administrative management. A Program Coordinator was recently hired to oversee these aspects of the clinic. Patient challenges include transportation, medical complexity of the population, and missed appointments. Conclusions: A Senior Oncology Clinic is an effective way to perform a multidisciplinary assessment to guide cancer treatment in the geriatric population. These assessments can improve treatment decisions, detect geriatric syndromes, and recommend interventions to help improve the quality of life.
Ongoing needs in 625 women living beyond early breast cancer.
Authors: Capelan Marta , Battisti Nicolo Matteo Luca , McLoughlin Anne , Snuggs Nikki , Maidens Vivienne , Slyk Patrycia , Peckitt Clare , Stanway Susannah Jane , Doyle Natalie , Wiseman Theresa , Ring Alistair E.
Published: March 2017

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Background: In some healthcare systems people with a diagnosis of early invasive breast cancer (BC) are discharged from hospital-based follow-up after completion of initial treatment. However there are limited data on the prevalence of specific ongoing physical and psychological needs in such people. Methods: We conducted a retrospective study involving survivors of BC who entered into the Open Access Follow-Up (OAFU) program at The Royal Marsden Hospital (UK) from January to December 2015. The ongoing needs were assessed using the Holistic Needs Assessment (HNA) (a checklist questionnaire regarding physical, emotional, family, practical and spiritual needs) or extracted directly from the Electronic Patient Record (EPR). Results: Six hundred and twenty-five invasive survivors of BC were seen for the first time in the OAFU program after completing their initial treatment. Ongoing needs were identified in 214 (34%) from their returned HNA and in 411 (66%) direct from EPR. Demographic and treatment characteristics were not significantly different between the two groups. The median age was 59 year-old. Median time from diagnosis to assessment was 8.9 months. Ongoing needs were categorized in 3 different groups: 0, 1-4 and ≥ 5 needs. 513 (82%) survivors of BC had 0-4 ongoing needs and 18% had ≥ 5 needs. Physical and emotional needs were the most frequently reported (55% and 24% respectively). Rates of ongoing needs were more frequently identified using formal HNA assessment than extraction from EPR: overall physical needs: 79% vs. 43% (p < 0.001) and emotional needs 50% vs. 10% (p < 0.001). The most frequent specific ongoing needs were: hot flushes (23%), fatigue (21%), pain (19%), worry, fear and anxiety (16%), sleep problems (14%), tingling in hands/feet (11%), dry, itchy or sore skin (11%) sadness and depression (10%), changes in weight (10%) and memory or concentration problems (10%). Conclusions: Fifty-five percent survivors of BC reported at least one physical need and 24% an emotional need. Consistently higher levels of ongoing needs were identified using the HNA formalized checklist. The HNA enables people self-reflection and promotes discussion with the health professional in order to identify ongoing needs and provide on-going supportive care.
Risk assessment for lymphedema in breast cancer survivors.
Authors: Lyman Martha Bonney , Truax Marita Ferro
Published: March 2017

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Background: Breast cancer patients are receiving survivorship care plans that describe potential late effects of treatment. The potential for lymphedema ranges from 5% to 53% and is a serious long term problem. In the past, water displacement was the “gold standard” for measuring lymphedema; this involves placing the arm into a large graduated cylinder filled with water to measure displacement compared with the opposite arm. This method is inconvenient for both patient and practitioner and can cause significant anxiety. Methods: In 2010 we began assessing women undergoing unilateral axillary surgery for preclinical and clinical lymphedema using a method that measures bioimpedance, using the L-Dex U400 analyzer. L-Dex uses a mild electrical current to assess fluid levels in the extracellular compartment, earlier than a patient might feel a change in size or weight. One hundred thirty -seven patients were assessed using both volume displacement and L-Dex preoperatively, as a baseline and repeating at 3 to 6 month intervals for three years. Results: Of the patients followed, 83% had sentinel node excision only and 17% had completion axillary dissection. Our study identified an overall lymphedema rate of 7%. Of the patients with full axillary dissection the lymphedema rate was 9% and those with sentinel node excision were found to have no clinical lymphedema (0%). In every case where the patients developed lymphedema the L-Dex bioimpedance measurement identified a change 100% of the time before fluid volume displacement became out of range. Conclusions: Based on our results and the ease of use of the bioimpedance analysis, we have added lymphedema assessment using the L-Dex analyzer to our survivorship process. Patients with invasive cancer undergoing unilateral axillary node surgery are assessed at the same time they receive their sentinel node tracer injection. If there is a sentinel node excision only they are checked once or with any symptom. Patients who have a complete axillary dissection are to be followed for three years. This modest intervention should reduce anxiety surrounding one of the most serious late effects of breast cancer.