bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved local relapse-free and overall survival with secondary surgery after a first R1 or R2 resection in soft tissue sarcoma (STS) of the limbs or trunk wall: An analysis 10,931 patients (pts) in NETSARC.
Authors: Gouin Francois , Stoeckle Eberhard , Bonvalot Sylvie , Honoré Charles , Decanter Gauthier , Anract Philippe , Bompas Emmanuelle , Ferron Gwenael , Sirveaux Francois , Rochwerger Richard , Carrere Sebastien , DiMarco Antonio , Ropars Mikael , Le Nail Loic-Romée , Marco Oren , Guiramand Jerome , Italiano Antoine , Le Cesne Axel , Penel Nicolas , Blay Jean-Yves ,   French Sarcoma Group - Group Etude Tumeur Osseuses FSG-GETO
Published: March 2020

11056

Background: We previously reported that secondary resection (2Surg) improved local relapse free (LRFS) but not overall survival (OS) in a retrospective series of pts with localized STS after unplanned 1st excision. Here we investigated the impact of 2Surg specifically after a first R1 or R2 resection in the 10931 pts with STS of the limb or trunk wall included in the nationwide NETSARC database from 2010 to 2017. Methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDT), funded by the French NCI (INCa). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma pts. Statistics were performed with SPSS23.0. LRFS, metastasis-free survival (MFS), OS compared with the logrank test. Results: The series included 5598 (51.2%) males. Median age was 56.7. Tumor sites: 5295 (49.4%) lower limb, 3670 (33.6%) trunk wall. 1966 (18.0%) upper limb. As previously reported in the entire series, local RFS (LRFS) and RFS (p<0.001), but not OS, were superior for pts presented to a NETSARC MDT (NMDT), or operated in a NETSARC center (N=4417, 41%). LRFS & OS were best for pts presented to a NMDT AND operated in NETSARC centers; while the worst LRFS & OS were observed in pts presented in a NMDT but not operated there (p<0.001). Among the 2081 pts with a first R1 resection in whom 2Surg was documented, 1047 (50.3%) were reoperated. R1 reoperated pts had a superior LRFS, metastatic free survival (MFS) and OS (p<0.001). LRFS (p<0.001), MFS (p=0.05) and OS (p<0.001) were superior after 2Surg only in pts operated 1st outside a Netsarc center. There were 823 pts with a first surgery with R2 resection in whom 2Surg was documented: 619 (75.2%) were reoperated. R2 reoperated patients had a superior LRFS and OS (p=0.01). MFS was not different. LRFS (p<0.001) & OS (p<0.001) were superior after 2Surg only in pts operated 1st outside a Netsarc center. 2028 (%) pts had 2Surg. Pts for whom 2Surg was in a NetSARC center had a superior LRFS (p<0.001) and OS (p=0.01) when operated first outside a NETSARC center. Conclusions: In this nationwide series of limb or trunk wall STS, 2Surg after a R1 or R2 primary excision improves LRFS & OS when the pts were operated 1st outside a reference center. 2Surg in a NETSARC center was associated with a better LRFS and OS.
A phase I/II investigation of nivolumab and ABI-009 (nab-sirolimus) in advanced undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), chondrosarcoma (CS), osteosarcoma (OS), and Ewing sarcoma: Preliminary efficacy and safety results.
Authors: Gordon Erlinda Maria , Chua-Alcala Victoria S. , Kim Katherine , Baby Rekha , Angel Nicole , Quon Doris , Wong Steven , Chawla Sant P.
Published: March 2020

11057

Background: Immune checkpoint inhibitors that promote sustained T cell activation may have synergistic activity with an mTOR inhibitor. This phase 1/2 study is aimed to investigate if ABI-009 a novel albumin-bound mTOR inhibitor is feasible and improve clinical outcomes in combination with nivolumab. Methods: Eligible patients with advanced UPS, LPS, CS, OS, or Ewing sarcoma are treated with the standard dose of nivolumab (240 mg given IV every 3 weeks, Day 1 of every 21-day Cycle). ABI-009 will be given IV on Days 8 and 15 of each cycle starting on Cycle 2 following the 2nd nivolumab dose. Phase 1 portion is a dose-finding study using the 3+3 design. The starting dose of ABI-009 is 56 mg/m2, and sequentially escalating doses are 75 and 100 mg/m2. The primary endpoint is to identify the maximum-tolerated dose (MTD) of ABI-009 + nivolumab, secondary endpoints include disease control rate, progression-free survival (PFS), and overall survival (OS). Exploratory endpoints include correlation of PFS and OS with PD-L1 and other biomarkers. The Phase 2 part of study will enroll 31 additional patients to further assess efficacy and safety at the MTD. Results: 9 patients were treated in Phase 1 (n = 3 each dose level); 5/9 patients had OS, 3/9 CS, and 1 had Ewing sarcoma. No dose-limiting toxicities (DLTs) were observed, the MTD was not reached, and 100 mg/m2 ABI-009 was designated as the recommended phase 2 dose. Safety analysis: At Dose 1: Grade 3 treatment-related adverse events (TRAEs) included hyper dyslipidemia (n = 1), and hyperglycemia (n = 1). At Dose 2: Grade 3 TRAEs included increased ALT (n = 1). At Dose 3: Grade 3 TRAEs included hypophosphatemia (n = 1). Seven of 9 patients have discontinued treatment: 5 patients due to PD, 2 with SD opted to stop treatment due to drug-related Grade 2 AEs (pruritus, acneiform rash, and 2 with SD are still on therapy at Dose 3. The median PFS at dose level 3 has not yet been reached. Conclusions: The MTD was not reached and Dose 3 (100 mg/m2) has been designated as the phase 2 dose of ABI- 009, combinable with nivolumab. Enrollment to phase 2 is ongoing. Clinical trial information: NCT03190174.
Activity of hormonal treatment in uterine smooth muscle tumors of uncertain malignant potential (STUMP): A mono-institutional referral center experience in advanced disease.
Authors: Sanfilippo Roberta , Sbaraglia Marta , Fumagalli Elena , Baldi Giacomo Giulio , Fucà Giovanni , Morosi Carlo , Barisella Marta , Dei Tos Angelo Paolo , Casali Paolo Giovanni
Published: March 2020

11066

Background: STUMP ecompass a group of uterine mesenchymal neoplasms in which the clinical behavior cannot be predicted on morphological grounds. A malignant clinical evolution is seen in approximately 10-20% of cases. When STUMP relapse, the label of “low-grade leiomyosarcoma” is sometimes found to be appropriate, though current histopathological criteria for uterine leiomyosarcoma (so called “Stanford criteria”) would exclude even the existence of low-grade uterine smooth muscle neoplasms. As they express ER and PR, hormonal treatment with GnRH inhibitors or aromatase inhibitors (AIs) may represent a therapeutic option. Methods: From October 2015, we have been treating with hormonal therapy relapsing patients with an initial diagnosis of STUMP, whose pathological aspect on retrospect was consistent with a “low-grade uterine leiomyosarcoma”. We identified 8 patients. Pathological diagnosis was centrally reviewed by expert sarcoma pathologists. Results: Eight pts were treated: 7 in first line; 1 pt in 4th line, following failure of chemotherapy (gemcitabine and taxotere, adriamycin and dacarbazine, trabectedin). Two premenopauseal pts were treated with GnRH inhibitors, 2 with a combination of GnRh inhibitors and an aromatase inhibitor, 3 with aromatase inhibitors only and 1 with selective progesterone-receptor modulator. 7 patients are evaluable for response and all of them had a partial response as best response. Median progression-free survival was 31 months. Conclusions: In our series, all patients with a centrally reviewed diagnosis retrospectively consistent with a “low grade uterine leiomyosarcoma” responded to hormonal treatment. Therefore, these pts may make up a subgroup with therapeutic and prognostic relevance. “Stanford criteria” need to be re-assessed, in an effort to improve prognostic and therapeutic stratification of uterine smooth muscle neoplasms, possibly shrinking the scope of currently defined STUMP.
Osteonecrosis of the jaw in patients with cancer receiving zoledronic acid for bone metastases: SWOG S0702, NCT00874211.
Authors: Van Poznak Catherine H. , Unger Joseph M. , Darke Amy K. , Moinpour Carol , Bagramian Robert A. , Schubert Mark M. , Hansen Lisa Kathryn , Floyd Justin D. , Dakhil Shaker R. , Lew Danika L. , Wade James Lloyd , Fisch Michael Jordan , Henry Norah Lynn , Hershman Dawn L. , Gralow Julie
Published: March 2020

11502

Background: Osteonecrosis of the jaw (ONJ) may occur in cancer patients (pts) with metastatic bone disease (MBD) treated with bone modifying agents. No large prospective studies have precisely determined the incidence of ONJ. A better understanding of the true incidence and predictors of ONJ is needed. Methods: SWOG S0702 was a prospective observational study that assessed the cumulative incidence (CI) of ONJ at 3 years in pts with MBD from any malignancy receiving zoledronic acid (Zol). Participants must have had either limited or no prior exposure to bone modifying agents and a clinical care plan that included use of Zol within 30 days of registration. Cancer treatments, bone modifying agents (including Zol), and dental care were administered as clinically indicated and were not directed by S0702. Baseline and every 6 m followup dental exams were recommended. Report forms (medical, dental and pt reported outcomes) were submitted every 6 m but if ONJ was diagnosed, follow up interval became every 3 m. Protocol defined ONJ required exposed bone in the maxillofacial region present 8 weeks or more in a pt who was receiving or had been exposed to a bisphosphonate, and had not had radiation therapy to the craniofacial region. Results: The study enrolled 3,491 evaluable pts (breast 1,120; myeloma 580; prostate 702, lung 666, other 423) between 2009-2013. About 2/3 of pts had a baseline dental exam. Overall, 87 pts had confirmed ONJ. The cumulative incidence of ONJ was 0.8% at year 1 (95% CI: 0.5%-1.1%), 2.0% at year 2 (95% CI: 1.5%-2.5%), and 2.8% at year 3 (95% CI: 2.3-3.5%). Rates of 3-year confirmed ONJ were highest in myeloma pts (4.3%; 95% CI, 2.8%-6.4%). Pts with planned Zol dosing intervals of every 3-4 weeks (n = 3,032, 87.2%) were much more likely to experience ONJ than pts with planned dosing intervals of 5 weeks or greater (n = 447, 12.8%; 3.2% vs 0.7%; HR = 4.80, 95% CI, 1.52-15.18, p = .008). Fewer total number of teeth, the presence of dentures and any oral surgery at baseline were all associated with a higher rate of ONJ. Conclusions: About 1 in 40 patients receiving Zol for MBD developed ONJ. S0702 provides information to guide stratification of risk for developing ONJ in pts with MBD receiving Zol. Cancer type, oral health and frequency of Zol dosing affect risk of ONJ. Clinical trial information: NCT00874211.
Olanzapine (OLN) versus aprepitant (APR) in patients receiving high-emetogenic chemotherapy: Final results of randomized phase II trial.
Authors: Rumyantsev Alexey , Glazkova Elena , Nasyrova Rukhshona , Ignatova Ekaterina , Chitia Lia , Popova Anna , Chekini Dzhennet , Kochetkova Yaroslava , Kit Sergei , Elsnukaeva Kheda , Menshikova Sophia , Sekhina Olga , Pokataev Ilya , Tyulyandina Alexandra , Stenina Marina , Frolova Mona A. , Bulanov Anatoly , Fedyanin Mikhail , Tryakin Alexey , Tjulandin Sergei
Published: March 2020

11504

Background: Management of chemotherapy-induced nausea and vomiting (CINV) remains challenging. OLN might provide several benefits over APR which is current standard of care – particularly in terms of nausea control and cost effectiveness. However, sedation associated with recommended doses of olanzapine precludes its wide use in oncology practice. Methods: This was randomized phase II single center study aimed to compare OLN and APR in CINV prophylaxis. Key inclusion criteria were: chemo- and radio-therapy naïve patients, planned administration of high-emetogenic chemotherapy (cisplatin, carboplatin AUC≥4, doxorubicin etc). Patients were randomized 1:1 ratio in the following arms: olanzapine 5 QD day 0-4 or aprepitant 125 mg day 1, 80 mg day 2,3. All patients received ondansetron 16 mg day 1 and dexamethasone 8 mg day 1-3. Primary endpoint was complete nausea control (no nausea and no rescue medication) 0-120 hours after chemotherapy. Complete response (no emesis and no rescue medication) was a key secondary end point. Nausea was assessed using MASCC Antiemesis Tool. Sample size: 94 patients to increase nausea control rate from 40 to 70% (α = 0.05; β = 0.80; 10% of estimated data loss). Results: We included in the analysis 93 patients who could be evaluated. The groups were well balanced, median age was 49 years, vast majority of patients (95.6%) were females. The proportion of patients with complete nausea control in OLN and APR groups was 44.2% and 24.0% respectively (RR 2.5; 95% CI 1.04-6.08; p = 0.039). Complete response was achieved in 74.4% and 54.0% patients respectively (RR 2.48; 95% CI 1.026-5.99; p = 0.041). No differences in rates of undesired sedations were detected. Conclusions: Our data suggests superiority of OLN regimen in terms of nausea control. This regimen deserves further investigation. Clinical trial information: NCT03478605.
Safety of pregnancy following breast cancer (BC) in patients (pts) carrying a BRCA mutation (mBRCA): Results of an international cohort study.
Authors: Lambertini Matteo , Ameye Lieveke , Hamy Anne-Sophie , Zingarello Anna , Poorvu Philip Daniel , Carrasco Estela , Grinshpun Albert , Han Sileny , Rousset-Jablonski Christine , Ferrari Alberta , Paluch-Shimon Shani , Cortesi Laura , Senechal Claire , Miolo Gianmaria , Pogoda Katarzyna , Perez-Fidalgo Jose Alejandro , De Marchis Laura , Del Mastro Lucia , Peccatori Fedro , Azim Hatem A.
Published: March 2020

11506

Background: Very limited data are available on the safety of pregnancy and reproductive outcomes in mBRCA pts with prior BC history. We report the results of the largest study to date addressing these questions. Methods: This international, multicenter, hospital-based, retrospective cohort study included consecutive pts with invasive early BC (stage I-III) diagnosed between Jan-2000 and Dec-2012 at the age of ≤40 years and carrying a deleterious germline mBRCA. Primary endpoints were pregnancy rate and disease-free survival (DFS); overall survival (OS) and pregnancy outcomes were secondary endpoints. To account for guarantee-time bias, we performed two survival analyses: 1) Case-control approach matching pregnant and non-pregnant (1:3) pts for classic prognostic factors (each non-pregnant control had a disease-free interval ≥ than the time elapsing between BC diagnosis and date of pregnancy of the matched pregnant case); 2) Extended Cox model with time-varying covariates including all pts. Results: 1,252 mBRCA BC pts (811 mBRCA1, 430 mBRCA2, 11 mBRCA1&2) were included from 30 centers worldwide, of whom 195 pts had a pregnancy (pregnancy rate = 16% [95% CI 14-18]) after a median 4.5 years (range 3.1-6.7 years) following BC diagnosis. Pregnant pts were younger and had more ER-negative tumors (all p < 0.01). 16 (8.2%) and 20 (10.3%) pts had an induced and spontaneous abortion, respectively. Among the 150 (76.9%) pts who conceived (n = 170 babies), pregnancy complications and congenital anomalies were described in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up was 8.3 years (range 8.1-8.7 years). In the case-control analysis, pregnant pts had better DFS (HR 0.71; 95% CI 0.51-0.99; p = 0.045), with no difference in OS (HR 0.86; 95% CI 0.44-1.67; p = 0.65). Subgroup analysis suggested that the superior outcome was restricted to mBRCA1 pregnant pts (p-interaction < 0.01). Similar results were obtained in the second supportive analysis. Conclusions: Pregnancy following BC is safe in mBRCA pts, particularly mBRCA1, with no detrimental impact on maternal prognosis or fetal outcomes . These findings are of paramount importance for fertility counseling in young mBRCA BC pts.
Cognitive rehabilitation program to improve cognition of cancer patients treated with chemotherapy: A randomized controlled multicenter trial.
Authors: Dos Santos Mélanie , Rigal Olivier , Léger Isabelle , Licaj Idlir , Dauchy Sarah , Levy Christelle , Noal Sabine , Segura Carine , Delcambre Corinne , Allouache Djelila , Parzy Aurélie , Lange Marie , Capel Aurélie , Grellard Jean-Michel , Clarisse Bénédicte , Lefel Johan , Joly Florence
Published: March 2020

11521

Background: Cognitive impairment induced by cancer chemotherapy (CT) has been identified as an important side-effect with negative impact on quality of life (QoL) without specific treatment. We evaluated the impact of computer-assisted cognitive rehabilitation (CR) on cognitive complaint, objective cognitive dysfunction and QoL among cancer patients treated with CT. Methods: We included cancer patients with cognitive complaint occurring during CT or within 5 years of the end of CT. Patients were randomly assigned in a 1:1:1 ratio to face-to-face CR with a neuropsychologist (group A), home cognitive exercises (group B) or phone follow-up (group C) with 9 sessions over 3 months. Cognition was assessed by the Functional Assessment of Cancer Therapy Cognitive Function (FACT-Cog) completed by a neuropsychological battery of test and QoL assessment by the FACT-General (FACT-G). The primary endpoint was the proportion of patients with 7-point improvement in the perceived cognitive impairments (PCI) of the FACT-Cog between baseline (T0) and the end of the program (T3). Results: 167 patients were enrolled, median age was 50 years [43-59] and 96% were women with mainly breast cancer. Compliance rate with completion of all sessions was 76, 61 and 75% respectively. Proportion of patients with 7-point PCI improvement were 73, 55 and 56% without reaching the statistically significant difference between group A and B (p = 0.07) and group A and C (p = 0.08). The mean difference in PCI score were 17, 10 and 10 (p = 0.03). Patients with CR improved their working memory with significant difference between group A and C (1.4 versus 0.3, p < 0.001) but not between group A and B (1.4 versus 1.1, p = 0.43). There was a significant impact of CR on the FACT-Cog subscale score of QoL (p = 0.01) in favor of the group A, but not on the different dimensions of the FACT-G. Patients in group A presented improvement in depression compared to group B and C: -6.5 versus -1.7 and -2.3 (p = 0.03). Conclusions: CR with a neuropsychologist improves cognitive complaint. Cognitive stimulation showed improvements in working memory. CR was associated with better QoL linked to cognitive disorders and lower levels of depression. Clinical trial information: NCT01788618.
Prognostic understanding in hematologic malignancies: A multicenter longitudinal study.
Authors: Loh Kah Poh , LeBlanc Thomas William , Lee Stephanie , Back Anthony , Duberstein Paul , Mohile Supriya Gupta , Epstein Ronald M. , El-Jawahri Areej
Published: March 2020

11524

Background: Accurate prognostic understanding facilitates the receipt of goal-concordant medical care. Few studies have evaluated prognostic understanding in patients with hematologic malignancies. In this secondary analysis of a multicenter, longitudinal study of patients with hematologic malignancies referred for a second opinion hematology subspecialty consultation, we assessed changes in prognostic understanding after consultation, and predictors of post-consultation patient-oncologist prognostic discordance. Methods: Patients were recruited from 4 academic centers. Before and 1-7 days after consultation, patients were asked about their perceived chance of cure (options < 10%, 10-19%, and up to 90-100% in 10% increments, and “do not wish to answer”). Oncologists were asked the same question after consultation. Discordance was defined as a difference in response by 2 levels in the patient-oncologist dyads. We used multivariate analysis to assess the demographic and clinical predictors of patient-oncologist discordance. Results: We included 216 patients (median age 55 years, range 22-79) and 46 oncologists (47, 30-70). Overall, ≥On multivariate analysis, discordance before consultation [Odds Ratio (OR) 6.05, 95% Confidence Interval (CI) 2.96-12.36) and < college education (vs. post-graduate education; OR 2.34, 95% CI 1.09-5.14) were associated with discordance after consultation. Other patient demographics, comorbidity, cancer type, psychological distress, social support, decision-making preference, and coping strategies were not associated with discordance. Conclusions: Patient-oncologist concordance in prognostic understanding improved after subspecialty consultation, but over half of patients’ views of their prognosis remained discordant with those of their oncologists. Interventions to improve patient-oncologist communication about prognosis are needed, especially in patients with lower education level.
Comparing nonverbal synchrony in racially concordant and racially discordant oncology interactions.
Authors: Hamel Lauren M. , Moulder Robert , Eggly Susan , Albrecht Terrance Lynn , Boker Steven , Dougherty David W. , Penner Louis
Published: March 2020

11525

Background: Communication in racially discordant (Black patient, non-Black physician) oncology interactions, which constitute about 80% of Black patients’ interactions, is generally poorer than in racially concordant interactions, and likely contributes to treatment disparities. However, the nonverbal behaviors that contribute to this problem are largely unknown. We examined nonverbal synchrony, or the nonconscious coordination of movement, which can reflect relationship quality. We hypothesized that racially discordant interactions will have lower levels of nonverbal synchrony. Methods: Data include video recordings of 68 Black patients and 163 White patients discussing treatment with their non-Black oncologists. Recordings were submitted to motion detection software to measure nonverbal synchrony. This software measures global synchrony (all correlated motion), peak synchrony (all positively correlated motion), who is leading the interaction (similar to who is leading in ballroom dancing), and how much synchrony occurs based on who is leading the interaction. Using multi-level models, we investigated whether nonverbal synchrony differed in racially concordant and racially discordant dyads. Results: Findings showed greater levels of global synchrony (p < .05) and greater peak synchrony (p < .05) in racially discordant interactions compared to racially concordant interactions. Global synchrony was the same in racially concordant interactions regardless of who was leading, but greater global synchrony occurred in racially discordant interactions when the patient was leading (p < .05). Conclusions: This is the first study to use a dynamic jointly determined measure of behavior to assess oncology interactions. Contrary to our hypothesis, nonverbal synchrony was greater in racially discordant interactions than in racially concordant interactions. It appears patients are driving more of the synchrony in racially discordant interactions. This may suggest that patients in racially discordant interactions adapt to their physicians to bridge racial differences. Findings could contribute to physician training to enhance coordination and outcomes in oncology interactions.
ELAN-ONCOVAL (Elderly Head and Neck Cancer-Oncology Evaluation) study: Evaluation of the G8 screening tool and the ELAN geriatric evaluation (EGE) for elderly patients (pts) with head and neck squamous cell carcinomas (HNSCC).
Authors: Mertens Cécile , Le Caer Hervé , Ortholan Cécile , Blot Emmanuel , Even Caroline , Rousselot Hubert , Peyrade Frederic , Sire Christian , Cupissol Didier , Pointreau Yoann , Debourdeau Philippe , Rolland Frederic , Fayette Jerome , Capitain Olivier , Sun Xu Shan , Debbah Moufida , Boulahssass Rabia , Schwob Dominique , Auperin Anne , Guigay Joel
Published: March 2020

11541

Background: About 47% and 10% of HNSCC occur in pts aged ≥65 or ≥80 respectively. This population being heterogeneous, balancing efficacy with toxicity is challenging. As the G8 screening tool includes 3 nutritional items, we need to evaluate its usefulness in HNSCC pts and to establish an adapted tool for HNSCC pts. Methods: ONCOVAL is the first step of the ELAN program for pts ≥70 with HNSCC not amenable to surgery. Pts were assessed for geriatric frailties before inclusion in appropriate trials (ELAN-RT, FIT, UNFIT) depending on curative or palliative setting and fit or unfit status. The aim was to evaluate the G8 tool and EGE usable by oncologists to classify pts as fit or unfit. The EGE was elaborated by the French GERICO group for HNSCC pts, evaluating functional status, comorbidity, cognition/mood, social status. To estimate sensitivity and specificity of G8 and EGE, we used comprehensive geriatric assessment (CGA) performed by geriatricians as gold standard. Results: From 06/2013 to 08/2018, 633 pts were included in 44 centers. Data are available for 613 pts. Median age 79 years (70-97) with 45% ≥ 80. 75% males. G8 score was ≤14, i.e. at risk of geriatric frailty, in 82% pts. Assessment by EGE was done by physicians (64%), nurses (11%), ELAN staff (21%) in 20 minutes of median time. After EGE, oncologists classified 71% pts as unfit. 49% of pts were assessed by CGA. The G8 score with cut-off ≤ 14 has sensitivity 91% and specificity 30%. Lowering cut-off to 12 increased specificity to 56% but decreased sensitivity to 75%. Sensitivity of EGE was 95% and specificity 60%. Multidisciplinary interventions were more frequently implemented in pts assessed by geriatricians than in others (71% vs 47%), even after adjusting for frailty. 58% of pts included in ONCOVAL were further included in ELAN therapeutic trials. Assessment by geriatricians did not modify the rate of inclusion in trials. Conclusions: The G8 screening tool is not appropriate for HNSCC pts. The EGE was feasible and had better sensitivity and specificity. Oncologists and geriatricians must continue such collaboration to propose tailored treatments. Clinical trial information: NCT03614936.
Associations of uncertainty with psychological status and quality of life (QoL) among 527 older patients with advanced cancer.
Authors: Babu Dilip Sankar , Loh Kah Poh , Bautista Javier , Xu Huiwen , Culakova Eva , Canin Beverly E. , Conlin Alison Katherine , Bearden James , Berenberg Jeffrey L. , Zhang Yingzi , Wells Megan , Epstein Ronald M. , Dale William , Duberstein Paul , Mohile Supriya Gupta , Tejani Mohamedtaki Abdulaziz
Published: March 2020

11544

Background: Older patients with advanced cancer face considerable uncertainty related to their disease and treatment. The aim of our study was to evaluate the associations of uncertainty with psychological status and QoL. Methods: This is a secondary analysis of baseline data from a national geriatric assessment (GA) cluster randomized trial (URCC 13070; PI: Mohile). Patients aged ≥70 years with ≥1 GA domain impairment (e.g., function, cognition) and advanced cancer who were considering or receiving any line of cancer treatment were enrolled (n=541). Uncertainty was measured using the modified 9-item Mishel Uncertainty in Illness (MUIS), where respondents with higher scores perceive more uncertainty (range 9-45). QoL and psychological measures consisted of Functional Assessment of Cancer Therapy-General (FACT-G), emotional wellbeing (EWB; FACT-G subscale), distress (distress thermometer), anxiety (Generalized Anxiety Disorder-7), and depression (Geriatric Depression Scale-15). Multiple linear regressions were used to evaluate the associations of MUIS scores with each measure, adjusted for demographics, cancer type, and number of impaired GA domains. Results: Mean age was 77 years (SD 5, range 70-96); 26% had gastrointestinal cancer and 26% had lung cancer. Mean number of GA domain impairments was 4 (SD 1, range 1-7). Mean MUIS score was 20 (SD 5, range 9-37). On multivariate analyses, higher MUIS score was associated with lower QoL (β=-1.08, SE=0.11) and EWB (β=-0.29, SE=0.03), as well as higher distress (β=0.12, SE=0.02), anxiety (β=0.11, SE=0.04), and depression (β=0.09, SE=0.03; all P<0.01). Conclusions: Distress associated with uncertainty was common in a vulnerable population of frail older patients with advanced cancer and ≥1 GA domain impairment. A higher degree of uncertainty was associated with poorer psychological health and QoL. Our results underscore the important role that uncertainty plays in older patients' psychological status. Previous tested uncertainty management interventions (mainly including information and coping strategies) could be revised, tailored and tested to meet the unique needs of older patients with cancer. Clinical trial information: NCT02107443.
High temporal variability of clinical side effects with and without adjuvant chemotherapy in 4,684 early breast cancer patients in the CANTO trial.
Authors: Cottu Paul H. , Tanguy Marie-Laure , Laas Enora , Tredan Olivier , Giacchetti Sylvie , Guillermet Sophie , Ferrero Jean-Marc , Rigal Olivier , Tarpin Carole , Campone Mario , Levy Christelle , Soulie Patrick , Vanlemmens Laurence , Fournié Marion , Jouannaud Christelle , Everhard Sibille , Lemonnier Jerome , Arveux Patrick , Luis Ines Maria Vaz Duarte , Andre Fabrice
Published: March 2020

11566

Background: CANTO (CANcer TOxicities - NCT01993498) is a French multicenter prospective longitudinal study dedicated to the quantification and characterization of side effects after treatment for patients with stage I-III breast cancer, and to the development of predictors of toxicities. Methods: The CANTO study has included > 12,000 patients, assessed at diagnosis, and 3-6 months (T0), 15 months (T12), and year 3 and 5 after treatment completion. In the current report, we focus on key toxicities at T0 and T12 according to chemotherapy (CT) administration. For each side effect, 4 populations were defined according to its occurrence at T0 and/or T12 (no/no, no/yes, yes/no, yes/yes). Results: We analyzed 4684 patients with T0 and T12 consolidated data. Median age at diagnosis was 57y (22-89). Patients (pts) had HR+/HER2-, HER2+ or triple negative tumors in 78.9%, 12.4% and 8.7% of cases, respectively. Overall, 2516 pts (53.7%) received CT. Most CT pts (81%) received a sequential anthracyclines– taxanes schedule. As an example, a high proportion of patients presented neurological symptoms including cognitive symptoms, sensory or motor neuropathy, paresthesia, headache, etc (all grades) at either T0 or T12. Overall, CT was strongly associated with neurotoxicity at all times (OR = 2.27, p < 0.0001). However, proportions of patients with neurological side effects changed between T0 and T12. The table shows the proportions of the 4 categories of pts in the CT and no CT groups. Furthermore, at T12, neurological symptoms remained more frequent in the CT group, whether pts had symptoms at T0 (CT vs no CT, 81% vs 77%, p = 0.007) or not (CT vs no CT, 41% vs 36%, p = 0.03). Similar temporal trends were observed (with specific percentages for each considered side effect) for detailed neurological toxicities, pain and joint/bone toxicity (stratified on endocrine therapy), gastro-intestinal, pulmonary and cardiac toxicities. Conclusions: Overall, symptoms burden is extremely high at T0 and T12 after treatment, and much higher in pts receiving CT. A high temporal variability was observed in all subsets, including a clinically meaningful delayed onset of e.g. neurological side effects. Clinical trial information: NCT01993498. [Table: see text]
Single-fraction stereotactic versus standard conventional multifraction radiation for predominantly non-spine bone metastases: A randomized phase II trial.
Authors: Nguyen Quynh , Chow Edward , Chun Stephen G. , Liao Zhongxing X. , Fnu Rensi , Welsh James William , Hahn Stephen , Fuller Clifton David , Moon Bryan , Bird Justin E. , Satcher Robert L. , Lin Patrick P. , Jeter Melenda , O'Reilly Michael , Lewis Valerae O.
Published: March 2020

11578

Background: There lacks a consensus as to the optimal radiotherapy dose and fractionation schedule for treating bone metastases. We assessed the relative efficacy of single high-dose stereotactic radiation therapy (SBRT) versus standard multifraction radiation therapy (MFRT) for alleviation of pain in patients with mostly non-spine bone metastases. Methods: This prospective, randomized, single-institution phase II non-inferiority trial enrolled patients with radiologically confirmed painful bone metastases from September 2014 through June 2018. Patients were randomly assigned in a 1:1 ratio to receive either single-fraction SBRT (12 Gy for ≥4-cm lesions or 16 Gy for < 4-cm lesions) versus MFRT to 30 Gy in 10 fractions. Results: The primary endpoint was pain response, defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose [MED]). Failure of pain response was defined as worsening pain score (≥2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of ≥50%; re-irradiation; or pathologic fracture. Among evaluable patients who received treatment per protocol, the single-fraction SBRT group had more pain responders (CR+PR) at 2 weeks (62% vs. 36% MFRT, P= 0.01), at 1 month (62% vs 36%, P= 0.01), at 3 months (72% vs. 49% MFRT, P= 0.03), and at 9 months (77% vs. 12% MFRT, P= 0.03). No differences were found in treatment-related toxicity or quality of life scores after SBRT versus MFRT; local control rates at 1 year were higher in patients receiving single-fraction SBRT. Conclusions: Delivering high-dose single-fraction SBRT is an effective, convenient treatment option for patients with painful bone metastases. Among evaluable patients, SBRT led to higher rates of pain response (CR+PR) than did MFRT and thus should be considered for patients expected to have relatively long survival. Clinical trial information: ClinicalTrials.gov ID NCT02163226.
Correlates of distress for cancer patients: Results from multi-institution use of holistic patient-reported screening tool.
Authors: Weldon Christine B. , Gerhart James I. , Penedo Frank J. , Khosla Paramjeet , Roggenkamp Betty , Pasquinelli Mary , Martin Joanna , Lillis Teresa , Lo Shelly S. , Feldman Lawrence Eric , Deamant Catherine , Berardi Rosa , Miranda Harry , Newsom Carol , Bowman Anne , Trosman Julia Rachel
Published: March 2020

11587

Background: The Commission on Cancer (CoC) Standard 3.2 requires distress screening and indicated action for cancer patients. NCCN and ASCO supportive care and age-related guidelines include patient reported concerns beyond distress. This study compares PHQ4 scores to other patient reported concerns. Methods: The Coleman Supportive Oncology Collaborative aggregated “best of” screening tools to assess patient reported needs and concerns aligned with CoC, NCCN and ASCO guidance. This supportive care screening tool was implemented at 8 sites from July 2015 thru July 2018. Analysis used chi squared test. Results: Most patients, 86% (10,635/12,295), reported one plus concerns and/or above threshold scores on PHQ4, PROMIS Pain, Fatigue or Physical Function. A chi squared comparison of patients with at least mild distress on PHQ4 to patients with no distress resulted in p values < .0001 for every screening category. Conclusions: Patients with a PHQ4 distress score of mild, moderate or severe also reported statistically significant levels of practical, family, physical, nutrition and treatment concerns. These patients also scored threshold levels for PROMIS Pain, Fatigue, and Physical Function. Screening only for distress without screening for other patient concerns may direct patients to services that do not address or focus on the underlying cause of the distress. [Table: see text]
Survival and safety of monosialotetrahexosylganglioside in GI cancer patients with oxaliplatin-induced peripheral neurotoxicity-result from TJMUCH-GI-001 trial.
Authors: Likun Zhou , Huang Dingzhi , Liu Rui , Li Hongli , Ning Tao , Zhang Le , Ge Shaohua , Bai Ming , Wang Xia , Han Rubing , Yang Yuchong , Wang XinYi , Chen Xinyun , Gao Zhiying , Niu Kaijun , Luo Laizhi , Wu Xi , Deng Ting , Yang Yuanquan , Ba Yi
Published: March 2020

11596

Background: TJMUCH-GI-001 Trial was a randomized, double-blind, placebo-controlled phase III trial to study the efficacy of Monosialotetrahexosylganglioside (GM1) for oxaliplatin-induced peripheral neurotoxicity (OIPN) in GI cancer patients. Majority patients (> 80%) in both arms continued receiving oxaliplatin on the trial. The results showed GM1 effectively reduced OIPN in GI cancer patients. Here we report the survival and safety results of this trial. Methods: Patients were randomized in a 1:1 ratio to receive GM1 or placebo. Patients with OIPN > = G2 by CTCAE 4.03 persisting during or after oxaliplatin-based chemotherapy were eligible. The patients who remained on oxaliplatin after enrollment, received concurrent placebo or GM1 x 7 days with each chemotherapy cycle. The patients who stopped taking oxaliplatin, were treated with placebo or GM1 x 14 days every 3 weeks. GM1 was dosed at 60mg daily for every 3-week or 40mg daily for every 2-week schedule. Trial was continued until modified EORTC QLQ-CIPN20 ( MCIPN) increased by 30% or stayed unchanged after two more treatments beyond completion of oxaliplatin. Survival data for the treatment arms were compared using a log-rank test and Chi-square tests were used for safety analysis. Results: From May 2015 to Dec 2017, 73 patients were enrolled in GM1 and 72 in placebo arm. The median follow-up was 16.6 months (0.8-43.1 months) as of Dec.2018. Four patients lost to follow up. There was no deleterious impact of GM1 on survival. As a matter of fact, receiving GM1 was associated with a trend toward improved PFS and OS (HR=0.74,95%CI, 0.469 - 1.156 for PFS and HR=0.76, 95%CI0.469 - 1.156 for OS). The most frequent Grade 3 or 4 adverse events included neutropenia (8 patients in GM1 group VS. 4 in placebo group) and hypoleukemia (4 patients in GM1 group VS. 1 in placebo group). Other 3 or 4 adverse events (all less than 3 patients) included anorexia, hypercalcemia, nausea, vomiting, proteinuria, hyperbilirubinemia, hypokalemia, hypertension and appendicitis. All the 3 or 4 adverse events were related to chemotherapy, not to GM1. Conclusion: In this placebo-controlled phase III trial, GM1 showed acceptable toxicity with trends favorable PFS and OS in GI cancer patients. Clinical trial information: NCT02486198.
Phase 2 trial of Symptom screening with Targeted Early Palliative care (STEP) for patients with advanced cancer.
Authors: Zimmermann Camilla , Hannon Breffni , Krzyzanowska Monika K. , Li Madeline , Rodin Gary , Pope Ashley , Swami Nadia , Giruparajah Mohana , Howell Doris , Oza Amit M. , Warr David , Knox Jennifer J. , Leighl Natasha B. , Sridhar Srikala S. , Prince Rebecca M. , Lheureux Stephanie , Hansen Aaron Richard , Booth Christopher M. , Dudgeon Deborah Jane , Le Lisa W ,   STEP Trial Group
Published: March 2020

11604

Background: Routine early palliative care (EPC) by specialized teams improves quality of life for patients with advanced cancer, but may not be scalable. To plan for a larger randomized controlled trial, we conducted a phase 2 trial of STEP, a novel intervention of targeted EPC based on symptom screening. Methods: Participants with advanced cancer, ECOG 0-2, and clinical prognosis ≥6 months were recruited from lung, gastrointestinal, genitourinary, breast and gynecology outpatient clinics. Symptoms were screened at every outpatient visit using the Edmonton Symptom Assessment System-revised (ESAS-r). Moderate to severe symptom scores (≥4/10 for pain, nausea, dyspnea, depression, anxiety; ≥7/10 for fatigue, appetite, drowsiness, well-being) triggered an e-mail to a nurse, who called the patient, offering an EPC visit. Participants completed outcome measures at baseline, 2, 4 and 6 months (primary endpoint). Trial feasibility criteria were: i) ≥100 patients accrued in 12 months; ii) ≥70% complete screening for ≥70% of visits; iii) ≥60% of those for whom a call is triggered meet at least once with the EPC team; iv) ≥60% complete measures at each endpoint. Results: From 11/2016-1/2018, 116 patients were enrolled; 89/116 (77%) completed screening for ≥70% of visits and 59% (69/116) received a call triggered by symptoms. Of those receiving a call, 62% (43/69) received EPC; 3 further patients were referred by their oncologist. Measure completion was 79% (81/116) at 2, 61% (71/116) at 4, and 57% (66/116) at 6 months. By trial end (6 months), patients who received a call and accepted EPC involvement had better symptom control (ESAS-r-CS mean change in those receiving vs. deferring EPC: -0.07±16.9 vs 11.8±13.7, p = 0.02) and less deterioration in mood (PHQ-9: -0.4±3.4 vs 2.6±2.3, p = 0.003). There was no difference between those receiving versus deferring EPC in quality of life (FACIT-Sp: -4.7±13.6 vs -3.2±15.4, p = 0.75; QUAL-E: -2.6±8.4 vs -1.5±11.0, p = 0.62), or satisfaction with care (FAMCARE-P-16: -3.2±7.9 vs -3.5±6.1, p = 0.79). Conclusions: STEP is feasible in patients with advanced cancer. More than half of patients have moderate to severe symptoms, and acceptance of the triggered EPC visit should be encouraged.
Lower costs of care, improved discharge disposition, and improved survival of advanced cancer patients (ACP) receiving early inpatient palliative care (PC) compared to standard oncologic care (SOC).
Authors: Daugherty Christopher , Johnson Julie , Levine Stacie K. , Wroblewski Kristen , Lane Bradford , Dale William , Malec Monica , Hlubocky Fay J.
Published: March 2020

11609

Background: Outpatient PC improves ACP symptom burdens, end-of-life care transitions, and mortality thereby enhancing quality of life. Yet, the financial implications, discharge disposition, and survival benefits of early, inpatient PC compared to SOC remains less understood. Methods: Retrospective cohort analysis of ACP receiving either PC or SOC between Jan 2015-Dec 2015 (N = 810). ACP cohorts were compared for demographics, costs, disposition, and survival. Financial costs collected included: fixed (overhead expenditures, facility maintenance, hospital property); variable (patient care supplies, diagnostic/therapeutic supplies, medications); operating (fixed, variable, breaking-even costs); direct (labor, materials, commissions, piece-rate wages, manufacturing supplies); indirect (production-supervision salaries, quality control, insurance, depreciation). Univariate and multivariate analyses were completed. Results: 468 were admitted to PC and 342 to SOC. Compared with SOC, PC were more likely to be: younger (61.1±13.2 v. 62.5±13.0, p = 0.02); African American (48% v. 36%, p = 0.0045); female (50% v. 40%, p = 0.005); and have shorter length of stay (5.7±4.9 v. 6.2±6.5, p = 0.01). PC had significantly less 30-day readmissions (16% v 23%, p = 0.03) and lower costs: direct ($9,478 v. $10,416, p = 0.01); indirect ($9,538 v. $10,999, p = 0.002); fixed ($10,308 v. $12,076, p = 0.001); variable ($8,709 v. $ 9,339, p = 0.02); operating ($19,017 v. $21,416, p = 0.003).Compared with SOC, ACP receiving PC were more likely to be discharged to: home (55% v.45%, p = 0.01); healthcare facilities (e.g. skilled nursing, inpatient rehabilitation) (36.1% v. 20%, p = 0.04); and hospice (home and inpatient) (7.7% v 5.8%, p = 0.02). PC had overall greater median survival from the time of discharge (106.8±99.95 v. 73.8±61.93, p = 0.03) compared to SOC. Conclusions: Early PC results in less financial strain, greater cost savings, and improved outcomes for younger and underserved inpatient ACP. Our results provide additional evidence for policies supporting that ACP access to routine PC must become a healthcare priority.
Communicating Oncologic Prognosis with Empathy (COPE) Pilot Study.
Authors: Goodgame Boone W. , Phillips Farya , Zhang Wenhui Vivian , Jones Barbara L.
Published: March 2020

11613

Background: Multiple studies show that patients with advanced cancer often believe the goal of treatment is cure. Our interprofessional team designed the Communicating Oncologic Prognosis with Empathy (COPE) guide to enhance communication for patients, families, and the healthcare team. This unique, single-page tool allows treating physicians to estimate prognosis for patients, including likelihood of living 6 mo, 1y, 2y, and 5y, with or without treatment. Methods: Patients with incurable cancer were enrolled at one oncology clinic. Using a pre/post-test design, participants completed the validated prognosis and treatment perception survey (PTPQ) then met with their oncologist. The COPE guide was used for the discussion and the patient received a copy of the completed COPE. The COPE guide was placed in the patient chart and the healthcare team (social work, spiritual care etc.) used it to provide patient support and explore the patient’s response to the information. Post-test was completed 4-8 weeks later. Qualitative exit interviews were used to assess patient reported impact on communication with medical team, caregivers and family, and quality of life. Results: 43 patients were enrolled and 25 completed all study measures. All patients had advanced cancer with 96% of patients (24) extremely unlikely to be cured ( < 1% chance). Oncologist’s treatment goals were better quality of life and longer life. All participants completing the study found the communication guide helpful, scoring 9-10 out of 10. 95% of patients enrolled wanted to hear details about their prognosis. Pre-intervention, 28% (7) of patients reported their primary goal of treatment as cure (n = 7; 28%) or to extend life as long as possible (n = 7; 28%). Pre-intervention, patient’s perceptions of their oncologist’s goals of treatment were cure (n = 11; 44%) or extend life (n = 8; 32%). At post-test, 8% of participants (2) inaccurately reported goal of treatment as cure (p < 0.05). Conclusions: These findings highlight major gaps in patients’ understanding of their prognosis. COPE is a promising mechanism to enhance patient-centered communication about prognosis and treatment for patients with incurable cancer.