bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical behavior and treatment outcomes in angiosarcoma: A 10-year retrospective review.
Authors: Espejo Freire Andrea P. , Costa Philippos , Alasfour Maryam , Akgun Yamac , Rosenberg Andrew , Diaz-Perez Julio , Kwon Deukwoo , Subhawong Ty , Arshad Junaid , Trent Jonathan C.
Published: May 2020

e23555

Background: Angiosarcoma (AS) is a highly aggressive sarcoma. Five-year overall survival (OS) with local disease is only about 60% despite multimodality treatment. In advanced disease, responses to cytotoxic chemotherapy are common; however, median OS is only 3-12 mos. Targeted therapies (TT) have not been consistently effective. Early results for immune checkpoint inhibitors (ICI) are promising but their efficacy has not been compared to chemotherapy. Here we present the outcome of AS patients by systemic regimen and multimodality approach. Methods: We identified 39 patients with pathologically confirmed AS treated at Sylvester Comprehensive Cancer Center and Jackson Memorial Hospital from 2009 to 2019. Clinical characteristics, treatment, responses and survival were analized. We calculated OS using Kaplan-Meier method and statistical significance with Log-Rank Test and Cox regression to estimate hazard ratio (HR) and 95% confidence interval. Progression-free survival (PFS) was analyzed for different regimens in the palliative setting using same approach as for OS. Results: In our cohort, median follow-up is 2.3 years (95% CI = 2 to 3.3), 48% were women and median age at diagnosis was 63 (range 13-89). At presentation, 16 pts (41%) had local disease and 23 advanced or metastatic (59%). By location, 13 pts (33%) had primary cutaneous AS, 12 pts (31%) visceral AS, 5 pts (13%) primary breast AS, 2 (5%) extremity AS and 7 (18%) radiation associated AS. Multimodality treatment was used in 29 pts (74%). OS in the entire cohort at 3 years was 49% (95% CI = 28 to 67%). OS between local disease was (N = 16) and in advanced disease (N = 23) was not statistically significant (p = 0.485; HR = 1.1 [95% CI = 0.4 to 3.3]). In the neoadjuvant setting, objective response rates trended to favor doxorubicin-based regimen (DBR) over taxane-based regimens (TBR) (80% vs. 40%) but were not statistically different (p = 0.519). In the advanced setting, PFS for DBR was 3.9 mo (95% CI 1.1 to 4.9 mo), 5.9 mo for TBR (95% CI 2.3 to 10.9 mo), 6.1 mo for ICI (95% CI not estimable), and 2.4 mo for targeted therapy (TT) (95% CI 0.8 to 8.8 mo), most common TT agent was pazopanib (71% of TT agents). Conclusions: AS is highly aggressive and most patients with local presentation will relapse translating in similar OS to the advanced cohort. No significant activity was seen for TT. In the advanced setting, chemotherapy with TBR appears slightly superior to DBR. ICIs resulted in similar if not superior PFS despite its use in a later line setting. Studies incorporating ICIs into earlier lines of therapy are warranted.
The prognostic impact of unplanned excision in primary STS of the extremities and trunk wall: Is re-excision always mandatory?
Authors: Danieli Maria , Barretta Francesco , Fiore Marco , Radaelli Stefano , Callegaro Dario , Barisella Marta , Sangalli Claudia , Stacchiotti Silvia , Palassini Elena , Miceli Rosalba , Casali Paolo Giovanni , Gronchi Alessandro
Published: May 2020

e23557

Background: To investigate the outcome of patients affected by soft tissue sarcomas (STS) of the extremities and trunk wall who underwent unplanned excision (UE) and the prognostic impact of microscopic residual tumor at re-excision. Methods: All consecutive patients affected by primary STS of the extremity and trunk wall operated at Fondazione IRCCS Istituto Nazionale dei Tumori from Jan 1997 to Dec 2017 were included and divided in 3 groups: patients primarily resected at our institution (group A), patients undergoing re-excision after macroscopically complete UE (group B) and patients undergoing completion resection after macroscopically incomplete UE (group C). Inverse probability treatment weighted overall survival (OS), crude cumulative incidence of local relapse (CCI-LR) and of distant metastasis (CCI-DM) were calculated and compared. Histological subgroup curves were drawn and multivariable models were performed in group B. Results: 1965 patients were identified; 1079, 679 and 189 in group A, B and C respectively. Median follow-up was 84.41 months. 7-yrs OS was 0.74, 0.84 and 0.81 (p < .001) for group A, B and C respectively; 7-yrs CCI-LR and DM were 0.05 and 0.25, 0.12 and 0.16, 0.14 and 0.29 (p < .001 for both) for group A, B and C respectively. In group B, microscopic residual tumor was present in 26.9% of the surgical specimens, but this figure varied broadly among the histologic subtypes (being the lowest in Solitary Fibrous Tumor, 7.7%, and the highest in Myxofibrosarcoma [MFS], 46.5%). At multivariable analysis, age (for OS only), grade, size and histology were associated to OS and CCI-DM; while age, presence of residual tumor (p < .001) and grade to CCI-LR. Of note, Myxoid liposarcoma (MLPS) and MFS showed the highest CCI-LR in presence of residual disease (18.6% vs 1.3% and 24.7% vs 7.2% respectively). Conclusions: Patients who underwent UE had a risk of LR twice as high as those primarily resected at a referral institution. However, this higher risk was not associated to a higher risk of DM or worse OS. In patients undergoing re-excision after macroscopic complete UE the presence of residual tumor was associated to a higher LR risk, again with no association with DM or OS. Despite the probable presence of a residual selection bias, it is possible that postponing re-excision after macroscopic complete UE doesn’t impact on the outcome. However, higher caution should be exerted for MLPS and MFS, given the higher probability of local relapse when microscopic residual tumor is found in the surgical specimen.
Analysis of signaling pathway activity in desmoid-type fibromatosis (DF) to identify druggable pathways.
Authors: Van De Stolpe Anja , Akse Martijn , den Biezen-Timmermans Eveline , Blay Jean-Yves , Penel Nicolas
Published: May 2020

e23558

Background: DF are locally invasive soft tissue tumors of fibroblast origin, with unpredictable course. CTTNB1 mutations are a hallmark of DF. Molecular-targeted therapies are lacking. Recently developed OncoSignal (www.philips.com/oncosignal) pathway activity tests enable quantitative measurement of activity of clinically relevant oncogenic signal transduction pathways (estrogen, progesterone & androgen receptors; PI3K, MAPK-AP1, TGFβ, Notch, Hedgehog, Wnt pathways), based on computational interpretation of expression levels of direct target genes of the pathway-associated transcription factor. Methods: OncoSignal was used to measure activity of signaling pathways on Affymetrix transcriptome data from sporadic DF (n = 128), generated before in our center (GEO database: GSE58697), and from presumably healthy fibroblasts (n = 63) derived from a number of different tissue types (public dataset GSE63626). Pathway activity was expressed on a normalized scale 0-100 (min and max pathway activity score depend on the cell/tissue type analyzed). Comparisons used Mann Whitney test. Results: Mean Notch (43.2+/-7.2 vs 11.2 +/- 5.2; p < .0001), PI3K (54.6 +/- 10.0 vs 48.1 +/- 6.6, p < .0001) and androgen receptor (AR) pathway activities (32.8 +/- 3.7 vs 21.7 +/- 2.4, p < .0001) were increased in DF compared to fibroblasts. MAPK-AP1 pathway activity was lower in DF (40.8+/-6.0 vs 70.2 +/- 9.5; p < .0001). Mean Wnt (p = 0.7), HH (p = 0.8) pathway activities were not different between DF and fibroblasts, however the range in Wnt pathway activity scores was larger in DF (median score 24.1, range 5.3-41.7) than in normal fibroblasts (median 26.0, range 14.6-33.0). Conclusions: The increased activity of Notch, PI3K pathways in DF is consistent with the mesenchymal nature. We confirm here the key role of AR pathway. The wide range of Wnt pathway expression was larger, suggesting the heterogeneity in TD biology, possibly related to the type of CTTNB1 mutations. Overall, the large inter-patient variation in pathway activities is in line with variety of TD course. We identified signaling pathways which may provide novel options for targeted drug treatment.
Radiochemotherapy with gemcitabine as radiosensitizer in patients with soft tissue sarcoma.
Authors: Augustin Marinela , Wilhelm Martin , Reichert Bert , Siegler Gabriele Margareta , Dreier Juergen , Rottmann Michael , Blos Martin , Kalisch Alexander , Dressler Sabine , Stein Hubert , Koehler Jens , Papadopoulos Thomas , Meyer Christian , Hohenberger Peter , Jakob Jens , Vassos Nikolaos , Grehn Christian , Albrecht Clemens
Published: May 2020

e23559

Background: Radiation therapy is an essential backbone of the management of patients (pts.) with soft tissue sarcoma (STS) as part of a multimodal curative or palliative treatment. Concurrent external-beam radiation therapy (EBRT) and chemotherapy with doxorubicin (doxo) and ifosfamide (ifo) may be indicated as well, but is associated with relevant toxicity. Gemcitabine (gem) is a known radiosensitizer and has shown activity in STS. The purpose of this study was to evaluate the efficacy and toxicity of concurrent EBRT and gemcitabine. Methods: A single center, retrospective analysis of 12 patients (pts) with STS treated with concurrent EBRT and gemcitabine from Nov 2017 to Dez 2019 in a neoadjuvant (6 pts) or palliative setting (6 pts). Gemcitabine (gem) was administered with 150-300mg/m2 once weekly for the duration of the EBRT (50 Gy in 25 fractions over 5 weeks). In the neoadjuvant treated group, 4 pts had undifferentiated pleomorphic sarcoma (UPS) G3, 1 leiomyosarcoma (LMS) G2 and 1 retroperitoneal G1 liposarcoma (LPS). The pts. were either not eligible for a neoadjuvant systemic treatment with doxo/ifo or received the EBRT/gem treatment in addition to it. Results: 5/6 pts. with neoadjuvant EBRT/gem had R0 resection and 1/6pt. R1. The IUCC stage was IIIB in 5/6 pts and IB in 1/6 pt. The tumor regression grade (TRG) was > 99% in 3/4 pts. with UPS G3 (75%) and 80% in 1/4 pt. with UPS G3. The TRG for the G2 LMS and for the G1 LPS was 20%. All pts treated in palliative setting had high grade sarcoma and responded to the treatment with partial remission, the 6 months’ local control rate was 83% (5/6 pts) for symptomatic fast growing lesions, 1/6 pt. being in PR at 4 months follow up. The combination treatment was well tolerated with reversible skin toxicity CTCAE grade I. As expected transient thrombocytopenia was observed without limiting effect on the planned EBRT. Conclusions: The combination therapy of EBRT and gemcitabine as sensitizer in pts. with STS is feasible und well tolerated. The treatment is an option for patients not eligible for neoadjuvant systemic treatment with doxo/ifo and in the palliative setting as well. It might be more potent than radiation only in achieving tumor regression and local control for high grade STS.
HLA genotyping in synovial sarcoma: Identifying HLA-A*02 and its association with clinical outcome.
Authors: Rosenbaum Evan , Seier Kenneth , Bandlamudi Chaitanya , Chi Ping , Dickson Mark Andrew , Gounder Mrinal M. , Kelly Ciara Marie , Keohan Mary Louise , Movva Sujana , Nacev Benjamin , Slotkin Emily Kanaya , Simeone Noemi , Donoghue Mark , Qin Li-Xuan , Antonescu Cristina R. , Tap William D. , D'Angelo Sandra P.
Published: May 2020

e23560

Background: Patients (pts) with synovial sarcoma (SS) and an HLA-A*02 genotype whose tumors express NY-ESO-1 may be eligible for clinical trials of adoptive T cell therapy. We reasoned that a next generation tumor sequencing platform utilizing matched normal DNA (MSK-IMPACT) could accurately identify HLA genotype. Although HLA-A*02 is necessary for some adoptive T cell therapies, the prognosis of this genotype on clinical outcome has not been described in SS. Methods: Pts with metastatic SS who consented to screen for a clinical trial of engineered T cells had high-resolution HLA genotyping performed with a Clinical Laboratory Improvement Amendments (CLIA)-certified test. Where feasible, HLA genotype and loss-of-heterozygosity (LOH) of HLA alleles were determined from IMPACT samples. Overall survival (OS) was estimated in three overlapping cohorts and stratified by HLA-A*02 status: pts treated with anthracyclines or alkylators in the first line, pazopanib in the second line or beyond, and all pts from time of metastasis. Results: 66 pts with SS were screened, but not treated with T cells; 30% (n = 20) were HLA-A*02-positive on a CLIA-certified outside test. 23 pts had HLA genotyping both by IMPACT and an outside laboratory, 22 (96%) of whom had concordant results. 3 pts had LOH of at least 1 HLA allele, including one with LOH of HLA*02:01 in the primary tumor. Among pts treated chemotherapy (n = 36) or pazopanib (n = 37), OS did not significantly differ between HLA-A*02-positive or negative pts. Univariable analyses of OS from the time of metastasis in the whole cohort identified primary tumor size and time to metastasis as variables significantly associated with outcome (hazard ratio (HR) 1.2, 95% confidence interval (CI) 1.123 – 1.345 [P < 0.001] and HR 0.99, 95% CI 0.976 – 0.999 [P = 0.032], respectively). HLA-A*02-positive status and age did not reach the significance threshold (HR 1.95, 95% CI 0.995 – 3.813 [P = 0.052] and HR 1.021, 95% CI 0.999 – 1.044 [P = 0.061], respectively). Multivariable analysis found older age and larger tumor size were independently associated with significantly shorter OS (HR 1.03, 95% CI 1.002 – 1.049 [P = 0.037] and HR 1.2, 95% CI 1.127 – 1.37 [P < 0.001], respectively). Conclusions: Targeted exome panels like IMPACT that utilize matched tumor-normal DNA may accurately identify HLA genotype. Detection of LOH at HLA loci may identify a subgroup of pts who would be refractory to treatment with HLA-A*02-restricted engineered T cells. HLA-A*02 status was not associated with a statistically significant survival difference in pts with metastatic SS.
Irinotecan and temozolomide upfront and in relapsed Ewing sarcoma: A translational study on MGMT (O6-methylguanine–DNA methyltransferase) and ABCG2 (MGMTLiberati).
Authors: Palmerini Emanuela , Pasello Michela , Jones Robin Lewis , Manara Maria Cristina , Fagioli Franca , Grignani Giovanni , Longhi Alessandra , Cesari Marilena , Abate Massimo Eraldo , Paioli Anna , Setola Elisabetta , Hakim Rossella , D'Ambrosio Lorenzo , Parra Alessandro , Sebastian Asaftei Dorin , Righi Alberto , Morandi Luca , Donati Davide Maria , Ferrari Stefano , Scotlandi Katia
Published: May 2020

e23564

Background: Activity of temozolomide (TEM) and irinotecan (IRI) in recurrent Ewing sarcoma (EWS) was demonstrated. Few data are available on TEMIRI use upfront. Biological predictive factors are lacking. Methods: This multi-institutional retrospective study (NCT03542097) included 59 patients with EWS. 8 patients with very high risk (HR) EWS (multivisceral ± bone marrow) received TEMIRI (TEM 100 mg/m2/day oral, and IRI 40 mg/m2/day intravenous, days 1-5, every 21 days) upfront, 51 patients after relapse (28% in 1st line, 72% ≥ 2nd line). Overall response rate (ORR: CR+PR), SD, and PD, progression-free (PFS) and overall survival (OS) were assessed. The relationship between pre-treatment expression of MGMT and ABCG2 (when FFPE tissue available) with ORR, PFS and OS was evaluated. Results: Median age was 27 years (range 4-62 years): 47 patients (80%) were adults (≥18 years), 35 (61%) had ECOG 0 and 42 (71%) presented with multivisceral disease (+ bone marrow in 5). MGMT was positive in 16/30 (53%), ABCG2 in 4/33 (12%). ORR for upfront TEMIRI (n = 8) was 50% (CR + PR = 1 + 3), with SD 50%, while in recurrent EWS (n = 49, 2 patients no measurable by RECIST) ORR was 31% (CR + PR = 4 + 11), SD 38%, and PD 31%. A better ORR was observed in adult (p = 0.008) & ECOG 0 (p = 0.001) patients; MGMT & ABCG2 expression did not influence ORR. 6-mos PFS was 87% after TEMIRI upfront, 43% at recurrence (p = 0.06), and 65% vs 28% (p = 0.02) for ECOG 0 vs ECOG 1-2, respectively. 6-mos PFS was 62% in MGMT+ vs 33% in MGMT- (p = 0.4) and 75% in ABCG2+ vs 50% in ABCG2- (p = 0.7). Median time to progression (TTP) with upfront TEMIRI was 9 months (range 5-28 months), with 1 patient with ongoing CR at 56 months; median TTP at relapse was 3 months (1-29 months). MGMT and ABCG2 expression did not influence 1-yr OS, whereas ECOG (0 vs 1-2) did (88% vs 31% p < 0.001). Grade 3-4 diarrhea, neutropenia, and thrombocytopenia incidence was < 5%, 1 patient with recurrent kidney EWS died of acute liver failure. Conclusions: TEMIRI showed promising activity in a very unfavorable cohort of EWS patients, with manageable toxicity. Performance status correlated with 6-month PFS & OS whereas MGMT & ABCG2 did not. Clinical trial information: NCT03542097 .
Role of glyoxalase-1 in trabectedin-resistant myxoid liposarcoma.
Authors: Simonetti Sonia , Iuliani Michele , Pantano Francesco , Ribelli Giulia , Napolitano Andrea , Santini Daniele , Tonini Giuseppe , Vincenzi Bruno
Published: May 2020

e23566

Background: Glyoxalase-1 (Glo1) is involved in the detoxification of the endogenous reactive metabolite, methylglyoxal (MG), whose abnormal accumulation increases adduct levels and induce cell apoptosis. Previous studies demonstrated that increased Glo-1 expression was associated with cancer chemotherapy resistance. We performed bioinformatics analyses finding that Glo-1 mRNA over-expression was correlated with worse prognosis in patients affected by Soft Tissue Sarcoma (STS). On the bases of these evidences, we investigated the potential role of Glo1 expression as biomarker of tumor growth and drug resistance in STS. Methods: Trabectedin and MG cytoxicity was evaluated by MTT viability assay measured at spectrofluorometer. Apoptosis was analyzed by flow cytometry using Annexin V antibody and propidium iodide. Glo-1 expression analysis was performed by Western Blot using a mouse monoclonal anti-human Glo-1 antibody (NBP1-19015). Synergy analysis was calculated using Combenefit software and statistical analysis was performed by Student-t test using the program GraphPad-Prism. Results: As STS trabectedin resistant model, we used a myxoid-liposarcoma cell line (402-91 ET cells) that are not responsive to clinical doses of trabectedin contrary to the parental sensitive cell line (402-91 WT cells). Intriguingly, we found higher Glo-1 protein levels in 402-91 ET cells compared to 402-91 WT cells. The treatment of 402-91 ET cells with the specific Glo1 inhibitor S-p-bromobenzylglutathione cyclopentyl diester (BBGC), in combination with trabectedin (PharmaMar), significantly inhibited cell viability and increased apoptosis than trabectedin alone. In particular, the addition of BBGC reduced trabectedin EC50 (half-maximal effective concentration) from 20.4nM to 5.92nM in 402-91 ET cells, similar to that observed in 402-91 WT cells (4.92nM). To investigate if cell death was induced by MG accumulation following Glo1 inhibition, we evaluated 402-91 ET cell viability after treatment with different doses of MG in combination with trabectedin. The addition of MG restored sensitivity to trabectedin in 402-91 ET cells as well as BBGC. Conclusions: Our results highlight a new potential mechanism of trabectedin resistance mediated by Glo-1 over-expression. The use of the specific Glo-1 inhibitor, BBGC, restores trabectedin sensitivity in resistant cells leading to MG accumulation that, in turn, promotes cell death and apoptosis. These data provide a strong rationale to investigate Glo-1 inhibition strategy, in combination with trabectedin, in STS in vivo models.
Effect of beta blocker use in soft tissue sarcomas.
Authors: De Leo Edward , Hanayneh Wissam , Shah Chintan , Wang Yu , Lee Ji-Hyun , Close Julia Lee , Dang Nam H.
Published: May 2020

e23571

Background: Soft tissue sarcomas (STS) are a rare, heterogenous group of cancers that tend to have a poor prognosis and few effective treatment strategies. Beta blockers (BB), in particular non-selective BB such as propranolol, have been shown to have an antitumor effect in different malignancies, including breast, colon, and angiosarcomas. The underlying mechanism is unclear but it is thought to be related to the inhibition of beta receptors on malignant cells, which leads to decrease in tumor vascularity and hematogenous spread. In this retrospective analysis, we examined the effect of BB on the outcomes of STS at a tertiary referral center. Methods: Adult patients from 2000 through 2019 with a diagnosis of STS with adequate follow up were included, and were divided into 2 groups: patients on BB at any point during treatment and/or up to 6 months prior to diagnosis, and patients without BB. The patient and tumor data were extracted and analyzed. The primary outcome was overall survival (OS). Statistical methods included descriptive analysis, univariable and multivariable Cox proportional hazard regression analyses and Kaplan-Meier survival plots. Results: 448 patient charts were analyzed. Median age at diagnosis was 55 (range 18-89). 54% were male. 4.9% of patients were diagnosed with stage 4 disease. Histologies included: undifferentiated pleomorphic sarcoma 26.1%, leiomyosarcoma 10%, synovial sarcoma 9.2%, liposarcoma 7.8%, osteosarcoma 2.7%, Ewing sarcoma 2% and others 42.2%. 18.1% of patients were on BB during treatment, with metoprolol the most commonly used (59%). 96% of patients on BB had HTN and 44% had coronary artery disease. Patients on BB were less likely to receive adjuvant therapy (18% vs 26%). Patients on BB were more likely to have stage 4 disease at presentation (9.9% vs 3.8%). Multivariate analysis showed there was no significant difference in overall survival between patients on BB and those not on BB, HR 1.3 (CI 0.8-2.1, p = 0.24). Conclusions: There is no difference in overall survival in patients on beta blockers during treatment for STS after controlling for stage, comorbidities, smoking, and age. Further studies are needed to evaluate the effect of specific beta blocker drugs on soft tissue sarcoma outcomes.
Qualitative patient interviews on symptoms and impacts in metastatic synovial sarcoma (mSS).
Authors: Becker Brandon , Eliason Laurie , Culver Kenneth W. , Arbuckle Rob , Francis Anya , Pokras Shibani
Published: May 2020

e23576

Background: Synovial sarcoma (SS), a soft tissue sarcoma, is a rare and aggressive malignancy, with significant morbidity and mortality associated with mSS. There are currently no patient-reported outcome (PRO) instruments specific to mSS patients and little qualitative research to understand impacts on mSS patients’ health-related quality of life (QoL). The objective of this study was to characterize the symptoms and impacts experienced by mSS patients to inform the selection of content-valid PRO instruments for use in investigational trials in mSS patients. Methods: This was a non-interventional, qualitative interview study of adult participants in the United States (US) with physician-confirmed mSS. Participants were consented from a large private practice in the US. Six semistructured concept elicitation interviews (60–90m by telephone) were conducted by trained interviewers. Participants were asked to describe their mSS symptoms and their impact on functioning in an open-ended fashion with follow-up probes. Verbatim transcripts were analyzed using thematic analysis methods and Atlas.Ti software. Socio-demographics and clinical characteristics were collected by the site. The study received Institutional Review Board (IRB) approval from Western IRB. Results: Among the 6 participants, average age was 45y (range 21–61y) and 2 were female. All 6 participants had pulmonary metastasis, 1 participant had a liver metastasis, and 1 participant had a mediastinal mass. The most common symptoms participants spontaneously identified were pain (n = 6), fatigue (n = 6), coughing (n = 5, with 2 upon probing), shortness of breath (n = 4), phlegm/mucus in the lungs (n = 3), coughing up blood (n = 2), and gastrointestinal complications (n = 2). Nerve/shooting/burning pain (n = 5) was mentioned upon probing. Participants also reported impacts of their disease on sleep (quantity and quality) (n = 6), physical activity (n = 6), social life (n = 6), daily activities (n = 5), emotions (n = 5), loss of appetite (n = 3), and finances (n = 1). Although not spontaneously reported, global ratings of overall health and QoL were considered relevant by all participants. Conclusions: This is the first study to identify patient-relevant symptoms and impacts associated with mSS. Further interviews with additional participants are ongoing, and we will analyze these data to identify appropriate PRO instruments for use in investigational trials in mSS patients. Funding: GlaxoSmithKline (209386).
End-of-life care in the immune checkpoint inhibitor era.
Authors: Buckenheimer Alyssa , Dothard Andy Shipe , Russell Gregory , Grey Carl , Petty William J. , Lycan Thomas
Published: May 2020

e24003

Background: Immune checkpoint inhibitors (ICI) can lead to durable responses in some patients with advanced non-small cell lung cancer (NSCLC) with less toxicity than chemotherapy. However, ICI can cause idiosyncratic adverse effects and radiographic responses can be difficult to interpret, making prognostication difficult and potentially impeding a timely transition to hospice. Our purpose was to explore end of life (EOL) outcomes in NSCLC patients treated with ICI. Methods: Retrospective data were collected on all patients with NSCLC started on ICI at single center (2014-2018) and who died before last known follow-up. EOL outcomes included hospitalizations, ICU admissions, timing/location of hospice referral and death. Charts were reviewed to identify barriers to hospice referrals or enrollment. Outcomes were compared to published data of similar cohort (2008-2010) from same institution treated with chemotherapy. Results: Out of 143 patients who died, 83 (58%) had internal hospice referral by cancer center; 15 (11%) were referred by external provider. Hospitalization frequency was associated with higher likelihood of internal hospice referral (p 0.04). Internal hospice referral was not associated with differences in age, sex, race, ethnicity, smoking history, cancer subtype, treatment response/toxicity, or overall survival. Internal hospice referral was associated with decreased rates of death on the hospital floor (p < 0.001) and the intensive care unit (ICU, p < 0.001). When compared to chemotherapy cohort, there was similar rate of hospice referral (68% vs. 74%, p 0.33) but higher rates of starting new systemic therapy within 30 days of death (17% vs. 6%, p 0.001) and last dose within 14 days of death (13% vs. 5%, p 0.005). Other EOL outcomes (hospitalization frequency, death in ICU) were similar, although ICI cohort trended towards a lower rate of death on the floor than chemotherapy cohort (16% vs. 25%, p 0.06). Barriers to hospice referral were not well documented by providers but lack of family support for home EOL care was a common reason patients declined hospice. Conclusions: ICI was associated with a higher rate of systemic treatment at EOL as compared to a historical chemotherapy cohort, although the rates of hospice referral and other outcomes were similar.
Predictive role of Vulnerable Elders Survey-13 screen tool for elder cancer patients in final oncology treatment plan.
Authors: Almugbel Fahad , Timilshina Narhari , AlQurini Naser , Jin Rana , Berger Arielle , Romanovsky Lindy , Puts Martine , Loucks Allison , Alibhai Shabbir M.H.
Published: May 2020

e24020

Background: The Vulnerable Elders Survey (VES-13) is one of several tools that can identify older patients who are vulnerable (if the score is ≥ 3 out of 10) and more likely to benefit from Comprehensive Geriatric Assessment (CGA) prior to cancer treatment. The optimal cutpoint of the VES-13 to identify those whose final oncologic treatment plan would change after CGA is unclear. We hypothesized that patients with high positive scores (7-10) will have a higher likelihood of a change in the final oncologic treatment plan compared to low positive patients (score 3-6). Methods: Retrospective review of a customized database of all patients seen for pre-treatment assessment (solid tumor and lymphoma) in the geriatric oncology clinic at the Princess Margaret Cancer Centre from June 2015 to June 2019. Various VES-13 score cutpoints were compared with the final treatment plan to identify those individuals whose treatment was modified after CGA. Area under the curve was calculated and subgroups of patients treated locally or systemically were also examined to determine if performance varied by type of patient. Results: 386 patients with mean age 81, 58% males were included. Gastrointestinal cancer was the most common site 31% and 60% were planned to receive curative treatment. The final treatment plan was modified in 50% with VES-13 scores 7-10, 46.7% with scores 3-6 and 26.8 % for scores < 3 (P = 0.002; Table). The optimal VES-13 cutoff was between 3-6 (C-statistics 0.57-0.59).The VES-13 performed similarly in those considering local treatment (surgery with/without radiation) vs. chemotherapy. Modified final treatment for local therapy with VES-13 scores < 3 was 11.4 % compared to 42.9% with scores ≥ 3 was 42.9% (p-value < 0.001), whereas for systemic therapy it was 32.4% and 62.5%, respectively (p-value = 0.002). Conclusions: Although high positive VES-13 scores (7-10) had slightly higher likelihood of having the final oncologic treatment plan modified, there was no strong advantage compared to the conventional cutpoint of 3 or higher. The VES-13 performed similarly in predicting treatment change after CGA for local and systemic treatment plans. Further studies are required to identify the optimal frailty screening tool and cutpoint. [Table: see text]
Enhancing safety of exercise for individuals with bone metastases: Screening recommendations developed through Delphi consensus process.
Authors: Campbell Kristin L. , Weller Sarah , Cormie Prue , Lane Kirstin N. , Rauw Jennifer Marie , Goulart Jennifer
Published: May 2020

e24042

Background: Exercise has been shown to improve physical function and quality of life in individuals with bone metastases. To facilitate better integration of exercise services into clinical care for these more complex patients, the purpose was to understand the current views of an expert panel on the appropriate exercise screening approach for adults with bone metastases. Methods: Physicians, physical therapists and exercise physiologists with clinical or research expertise in providing medical and/or exercise advice to individuals with bone metastases were identified. A 3-round modified online Delphi survey was used to establish a consensus, with a priori consensus set to 70%. Results: Response rates were 68% (73/107), 81% (59/73) and 97% (57/59) for each Delphi round. Key consensus points were: a) medical guidance (i.e. communication and medical information from a physician) is recommended prior to commencing structured exercise for all individuals with bone lesions (90% consensus) and is required when individuals present with bone pain, have received past medical treatment for bone pain, or have a history of disease-related fractures (90% consensus); b) the primary objective of exercise professionals for seeking medical guidance is to obtain medical information (e.g., bone scan reports) to guide clinical decision making for exercise prescription (93% consensus) and for bi-directional communication (i.e., for overall patient care and safety) (75% consensus) versus requiring a direct referral from a physician for liability coverage (39% consensus); c) the physician group that exercise professionals most commonly approach for medical guidance are medical oncologists (84% consensus) or radiation oncologists (63% consensus) compared to primary care providers (33% consensus), orthopedic surgeons (40% consensus) or physiatrists (16%); d) as part of pre-exercise screening by an exercise professional, information should be collected on the number, location and type of bone lesion(s), level of bone pain and any other bone-related symptom (100% consensus). Conclusions: This represents the current views of a range of physicians, physical therapists, exercise physiologists and researchers who provide medical and/or exercise advice to adults with bone metastases. These findings will inform the work of the International Bone Metastases Exercise Working Group to establish the first exercise guidelines for adults with bone metatases.
Self-reported memory problems in adult-onset cancer survivors in the United States with or without: Type 2 diabetes mellitus, hypertension and hyperlipidemia.
Authors: Thimothee Valerie , Kendall Alexis , Perez Ashley , Friar Elora , Rothman Catherine , Carpenteiri Francesca , Winters Paul , Robinson Temple , Jean-Pierre Pascal
Published: May 2020

e24062

Background: Cancer and chronic diseases (CD) are independent predictors of cognitive dysfunction, especially memory problems that can impact patients’ psychosocial functioning and quality of life. We examined the prevalence of memory problems in cancer patients with or without CD, including Type 2 Diabetes mellitus (DM), hypertension (HTN) and hyperlipidemia (HLD). Methods: We examined data from people who completed the US National Health and Nutrition Examination Survey from 2009 to 2016 to determine the prevalence of memory problems in cancer survivors vs. non-cancer survivors with and without a history of CD. Participants answered the ‘yes’ or ‘no’ question: “Are you limited in any way because of difficulty remembering or because you experience periods of confusion?” History of Cancer, DM, HTN and HLD were self-reported. We used Rao-Scott Modified Chi-Square Test (X2test) for cross-classified categorical data from complex sample survey. Age, sex, race-ethnicity, education, poverty, and general health were controlled using logistic regression. Results: The sample included 21813 adults, ³ 20 years old, and ≈52% female. There were 40% Whites, 22% Blacks, 25% Mexican American/Other Hispanics, and 13% other race/multi-racial. About 46% graduated high School/had a GED (21.2%) or completed less than high school (24.4%). Of those with cancer ( N= 2025), memory problems were associated with DM (17.72%; X2test, p= 0.003) and (HTN, 13.42%; X2test, p= 0.007), but not HLD (11.66%; X2test, p= 0.786). Of those without cancer, memory problems were associated with DM, HTN and HLD (all p< 0.0001). Prevalence of CD was much greater in cancer survivors with memory problems ( p< .05). Conclusions: Strategies to mitigate memory problems in cancer survivors should consider the implications of DM, HTN and HLD, particularly given the prevalence of these chronic morbidities in cancer populations.
Hypothyroidism and its impact on outcomes in head and neck cancer.
Authors: Srinivas Sujay , Noronha Vanita , Patil Vijay Maruti , Joshi Amit , Menon Nandini Sharrel , Prabhash Kumar
Published: May 2020

e24066

Background: Hypothyroidism is a known late side effect of chemo-radiation in head and neck cancer. Hypothyroidism has been known to be associated with improved outcomes in renal cell carcinoma. Whether such a phenomenon exists in head and neck cancer is unknown. Methods: We performed a phase 3 study evaluating the role of Nimotuzumab in head and neck squamous cell cancers (HNSCC). In this study adult HNSCC patients treated with Cisplatin and radiation were randomly assigned to receive Nimotuzumab or not. The data of this study has been utilized for this analysis. Hypothyroidism was defined as TSH level more than 4.95 U/L. The cumulative incidence of hypothyroidism and its impact on PFS (progression free survival), OS (overall survival) and loco-regional control (LRC) was evaluated using binary regression analysis. To study the impact of hypothyroidism in outcomes a landmark analysis was performed. Results: 176/536 patients analyzed developed hypothyroidism with a cumulative incidence of 33%. Hypothyroidism showed a favorable impact on PFS, OS and LRC. Median PFS was 19.5 months while median OS was 22.2 months in the euthyroid subgroup vs not reached (NR) for both in the hypothyroid subgroup. The respective hazard rates (HR) for PFS and OS was 0.37 (95% CI: 0.27 - 0.52) and 0.15 (95% CI: 0.11 - 0.23). The LRC was also better with its median duration being 39.2 months vs NR in the euthyroid and hypothyroid subgroups respectively; HR for LRC being 0.40 (95% CI: 0.28 - 0.58). Conclusions: Thus development of hypothyroidism is associated with improved outcomes in HNSCC in terms of LRC and survival.
Cancer survivors with multiple chronic conditions: A rising challenge—Trend analysis from National Health Interview Survey.
Authors: Jiang Changchuan , Wang Haowei , Wang Qian , Zheng Binbin , Shapiro Charles L.
Published: May 2020

e24089

Background: Cancer survivors are disproportionally influenced by chronic/comorbid diseases, which were linked to more psychological distress, increased healthcare service use, higher medical costs, adverse clinical outcomes, and financial hardship in cancer survivors. However, the trend in chronic diseases remains unknown among cancer survivors. Methods: We conducted a population-based study using serial samples of the National Health Interview Survey (NHIS) from 2002 through 2018. The outcomes include hypertension, diabetes, stroke, coronary artery disease (angina pectoris, coronary heart disease, heart attack), other heart diseases, COPD (emphysema, chronic bronchitis in the past 12 month), hepatitis, arthritis, morbid obesity (BMI > 40 or BMI > 35 with obesity-related diseases), asthma attack within 12 months, weak/failing kidney, any liver disease. We included adults who 1) have a history of cancer for except non-melanoma skin cancer; 2) report outcomes of diseases. Multiple chronic conditions(MCC) were defined as three or more non-cancer chronic conditions. Multivariable logistics regression was used to estimate the annual percent change(APC) in prevalence from 2002 to 2018, using SAS 9.4 and accounting for the design of NHIS. Results: 30728 adult cancer survivors and 485233 adults without a history of cancer were included in the final analysis. We found increasing prevalence in hypertension, diabetes, kidney disease, liver diseases and morbid obesity from 2002 to 2018, and decreasing prevalence in heart diseases, COPD, and hepatitis. The prevalence of MCC increased significantly in cancer survivors from 23.6% in 2002 to 29.6% in 2018 (APC 0.9%, p trend < 0.01). This was especially evident in younger patients aged 18 to 44 (APC 4.4%, p trend < 0.01) and African-American patients (APC 2.2%, p trend = 0.01). Conclusions: Our findings suggest that comorbid illnesses, especially MCC, have become an emerging public health burden for cancer survivors, which requires attention and more effective risk factors interventions. Future studies are needed to identify a better strategy to modify risk factors and prevent long term comorbidities for cancer survivors. It is also important to call for public health planning given severe chronic diseases burden for this rapid-growing but vulnerable community.
Association of pectoralis muscle area and survival outcomes after chemotherapy.
Authors: Gu Christina , Wiederin Jason , Jewett Patricia , Blaes Anne Hudson
Published: May 2020

e24094

Background: Chemotherapy use may be associated with muscle wasting, a marker of frailty that can predispose individuals to poor outcomes. We assessed the association between pre-treatment pectoralis muscle area and overall mortality following chemotherapy. Methods: We identified individuals diagnosed with breast cancer (N=221), lymphoma (N=216), or sarcoma (N=115) who received chemotherapy at the University of Minnesota Masonic Cancer Clinic and had CT scans prior to chemotherapy 2009-2014. Using CoreSlicer, right pectoral muscle area was measured at baseline and indexed to body surface (right pectoralis muscle area [cm2] / body surface [m2]) and divided into quartiles. Restricting to individuals who started chemotherapy within 6 months after their CT, we used cox regression (adjusted for age, sex, cancer type, stage, ever-smoking, BMI, and chemotherapy type) to assess associations between baseline muscle area and overall survival, testing for nonlinear effects using cubic splines. Results: 536 individuals (66% female) were identified who were treated with anthracyclines based chemotherapy (N=408), Trastuzumab (N=64), or both (N=64). Mean baseline muscle area was 14.9 (4.6) cm2 in females and 26.3 (9.3) cm2 in males. Median follow-up was 4.6 years. Larger baseline pectoralis muscle area (per m2 body surface) was associated with improved survival (adjusted model, overall effect, P=0.01), with some nonlinear effects (P=0.05). With muscle area (per m2 body surface) categorized as quartiles, individuals in the 3rd and 4th quartiles were at lower risk of dying (compared with people in the 1st quartile, hazard ratios 0.59 and 0.55 respectively, 95% CI range 0.35-0.90, P=0.01). There were no differences comparing the 4th vs the 3rd quartile (P=0.79), or the 2nd vs the 1st quartile (P=0.5). Conclusions: We found a protective association between larger right pectoral muscle size (relative to body surface) and overall survival after chemotherapy. There may be ceiling and threshold effects given evidence for nonlinear effects, since neither the 2nd vs. 1st quartile, nor the 4th vs. 3rd quartile comparisons in the categorical model were significant. Hazard ratios and confidence intervals of overall mortality by pectoral muscle area at baseline indexed to body surface, N=536, 2009-14. [Table: see text]
Trajectories of sexual dysfunction and its risk factors in women with gynecologic cancer across radiation therapy and healthy controls.
Authors: Bai Jinbing , Tsementzi Despina , Patel Pretesh R. , Shelton Joseph W , Dolan Mary , Arluck Jessica , Bruner Deborah
Published: May 2020

e24097

Background: Women with gynecological cancer (GynCa) reported an increased risk for acute and long-term sexual dysfunction across cancer treatments, especially radiation therapy (RT). However, limited data exist on the course of sexual dysfunction across RT and its risk factors are unknown. This study sought to characterize women’s sexual dysfunction trajectories and identified risk factors of persistent sexual dysfunction. Methods: Using a longitudinal study design, patient-reported sexual dysfunction, demographic and clinical data were collected. Women receiving RT for GynCa older than 18 years or age, race, and BMI matched healthy controls were enrolled. Female Sexual Function Index (FSFI) was used to assess women’s sexual dysfunction. Patients completed all the questionnaires pre-RT, at the end of RT, 6- and 12-month post-RT. Group-based trajectory modeling was used to identify trajectories of sexual dysfunction and risk factors of persistent sexual dysfunction. Results: Eighty-two patients were analyzed, including 36 GynCa patients receiving RT and 46 healthy post-menopausal women, comprising of 33 Blacks, 44 Whites, and 5 others. Three trajectory groups of sexual dysfunction (total FSFI score) were identified: low risk (17.4%), moderate risk (12.3%), and high risk (70.4%). All three trajectory groups were significantly different from each other (p<0.01). Similarly, three trajectories were identified for each of six FSFI domains: desire (low [6.3%], moderate [62.5%], high [31.2%], p<0.01); arousal (low [38.1%], moderate [46.4%], high [15.4%], p<0.01); lubrication (low [49.7%], moderate [44.6%], high [5.7%], p<0.01); orgasm (low [43.8%], moderate [31.3%], high [24.9%], p<0.01); pain (low [25.5%], moderate [64.2%], high [10.3%], p<0.01); and satisfaction (low [8.3%], moderate [61.4%], high [30.3%], p<0.01). Risk factors of sexual dysfunction were high pH (p=0.007) and without chemotherapy (p=0.019). Young women had more arousal (p=0.011); high education level was associated with high arousal (p=0.039); low pH was associated with high arousal (p=0.018) and orgasm (p=0.036). No risk factors were found for desire and satisfaction domains. BMI, surgery, and study cohort (cancer vs healthy) were not predictors of sexual dysfunction trajectories. Conclusions: This study identified three trajectories of sexual dysfunction. Low education, high pH, no chemotherapy, and elder women were risk factors of severe sexual dysfunction. Sexual dysfunction interventions should address these risk factors.
Violence and chronic pain in cancer patients in northeastern Mexico.
Authors: Alcorta-Garza Adelina , Alcorta-Nuñez Fernando , Alcorta-Garza Antonia Gloria , Gonzalez Guerrero Juan Francisco , Gonzalez-Alcorta Celia Beatriz , Montiel-Labastida Jan Alejandro , Garza-Rodriguez Maria Lourdes , Vidal-Gutiérrez Oscar ,   Adelina Alcorta-Garza
Published: May 2020

e24113

Background: Chronic cancer pain generates fear and anguish in cancer patients. It is suffered by 64% of patients with metastatic or terminal disease, 59% of patients in early and intermediate stages, and 33% of patients cured from cancer. They require a psychosocial support network. This network has been proposed as an essential tool to reduce the negative impact of the symptoms and psychosocial implications of cancer on the quality of life of patients. Patients with dysfunctional family networks can add to the pain of suffering cancer when they suffered or suffer violence. Cancer and pain test all personal resources and the patient's support network where family functioning is capital for quality of life. Methods: Descriptive, comparative and correlational study. A sample was taken for convenience with the prior consent of the patients who attend the outpatient clinic of the Pain Clinic of the Oncology Service, of the University Center Against Cancer of the University Hospital “Dr. José Eleuterio González” in Nuevo León. The questionnaires were applied during a session of 25 to 30 minutes. It was requested to answer the scales to assess the level of intra-family functioning, intra-family violence, quality of life, measuring psychosocial and health variables; as well as for the detection of the type and quality of psychosocial support perceived by the subjects. Results: A total of 207 research subjects were included in the study, the average age was 49 years of age (minimum 12, maximum 81 years of age), 23% men and 77% women. Marital status: married 52%, home-based 63%; monthly income less than $120 USD (n = 75, 37%). The quality of life index and chronic cancer pain had a high linear correlation with the variables of family violence, psychosocial support, family functioning, somatic symptoms, among other variables studied. Fatigue was the symptom most frequently associated with the decrease in the quality of life index. Conclusions: The satisfaction of perceived social support is a factor associated with the quality of life in patients with chronic cancer pain, however, the number of caregivers is not. There was no relationship between the size of the network and satisfaction with it. Also, the symptoms associated with chronic cancer pain affect the quality of life, identity, social functionality and roles, which in turn impact the quality of life perceived by the patient. This study supports our comprehensive intervention programs and new protocols to promote the quality of life of cancer patients.