bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune checkpoint inhibition-related colitis: Correlation between ulcers and need for infliximab.
Authors: Geukes Foppen Marnix Heimen , Rozeman Elisa A. , van Wilpe Sandra , Postma Cindy , Snaebjornsson Petur , Van Thienen Johannes V. , van Leerdam Monique Esther , van den Heuvel Michel M , Blank Christian U. , van Dieren Jolanda , Haanen John B. A. G.
Published: September 2018

e21062

Background: Immune checkpoint inhibition has improved survival of patients with several types of advanced cancer. With these new treatments previously unseen adverse events (AE) have become relevant. Considering the fact that most of these immune related AEs can be reversed when identified early and treated adequately, the need for updated algorithms is crucial. Colitis is one of the most severe AEs upon anti-CTLA-4 (e.g. ipilimumab) monotherapy or combination therapies. Severe colitis with deep ulcerations is associated with life-threatening complications such as perforation. Therefore, early recognition and treatment is warranted. Anti-TNF therapy (infliximab) can resolve colitis fast. We sought to identify endoscopic features that indicate the need for early treatment with infliximab. Methods: We retrospectively analyzed all patients who developed diarrhea upon checkpoint inhibition. Only patients undergoing endoscopy were included. All patients were treated at the NKI between August 2010 and March 2016 for either metastatic melanoma or non-small cell lung cancer. Results: A total of 89 patients underwent an endoscopy due to immune related diarrhea (irDiarrhea). Patients were treated with either monotherapy anti-CTLA-4, anti-PD-(L)1, a combination of both, or the combination of anti-CTLA-4 and radiofrequency ablation. Median age was 58 years (range 30-88) and 54% of patients were female. A colonoscopy was performed in 64 (72%) patients and a sigmoidoscopy in 25 (28%) patients. Ulcers were seen during 29 endoscopies (32%). In 18 endoscopies (20%) there were ≤ 10 ulcers and in 11 endoscopies (12%) > 10. Of all patients that had ulcers at endoscopy 23 (79%) required additional infliximab treatment for corticosteroid refractory colitis, while only 25 (42%) of patients without ulcers required additional infliximab ( p= 0.001). Conclusions: Patients with ulcerative irColitis require twice as often infliximab in addition to corticosteroids. Early treatment with infliximab may be indicated in ulcerative irColitis. Treatment based on endoscopic features makes colonoscopy an important diagnostic tool in irDiarrhea. Prospective analysis of endoscopy-driven management of irColitis is warranted.
In-hospital cardiac arrest among patients with malignancy.
Authors: Rosen Sheri , Eng Kevin , Yang Jenny , Tyagi Sanjeev , Odish Mazen , Sell Rebecca , Beitler Jeremy
Published: September 2018

e21583

Background: Malignancy is generally considered a poor prognosticator for in-hospital cardiopulmonary arrest. Recent studies have shown that overall survival in those with localized disease and fewer than two comorbidities approximates the general population, likely reflective of advances in cancer treatment and more selective use of cardiopulmonary resuscitation. The present study was conducted to evaluate whether malignancy is an independent risk factor for death before discharge following in-hospital cardiopulmonary arrest. Methods: This single-center retrospective study included consecutive in-hospital cardiac arrests for whom cardiopulmonary resuscitation was attempted between 2011-2015. Patients were identified from an inpatient cardiac arrest registry and excluded if the arrest occurred in the operating room or emergency department prior to admission. Data related to each patient’s oncologic history was obtained via manual chart review by physician investigators. The primary outcome was survival to discharge among patients according to malignancy status. Results: Over the five-year study, 532 patients experienced in-hospital arrest and met inclusion criteria. Fifteen percent (n = 81) had a known cancer diagnosis at the time of arrest; 9% of arrests (n = 46) had a cancer that was considered active (not in remission). One-fourth of all cancer diagnoses at time of arrest were hematologic malignancies. Overall post-arrest survival to discharge was 34%. Survival did not differ significantly for patients with versus without current or prior malignancy (OR 0.69, 95% CI 0.41-1.18; p = 0.17), nor with active malignancy at time of arrest (OR 0.52; 95% CI 0.25-1.07; p = 0.08). The subgroup of patients with hematologic malignancy had significantly lower survival (OR 0.21, 95% CI 0.05-0.91; p = 0.04). Conclusions: Malignancy was not associated with decreased survival to hospital discharge among patients experiencing in-hospital arrest for whom resuscitation was attempted.
Phase II feasibility study of rekindle: An online psychosexual intervention for cancer survivors and/or their partners.
Authors: Lawsin Catalina Rosario , McGeechan Kevin , Williams Douglas O , Butow Phyllis , Juraskova Ilona , Hobbs Kim , Boyle Frances M. , Kay Judy , Miller Annie , Dhillon Haryana M.
Published: September 2018

e21597

Background: Changes to sexual wellbeing can negatively impact long-term quality of life for cancer patients and their partners. Rekindle is an online intervention aimed to provide accessible and tailored psychosexual support to cancer survivors. This study aimed to assessed the feasibility of delivering psychosexual support via Rekindleto cancer survivors and partners who self-report unmet sexual concerns. Methods: This phase II feasibility study, recruited Australian adult cancer survivors who had completed primary therapy > 6 months earlier and/or their partners. Participants were randomized 1:2:1 ratio to either: i) wait list control (WC); ii) Rekindle (10-week online intervention addressing psychoeducational sexual communication and function) (Int); iii) Rekindle Plus ( Rekindleintervention plus three support telephone calls) (Int+). Intervention ran for 10 weeks, after which WC group had access to Int. Participants completed assessments at baseline (T1), intervention end/10 weeks (T2), and six months (T3). The primary feasibility endpoint was the proportion of participants completing prescribed intervention modules. Results: Nov 2015-Dec 2016, 100 participants were randomized: WC: 19, Int: 54, Int+: 27. Baseline characteristics were matched across groups. 57% were male and 91% cancer survivors; 46% had prostate and 23% breast cancer. Participants were prescribed a mean of 6.5 out of 7 modules based on self-reported unmet sexual needs. They completed mean of 1.9 (Int) and 2.5 (Int+) modules with 30% (Int) and 38% (Int+) completed within 10 weeks. A high proportion of users (94%, 100%) commenced Module 1 (Foundations). The largest drop-out between occurred between Modules 1 and 2. Once started, the majority of participants completed each module (76-100%). The mean number of days taken to complete each module varied (4-14 days). Factors impacting engagement with the intervention will also be reported. Conclusions: This phase II study has demonstrated: a need for psychosexual support amongst cancer survivors, that it is feasible to recruit them into an online sexual support study, and to deliver online psychoeducational content for sexual concerns. Clinical trial information: ACTRN12614001245684.
Measuring concordance with head and neck cancer survivorship algorithms.
Authors: Rodriguez Maria Alma , Palos Guadalupe R. , Gilmore Katherine Ramsey , Chapman Patricia , Lewis-Patterson Paula A.
Published: September 2018

e21602

Background: We developed institutional algorithms for cancer survivors that are site specific. However, little data exists regarding concordance with these clinical management tools. Our aim was to evaluate concordance rates with our Head and Neck (H/N) survivorship algorithms. Methods: We reviewed electronic health records (EHR) of patients seen in the H/N Survivorship Clinic between 9/01/2011 and 8/31/2014. Eligibility included: diagnosis of primary head and neck cancer, ≥ 18 years of age, no active disease, and alive at time of abstraction. Data were collected at baseline (V1) and visits 9-15 months after prior visits (V2 and V3). Data were obtained from tumor registry, a departmental database and the EHR. Twelve data elements were grouped as: 1) lab/diagnostic tests, 2) physical and psychological late effects, and 3) history and physical exams. Concordance rate (%) for each element was defined as a clinical action or recommendation aligned to the standards outlined in the H/N algorithms. Descriptive statistics were used to summarize clinical, demographic, and concordance rates. Results: Included in this analysis were patients with primary H/N malignancies of oropharynx, oral cavity, larynx, and hypopharynx, and who had completed 3 visits (V1-3). 53 patients were evaluable for concordance analyses. Compliance ranged from 55% to 100%, with lowest rates for: CT scans (55.6%), distress screening (75.5%), T4/TSH level (78.4%) and laryngoscopy (79.2%). Highest rates were noted for full physical exam (100%), chest x-ray (97.5%), dental exam (95.9%), and dysphagia evaluation (95.1%). Assessments for lymphedema and xerostomia were similar (91.8%). Conclusions: High compliance ( > 90%) occurred when elements of the algorithm relied on the clinician’s assessment, whereas lower levels of compliance were seen with elements that required orders (CTs and labs), or reliance on others’ actions (i.e. distress screening by nursing). Concordance can be improved using best practice advisories in the EHR to remind providers of orders, and by fostering strong inter-professional communication on the elements of care.
Examination of factors that influence use of extended adjuvant endocrine therapy (ET).
Authors: Kadakia Kunal C. , Kidwell Kelley M. , Barton Debra L. , Griggs Jennifer J. , Henry Norah Lynn
Published: September 2018

e21618

Background: Extending adjuvant ET from 5 to 10 years has been shown to improve outcomes; however, limited data are known about if and why women pursue extended ET. The primary objective was to estimate the proportion of women who were willing to receive extended ET and secondarily, to determine what factors were associated with this decision. Methods: 133 women on ET for 3-5 years who had not made a decision on extended ET completed a survey about willingness to continue ET, quality-of-life (Functional Assessment of Cancer Therapy-Endocrine Subscale [FACT-ES]), and beliefs about medicines (Beliefs about Medicines Questionnaire Specific [BMQ-S]). BMQ-S assesses patients need for a treatment (necessity beliefs) and concerns about its adverse effects (AEs). The primary outcome, responses to "If in meeting with your doctor, he or she recommends continuing hormonal therapy for longer than 5 years (up to 10 years), how willing ("Not at all" to "Extremely") would you be to continue taking your current hormonal therapy?" was analyzed descriptively. Logistic regression tested for associations between clinical factors (age, stage, chemotherapy), FACT-ES, BMQ-S, and the primary outcome. Results: Most women (112, 85%, 95% confidence interval, CI, 78-91%) were "Moderately" to "Extremely" likely to pursue extended ET. On univariate analysis, younger age (<49 vs ≥50), lower total and social well-being on FACT-ES, and lower necessity and higher concerns on BMQ-S were associated with less willingness to pursue extended ET. Neither stage nor prior chemotherapy was associated with this decision. On multivariable analysis, age and FACT-ES were not associated with this decision (odds ratio, OR 1.03, 95% CI 0.96-1.09, p=0.41; OR 1.01, 95% CI 0.98-1.05, p=0.49). Greater patient perception of necessity of ET compared to concern for AEs was the only independent factor associated with willingness to pursue extended ET (BMQ-S OR 1.34, 95% CI 1.15-1.57, p=0.0005). Conclusions: Most women are likely to purse extended ET if recommended by their physician. Patient decision-making appears to be largely influenced by beliefs of medicines rather than breast cancer-specific clinical factors and should be considered when counseling patients on extended ET.
Phase II study of efficacy of bevacizumab plus chemotherapy in management of malignant pleural effusion (MPE) in non-squamous non-small cell lung cancer (NSCLC) patients with MPE unsuccessfully controlled by tube drainage or pleurodesis (North East Japan Study Group Trial NEJ-013B-2).
Authors: Noro Rintaro , Kobayashi Kunihiko , Usuki Jiro , Hosomi Yukio , Nishitsuji Masaru , Okamoto Hiroaki , Hino Mitsunori , Hagiwara Koichi , Miyanaga Akihiko , Seike Masahiro , Kubota Kaoru , Gemma Akihiko
Published: September 2018

e21660

Background: Prospective and retrospective studies on intrapleural therapy of malignant pleural effusion (MPE) have reported that the success rate for controlling pleural effusion was 50–70% at 2.5 months, and that the median post-pleurodesis survival time was 6-9 months. When pleurodesis is unsuccessful, and the lung is not fully expanded after drainage, the patients cannot receive effective chemotherapy. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Here, a multicenter phase II trial was conducted to evaluate bevacizumab therapy in non-squamous non-small cell lung carcinoma patients with unsuccessful management of MPE. Methods: Non-squamous NSCLC patients with MPE who had received unsuccessful tube drainage or pleurodesis received chemotherapy with bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was Pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE for 8 weeks. The secondary endpoint was pleural Progression-free survival (PPFS), defined as PFS without reaccumulation of MPE. Results: Fifteen of 20 patients entered received a median of 4 cycles of carboplatin plus paclitaxel or pemetrexed including maintenance therapy with bevacizumab. The PECR was 80% of treated patients (95% CI: 78-82%). PPFS was 16.6 months (95% CI: 11.46-21.80 months). The response rate (RR) and disease control rate (DCR) were 45% (95% CI: 39.6-50.4%), and 80% (95% CI: 78.0-82.0 %), respectively, and the median PFS and overall survival (OS) were 9.8 months (95% CI: 4.38-15.28 months) and 19.6 months (95% CI: 4.38-15.28 months), respectively. Toxicities of grade ≥3 included neutropenia (50.0%), thrombocytopenia (10.0%), proteinuria (10.0%), hypertension (2.0%), pulmonary embolism (5%). Conclusions: The combination of bevacizumab with chemotherapy demonstrated efficacy with acceptable toxicities in controlling MPE in patients with non-squamous NSCLC whose MPE was unsuccessfully controlled by tube drainage or pleurodesis.
In vivo changes in the cutaneous antioxidant status during sorafenib, sunitinib and capecitabine treatment.
Authors: Jung Sora , Lademann Juergen , Sehouli Jalid , Darvin Maxim E. , Fuss Harald
Published: September 2018

e21664

Background: A potential pathomechanism for doxorubicin-associated hand-foot syndrome (HFS) was shown based in particular on radical formation in the skin. Topically applied antioxidants (AO) have a therapeutic effect on HFS. Here, radical formation of orally administered sorafenib (Nexavar), sunitinib (Sutent) and capecitabine (Xeloda) was investigated. Methods: 26 patients were included in the study in total, including 13 patients receiving capecitabine (2-4 g/day), 7 patients receiving sunitinib (25-50 mg/day) and 6 patients sorafenib (400 mg/day). Cutaneous carotenoids serving as marker substance of the AO status of the epidermis were measured in vivo using a miniaturized measuring system based on multiple spatially resolved reflectance spectroscopy. Measurements were performed 1 day before the first oral administration and on the 10thday during the first cycle of chemotherapy including an assessment of HFS skin lesions. Results: The mean AO status in capecitabine patients showed an insignificant decrease from 4.09±0.25 to 4±0.25 and in sunitinib patients an insignificant increase from 4.32±0.36 to 4.82±0.52. The AO status in patients treated with sorafenib was shown to increase significantly from 4.77±0.32 to 5.20±0.33, p = 0.028, along with an enhanced subjective vitality and well-being. Overall 3 patients, 1 in each treatment group, developed HFS grade I during the observational period of the first cycle. Conclusions: Sorafenib-, sunitinib- and capecitabine-associated HFS might not occur due to radical formation only, but due to different underlying pathomechanisms. As an AO decay was observed previously after intravenous, but not after oral administration of chemotherapeutics, the metabolisation of these agents after oral and intravenous intake might influence HFS development. Therefore, the application of topical AO might not have preventive effects for these orally applied chemotherapeutics, as shown for capecitabine previously. As therapeutic effects of topically applied AO in case of capecitabine and sorafenib induced HFS have been reported, it seems that although the pathomechanisms are different, radical formation can occur once HFS lesions have developed.
Patient preference for receiving information about long-term symptoms.
Authors: Bennett Antonia Vickery , Eberle Carolyn E. , Schleicher Stephen Matthew , Aviki Emeline , Patil Sujata , Basch Ethan M. , Sloan Jeff A. , Blinder Victoria Susana
Published: September 2018

e21681

Background: Maintaining quality of life with minimal symptoms is an important goal of cancer treatment. We surveyed patients undergoing cancer treatment about their preferences for information about the long-term symptom burden associated with their current treatment. Methods: Patients undergoing active cancer treatment were enrolled at two large cancer centers from 1/2014 to 7/2015. At the time of enrollment patients reported their household income, employment, performance status and their agreement with the statement, “It would be useful to know the percentage of patients having persistent symptoms more than a year after getting the same treatment I am getting.” Treatment intention (curative vs. palliative) was reported by the treating oncologist. Results: 196 patients completed the survey. The mean age was 55.7 (range 20-80); 54% were female, 69% were white, and 60% were receiving palliative treatment. The majority (83%) of patients either strongly agreed or somewhat agreed that it would be helpful to have information about future symptoms. In univariable analyses, this preference did not significantly differ based on patient-reported performance status, sex, age, treatment intent, race, or household income. Using a more stringent criterion to dichotomize the outcome, 59% of participants strongly agreed that it would be helpful to have information about future symptoms. Patients undergoing treatment with curative intent were significantly more likely to strongly agree (72% vs. 51%, p = 0.0035). In a multivariable analysis adjusting for age, sex, income level, employment status, and patient-reported performance status, participants undergoing curative versus palliative treatment had 3.1 times the odds (95% CI 1.47-6.65) of strongly agreeing. Conclusions: The majority of patients undergoing cancer treatment wanted to know what symptoms to expect in the future, and this was independent of patient demographics. Patients undergoing treatment with curative intent are significantly more likely to want this information than patients undergoing palliative treatment. Symptom data collected through research studies and registries should be summarized by treatment and other key predictors and made available to patients.
Effects of plantar reflexology on sleep and quality of life in patients with breast cancer undergoing chemotherapy and hormonal therapies.
Authors: Magno Stefano , Cappai Elena , Dentale Francesco , Carnevale Stefania , Belella Daniela , Scaldaferri Assunta , Filippone Alessio , Masetti Riccardo
Published: September 2018

e21697

Background: In the last decade, several studies have shown the role that integrative therapies (e.g. acupuncture, herbal medicine, body-mind practices) can play to relieve symptoms related to cancer and its mainstream treatment. However, conclusive evidence about the value of Plantar Reflexology (PR) on side effects management in breast cancer patients is still lacking. Methods: Forty-four breast cancer patients, treated at Catholic University Hospital’s Breast Unit, were enrolled and invited to complete the Pittsburgh Sleep Quality Index (PSQI) and the Quality of Life index (QL). Afterward, they were randomized into two groups: 23 patients were treated with 6 weekly sessions of PR (1 hour each) conducted by a specialist (experimental arm), while the other 21 underwent standard medical treatment alone (control arm). At the end of treatment sessions, PSQI and QL were re-administered in both groups. Results: A Multivariate Analysis of Covariance (MANCOVA) was conducted, including the participation to experimental vs. control group as an independent variable, PSQI and QL post-test scores as dependent variables, PSQI and QL pre-test scores and patients’ age as covariates. Results showed that PR improved significantly the quality of sleep [F(1, 39) = 4.94, p < .05)], but no significant effects emerged on the quality of life. A further MANCOVA, conducted on the subscales of the PSQI, showed significant mean differences in sleep disturbances [F(1, 34) = 4.38, p < .05), sleep latency [F(1, 34) = 4.88, p < .05) and sleep quality [F(1, 34) = 6.92, p < .05) in favor of the experimental group. Conclusions: Results suggest that PR may relieve sleep difficulties typically linked to mainstream therapies for breast cancer. No effects of PR emerged for patients’ quality of life, although the small sample tested does not allow to draw any definitive conclusion. These promising results encourage further investigations about the beneficial role of PR. In our initial experience, PR appears as easy, well-tolerated and safe procedure, that can play a role in the management of symptoms that are poorly controlled by conventional pharmacological treatments.
Evaluation of art therapy on mood, anxiety, and pain levels in patients with cancer undergoing chemotherapy treatment.
Authors: Doll Marie , Roshon Steven Gale , Stone Elizabeth Rodriguez , Butler Robert Sam
Published: September 2018

e21713

Background: Art therapy is a mental health modality that uses art-making to improve the physical, mental, and emotional wellbeing of individuals for a variety of purposes. The primary purpose of the trial is to assess the effect of art therapy on cancer patients' mood, anxiety, and pain levels. Secondary endpoints include exploring difference in response to art therapy by specific patient characteristics. Methods: Trial enrolled 50 cancer patients receiving chemotherapy. They participated in an hour long art therapy session with Art Therapist. Patients completed four visual analog scales (VAS) at three different time points: pre-treatment, post treatment (immediately after session) and 48-72 hours after session. Primary end points are pre and post session changes in the VAS for distress, depression, anxiety and pain. Secondary endpoints include differences in VAS scores by ethnic groups (Hispanic vs non-Hispanic), race (white vs non-white), age, gender, and marital status. Analysis was performed using repeated measures, mixed models, and pairwise means comparisons for the four measurements using the Tukey-Kramer adjustments for multiple comparisons. Results: Study revealed a statistically significant difference between pre treatment and post treatment as well as pre-treatment and follow up across distress, depression, anxiety and pain. There was no statistically significant difference between post treatment and follow up. The only significant correlation seen among patient characteristics was that Hispanic patients had higher depression scores at all time points vs non-Hispanics. Conclusions: Art therapy improved mood, anxiety and pain among all patients. Benefits were seen immediately after session and persisted at least 48-72 hours across all groups equally. Hispanic patients had higher depression scores compared to non-Hispanics. Clinical trial information: NCT02659345. [Table: see text]
Benign metastasizing leiomyoma (BML): A retrospective case series analysis of 8 patients (pts).
Authors: Colia Vittoria , Dei Tos Angelo Paolo , Fumagalli Elena , Bertulli Rossella , Lorusso Domenica , Raspagliesi Francesco , Morosi Carlo , Carcangiu Maria Luisa , Casali Paolo Giovanni , Sanfilippo Roberta
Published: September 2018

e22525

Background: BML is a rare entity marked by the presence of lung lesions in women with a history of surgery for a benign leiomyoma of the uterus. Optimal treatment strategy for BML is poorly defined. We report on the activity of systemic therapy in a retrospective series of pts with BML. Methods: Cases diagnosed with BML from June 1993 to January 2017 at Istituto Nazionale Tumori, Milan, were reviewed. Results: Eight pts were identified, with a median age of 43 yrs. Estrogen and progesteron receptors were positive in all cases. All pts underwent surgery (3 hysterectomy, 2 myomectomy, 2 hysteroannessiectomy and 1 left ovariectomy) for suspected uterine leiomyoma (1 leg; 1 thigh); 2 pts had concomitant lung disease. 8 pts developed lung metastases and 2 had also limb metastases. 2 pts underwent lung metastasectomy, followed by watchful waiting with CT every 6 mos and were disease-free at their last follow up after 132 mos and 84 mos from diagnosis. 6 pts received systemic therapy for progressing advanced disease (1-6 lines). Among 6 pts treated, 2 were in fertility age and underwent ovary-sparing hysterectomy, receiving GnRH agonist with 1 PR lasting 96 mos and 1 SD lasting 38 mos; 2 pts received an aromatase inhibitor with 1 PR lasting 24 mos and 1 SD lasting 12 mos; 2 pts received oral estrogens with 1 PR lasting 39 mos and 1 SD lasting 2 mos; 1 pt received oral progestins with a PR lasting 12 mos; 3 patients received antracyclin +/- ifosfamide obtaining 2 PR after 3 cycles (cys) and 1 SD after 3 cys lasting 6 mos; 1 pt received high-dose ifosfamide with a PR after 5 cys; 1 pt received ifosfamide+dacarbazine obtaining a CR after 6 cys; 2 pts received gemcitabine with 1 PR after 3 cys and 1 SD after 2 cys lasting 6 mos; 1 pt received oral etoposide with a PR lasting 21 mos; 1 pt received sorafenib with a SD lasting 6 mos; 1 pt received everolimus with a PR lasting 57 mos. In this case, everolimus was discontinued due to lung toxicity. No pts progressed during treatment. At a median follow-up of 55 mos, 6 pts are alive, while 2 are dead of disease. Conclusions: In a series of 8 pts, we confirm the activity of hormonal treatment in BML. mTOR inihibitors or chemotherapy also show to be active.
Carcinosarcoma: A single centre experience and population based study.
Authors: Bhattacharya Gaurav , Aljawi Ghufran Abdulghaffar , Bang Andrew , El Sayed Samy
Published: September 2018

e22526

Background: Carcinosarcomas, consisting of biphasic morphological patterns including both epithelial and sarcomatoid components, are rare malignant tumours. We highlight the incidence and outcomes of this unique disease at our large cancer referral centre. Methods: A retrospective review consisting of carcinosarcoma patients over a 10 years span from 1/1/2005 to 1/1/2015 with follow up data through to 2/2017 to ensure at least 2 years of post-treatment data collection by purveying Electronic Medical Records, paper charts and where required, communication with peripheral facilities, was conducted. Inclusion and exclusion criteria were histologic confirmation and age < 18 years respectively. A comprehensive literature review was also conducted to identify current outcomes trends. Results: Seventy patients meeting selection criteria were identified out of a total of 968 entries involving all soft tissue tumors. Incidence was mainly of gynecological origin (88.5%), in female patients (92.9%) and chiefly Grade 3 disease. Commonest presenting symptom was vaginal bleeding (54.3%). A majority received surgery (90.0%) primarily with a curative intent. 54.3% of the patients received chemotherapy and 51.4% received radiation; both largely in an adjuvant setting. Commonest treatment regimen was Carboplatin/Paclitaxel (73.7%) with a median of 6 cycles provided. Overall, 11 patients had a component of local failure with the latest failure recorded at 13.3 months. Conclusions: Treatment outcomes for carcinosarcoma over the years remain comparable to published results although there remains room for improvement. More research is required to identify strategies for improvement in both locoregional and systemic control. [Table: see text]
Comparison of tumor mutational burden (TMB) across tumor tissue and circulating tumor DNA (ctDNA).
Authors: Davis Andrew A. , Chae Young Kwang , Agte Sarita , Pan Alan , Simon Nicholas I , Taxter Timothy J. , Behdad Amir , Carneiro Benedito A. , Cristofanilli Massimo , Giles Francis J.
Published: September 2018

e23028

Background: TMB is a potential biomarker for response to checkpoint blockade. Prior studies have associated tissue TMB with genomic instability and neoantigen binding sites for activated effector T cells. The goal of our study was to compare TMB in patients with paired next-generation sequencing (NGS) tests from tissue and ctDNA. Methods: Ninety-seven patients with NSCLC (N=53), breast cancer (N=34), and other solid tumors (N=10) with paired tissue (FoundationOne) and ctDNA (Guardant360, currently not clinically indicated for TMB) were examined retrospectively. Insufficient samples were eliminated (e.g., poor tissue quality or no mutations detected). TMB was compared using variants of unknown significance and synonymous mutations both with (N=74) and without potentially functional/driver variants (N=55). Results: Paired samples were compared using both continuous and binary TMB classifications (Table 1). TMB scores were significantly different using both comparisons (paired t-test, p<0.05). In addition, correlation coefficients between the two assays were low (Pearson Correlation, r=0.24-0.33). No significant differences were found based on timeframe between biopsies. Conclusions: This study demonstrated a lack of concordance between TMB for tissue and ctDNA in paired samples. Potential reasons include differences in sequencing length (~0.79-1.1 million bp for tissue vs. 78,000-138,000 bp for ctDNA), mutation detection, and methods of determining TMB. Future studies are warranted to determine whether ctDNA TMB can predict response to immunotherapy. [Table: see text]
The role of atypical chemokine receptor-1 in breast cancer immune response.
Authors: Martini Rachel , Nikolinakos Petros , Hodgson Jamie , Jenkins Brittany , Davis Melissa
Published: September 2018

e23072

Background: Interactions between chemokines and their receptors can regulate anti-tumor response by influencing the migration of immune cells. Atypical Chemokine Receptor 1 (ACKR1/DARC), a genetically diverse transmembrane GPCR, acts as a decoy receptor for a variety of CXC and CC chemokines, including those with pro-malignant and pro-inflammatory effects, such as CCL2 and CXCL8 . The purpose of this study is to determine if the migration of tumor-associated immune cells is unique based on epithelial ACKR1 expression on breast cancer cells, and if this association is correlated to an increase in pro-malignant chemokines, survival, or race. Methods: Immunohistochemistry techniques were used to determine expression of ACKR1 on primary breast tumors, along with T-cells, B-cells, dendritic cells, and macrophages. Concentrations of pro-inflammatory chemokines in circulation were determined using a Luminex-based immunoassay. In silco analyses were performed to determine associations between ACKR1 tumor status, race, and survival. Finally, using human breast cancer cell lines and immunofluorescence techniques, co-localization between ACKR1 and pro-inflammatory chemokines was investigated. Results: Results from these tests indicate that there is differential infiltration of immune cell types in tumors expressing ACKR1, , which were not detected in ACKR1 negative tumors. Significantly increased circulating CCL2 and CXCL8 chemokine levels we also determined to be positively correlated with ACKR1 expression in primary breast tumors. Survival analyses showed a significantly increased relapse free survival in patients having tumors with high ACKR1 expression, while investigations into racial differences revealed a significant race effect, with Caucasians having higher ACKR1 levels on their tumors than African-Americans. Finally, co-localization between ACKR1 with CCL2 and CXCL8 is observed in cultured human breast cancer cells. Conclusions: tumors positively expressing ACKR1 to have a more favorable prognosis suggest that a role of ACKR1 on breast tumor cells is to sequester pro-inflammatory chemokines in the tumor microenvironment, recruiting a distinct subset of tumor-associated immune cells.
Detection of EGFR mutations in NSCLC patients in clinical practice: Comparison between cobas and Scorpion ARMS method.
Authors: Takano Natsuki , Kitazono Satoru , Ariyasu Ryo , Koyama Junji , Saiki Masafumi , Sonoda Tomoaki , Kawashima Yosuke , Oguri Tomoyo , Nishikawa Shingo , Yanagitani Noriko , Ohyanagi Fumiyoshi , Horiike Atsushi , Horai Takeshi , Nishio Makoto
Published: September 2018

e23101

Background: Epidermal growth factor receptor (EGFR) mutation is the most important factor for determining the treatment strategy for non-small-cell lung cancers (NSCLCs). Currently, two methods (cobas and Scorpion ARMS) have been approved as companion diagnostics for using EGFR tyrosine kinase inhibitor (TKI). Although there are some differences in the spectrums and sensitivities for detecting EGFRmutations such as exon 19 deletions (ex19del), L858R and T790M mutations, the extent of the differences affecting clinical practice is unclear. Methods: All patients with NSCLC who underwent EGFR mutation tests and treated at our hospital from February 2014 to February 2016 were enrolled. To detect EGFR mutations, the Scorpion ARMS (S) method was used from 2014 to 2015 and thecobasEGFR Mutation Test (C) from 2015 to 2016. We retrospectively investigated the detection rate of each EGFRmutation type and compared the rates between the two methods. Results: A total of 1,287 patients were enrolled. To detect EGFR mutations, 627 patients were tested by the S method and 660 by the C method, respectively. Of 1287 patients, 910 patients underwent initial biopsy, whereas 121 patients underwent re-biopsy after EGFR-TKI failure. EGFRmutations were detected in 130 of 418 (31.1%) patients and 153 of 492 (31.1%) patients by the S and C methods, respectively in the initial biopsy (P = 0.982). However, the detection rate of ex19del was slightly lower in the S method (12.6%) than in the C method (16.3%) (P = 0.105). Conversely, the detection rate of L858R was lower in the C method (13.8%) than in the S method (16.7%), but the difference was not significant (P = 0.252). De novo T790M was detected in one (0.2%) patient by the S method and in none by the C method. In re-biopsy after EGFR-TKI failure, the detection rates of T790M were as follows: 19 of 55 patients (34.5%) by the S method and 20 of 66 (30.3%) by the C method (P = 0.619). Conclusions: The different spectrums and sensitivities of EGFR mutations between the S and C methods were observed; however, they did not significantly affect clinical practice.
Practical implications of single-gene versus NGS testing in advanced NSCLC.
Authors: Yu Tiffany , Tradonsky Alison , Layton Andrew
Published: September 2018

e23106

Background: Genetic testing to guide 1st-line treatment is recommended for advanced non-small cell lung cancer (aNSCLC), but is complicated by small biopsy specimens available to test increasing numbers of biomarkers. This study compared commercially-available genetic tests for aNSCLC and the investigational use Oncomine™ Dx Target Test next generation sequencing (NGS) assay. Methods: This retrospective analysis used data from a large commercial lab, which offered clinical single-gene tests (EGFR therascreen, ALK Vysis, BRAF cobas, laboratory developed tests [LDT] for ROS1, BRAF, KRAS, MET, RET, and FGFR1); and NGS LDT (Illumina NextSeq 500). The lab also conducted investigational use of Oncomine Dx Target Test assay (Ion Torrent PGM Dx) on archival tissue. Clinical test orders received September 2015 – October 2016 were included. Sample rejection, test initiation, success rates, slide consumption, testing time, and turnaround time (TAT) were assessed. Results: Clinically, 3,857 single-gene and 219 NGS LDT tests were ordered on 1,479 samples for 1,436 patients. A total of 169 Oncomine Dx Target Tests were conducted. Conclusions: Investigational use of Oncomine Dx Target Test at this laboratory showed higher rates of test initiation and successful completion while using less tissue compared to either single-gene testing for ≥4 biomarkers or NGS LDT. This early experience suggests Oncomine Dx Target Test may enable therapy selection with multiple biomarker testing on small tissue samples for more aNSCLC patients compared to current methods. [Table: see text]
Comprehensive genomic profiling to merge precision medicine with immunotherapy.
Authors: Lyle Stephen , Tse Julie Y , Sun Ruobai , Huang Xiu , Russell Meaghan , Jiang Jane , Vuzman Dana , Protopopov Alexei , Eifert Cheryl
Published: September 2018

e23108

Background: Immunotherapy is rapidly emerging as one of the most promising therapeutic options in clinical oncology. However, not all patients will respond to immune-oncology drugs and diagnostic assays are urgently needed to identify biomarkers that predict response to these therapies. We developed an assay that utilizes next generation sequencing data to simultaneously determine different types of somatic changes in tumors. The assay was designed, in part, to facilitate identification of cancer patients most likely to respond to immunotherapies by detecting 1) CD274 (PD-L1) copy number alterations, 2) viral infections (HPV16/18 and EBV), 3) microsatellite instability (MSI), and 4) tumor mutation burden. Methods: We developed a 435-gene panel assay (CancerPlex) with the goal of identifying all the genomic changes that inform treatment decisions with the highest possible accuracy. We thoroughly evaluated the performance of the assay using reference samples that represent all classes of genetic variation, including SNPs, indels, copy number changes, rearrangements, HPV/EBV infection and MSI. FFPE clinical samples were also evaluated to assess the ability of the assay to detect genetic variation in complex, heterogeneous tumors. Results: The assay has excellent performance, with a mean sensitivity of 99.4% and specificity of 99.9% for detecting somatic mutations with an allele fraction as low as 10%. The assay identified the MSI status of colorectal tumors with the same sensitivity as immunohistochemistry but with greater sensitivity than PCR. We also showed that calculating tumor mutation burden using the 435-gene panel predicts response to pembrolizumab as effectively as using whole exome sequencing. Among 892 patients across all tumor types, 6.8% were identified as candidates for immunotherapy based upon high tumor mutation burden and/or MSI status. Conclusions: The capacity of the 435-gene panel to determine all of the critical genetic changes, tumor mutation burden, MSI status, CD274 (PD-L1) CNVs, and HPV/EBV status has important ramifications for patient treatment strategies, including identification of patients who are more likely to benefit from immune checkpoint inhibitor therapies.
Comparison of the c-MET gene amplification between primary tumor and metastatic lymph nodes in non-small cell lung cancer.
Authors: Fang Mei-yu , Xu Chun-wei , Wang Wen-xian , Wu Mei-juan , Zhuang Wu , Lin Gen , Chen Xiao-hui , Zhu You-cai , Liao Xing-hui , Du Kai-qi , Huang Yun-jian , Xu Hai-peng , Chen Yan-ping , Chen Gang , Lv Tangfeng , Song Yong
Published: September 2018

e23138

Background: Activation of c-MET lead to a wide range of biological activities. MET has recently been identified as a novel promising target in NSCLC, some c-MET inhibitors have been developed. The primary aim of this study was to evaluate the c-MET amplification status in advanced NSCLC and compare the consistency of c-MET amplification analyses in metastatic lymph nodes and tumor tissue.Methods: Real-time fluorescent quantitative polymerase chain reaction was used to test the tumor tissues in 368 patients of NSCLCs and 178 paired metastatic lymph nodes samples and compared the amplifications consistency inmetastatic lymph nodesand tissue samples, and analyzed the correlation between c-MET gene amplification and clinical characteristics of patients. Another 5 cases of normal lung tissue were taken as negative control.Results: The c-MET gene amplification rate was 8.97%(33/368) in tumor tissues . Of the178 paired cases, c-MET gene amplification was positive in 7.95%(15/178) cancerous tissuesand18.54%(33/178) in metastatic lymph nodes; Of these patients,13 were positive in the two kinds of samples. 20 cases in the paired group were detected positive c-MET in metastatic lymph nodes but was negative in cancerous tissues; 2 cases in the paired group were detected positive c-MET gene amplification in cancerous tissues but was negative in metastatic lymph nodes,there were statistically significant differences between the two samples (χ2= 45.536, P < 0.001). c-MET gene amplification was detected more in metastatic lymph nodes than the primary cancerous tissue. Consistency was evaluated by consistency test(Kappa = 0.482, P < 0.001).When lymph nodes were used as surrogate samples of primary cancerous tissues, sensitivity was86.67%, the specificity was 87.69%.Conclusions: More c-MET gene amplification positive were detected in metastatic lymph nodes compare with the primary cancerous tissue. c-MET gene amplification detected in lymph node metastases could screen more patients suitable for TKI therapy. Lymph node Metastasis can predict the c-MET gene amplification of primary tumor, and guide the clinical use of gene targeted drugs.
Activation of intracellular signaling pathways as a new type of biomarkers for selection of target anticancer drugs.
Authors: Buzdin Anton , Sorokin Maxim , Glusker Alexander , Garazha Andrew , Poddubskaya Elena , Shirokorad Valeriy , Naskhletashvili David , Kashintsev Kirill , Sokov Dmitry , Suntsova Maria , Roumiantsev Sergey , Kovalchuk Olga , Gaifullin Nurshat , Tkachev Victor , Borisov Nicolas
Published: September 2018

e23142

Background: Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in tumorigenesis. More than 150 different ATDs have been approved for clinical use worldwide, and the clinicians are faced with the problem of choosing the best therapeutic solution for each patient. The problem of efficient ATD selection remains largely unsolved and personalized approaches are needed to select the best ATD candidates for individual patients. Methods: We propose a new approach termed OncoFinder. It is based on digesting gene expression profiles for the analysis of activation of intracellular signalling pathways as a marker for the selection of target therapies. The original bioinformatic algorithms were integrated with the databases featuring molecular drug targets, compositions of signalling pathways, including the functional role of each gene product, for more than 1700 pathways (Buzdin, Front.Genet 2014; Ozerov, Nature Communications 2016). Results: We showed that pathway activation strengths are more stable and reliable biomarkers of cancer than the expressions of individual genes. OncoFinder allows to detect changes at the level of pathway activation and to predict the effectiveness of drugs based on the knowledge of their molecular targets. We applied it to find new biomarkers of clinical response to the ATD cetuximab; for modelling the combined chemotherapy of acute myeloid leukemia and combined anti-VEGF/BRAF therapy of melanoma. For two unrelated datasets obtained for colon cancer patients before treatment with the ATD bevacizumab, we were able to distinguish between those who responded to treatment and not (p < 0.01). We next assayed biopsies for kidney cancer patients with known responses to the ATD sorafenib. The responders and non-responders showed a significant difference (p = 0.02). Finally, the OncoFinder platform was prospectively used for decision making support to patients with advanced metastatic solid tumors (n = 23). The efficiency of the ATD treatment was 61% (complete + partial response, RECIST). Conclusions: OncoFinder method may be effective for predicting response to ATD based on high throughput gene expression profiles.
Regulation of the oxidative processes as a possible mechanism of iron nanoparticles antitumor action.
Authors: Kachesova Polina S. , Goroshinskaya Irina A. , Borodulin Vladimir B. , Nemashkalova Ludmila A. , Chudilova Anastasiya V. , Kit Oleg I.
Published: September 2018

e23160

Background: It has been shown that metal nanoparticles (NPs) can inhibit a tumor growth. Oxidative processes play important roles in tumor development and growth. The aim of this study was to determine parameters of oxidative stress in the blood of tumor-bearing animals depending on the antitumor effect of iron NPs (30-50 nm). Methods: Male rats with transplantable lymphosarcoma (LS) in the main group (n = 21) were treated with eight i.p. injections of iron NPs (total doses of 10 mg/kg bw), the control LS rats (n = 20) received saline i.p. The activity of catalase, superoxide dismutase (SOD), content of glutathione (GSH) and malondialdehyde (MDA) in the red blood cells (RBC) and ceruloplasmin oxidase activity (CP) and MDA content in blood plasma were measured. These parameters were analyzed in rats with complete tumor regression (n = 12) after NPs treated and in cases of tumor growth (n = 9). Results: In RBC of control group the level of GSH and catalase activity were increased compared to healthy rats by 24% and 14.3% (p < 0.05), respectively. In spite of activation of the given antioxidant system components, the MDA content in RBC was increased by 45% (p < 0.01) compared to normal values. In plasma of control group we observed an increase in MDA by 167.4% (p < 0.01) and a decrease in CP by 36.8% (p < 0.001). In the main group there was a decrease in blood MDA level and the antioxidant system reorganization. The degree of changes depended on the antitumor effect of NPs: rats with tumor growth showed a tendency to the decreasing MDA in RBC and normalization of plasma MDA; MDA in rats with LS regression was similar to normal values. In the main group the CP activity did not differ from the values in healthy rats. GSH increased in animals with tumor growth by 218.6% and in the animals with the effect - by 69% compared to normal values (p < 0.01). SOD activity in the rats with LS growth increased by 42% and in the rats with LS regression it decreased by 30% (p < 0.01). Conclusions: The data suggest the relationship between antitumor effect and modulating action on oxidative processes in LS rats treated by iron NPs. Iron NPs improved efficiency of antioxidant system in blood and contributed to suppression of oxidative stress associated with tumor growth.