tbuckley/cabot-search huggingface dataset:
Prospective study of biomarkers in squamous cell carcinoma of the anal canal (SCCAC) and their influence on treatment outcomes: Five-year long-term results.
Authors: Camila Motta Venchiarutti Moniz, Rachel Pimenta Riechelmann, Maria Ignez Braghiroli, Suilane Coelho Ribeiro, Thomás Giollo Rivelli, Giovanni M. Bariani, Andre Tsin Chih Chen, Caio Nahas, Renata Colombo Bonadio, Cinthia Ortega, Rejane Franco, Sibele Meireles, Allan Andresson Lima Pereira, Jorge Sabbaga, Renata A. Coudry, Paulo Marcelo Hoff
Journal: Journal of Clinical Oncology (2020)

4053 Background: Chemoradiation (CRT) is a curative treatment for SCCAC. However, some patients (pts) present primary CRT resistance. As a rare tumor, there is a lack of prospective studies of prognostic factors in this setting. Methods: This prospective cohort study was aimed to evaluate predictive biomarkers (Ki-67, PD-L1, Human papillomavirus (HPV), HIV status, and tumor DNA mutations) in SCCAC. We published the 6 months (m) response rate (RR) of this cohort showing that HIV- were 5.7 times more likely to achieve response 6m post CRT (OR 5.72, CI 95% 2.5-13.0, P &lt; 0.001). Now we report the long-term follow-up results of 5-year progression-free survival (PFS) and overall survival (OS). Eligible pts had T2-4/N0-3/M0 disease and were candidates to standard CRT. DNA mutations were analyzed by next-generation sequencing (NGS). HPV positivity was tested by PapilloCheck Test. KI-67 and PD-L1 were evaluated by immunohistochemistry. Results: 78 pts were recruited from Jan/2011 to Dec/2015. 75 were evaluable for PFS and OS. The median age was 57 years; 49 (65%) were stage III, and 9 (12%) were HIV+. HPV was evaluated in 67 and found in 47 (70.1%); HPV16 was the most common. PD-L1 was tested in 61; 10 (16.4%) had positive expression &gt; 1%. Ki-67 was performed in 65, with a median of 50% (range 1-90%). The median follow up is 66m. 5-year PFS and OS rates were 63.3% (95% CI 51.2-73.2%) and 76.4% (95% CI 64.8-84.6%), respectively. In a multivariate analysis, age (HR 1.06, P = 0.022, IC 95% 1.01-1.11) and absence of complete response at 6m (HR 3.36, P = 0.007, IC 95% 1.39-8.09) was associated with inferior OS. The OS rate was 62.5% in HIV+ group (95% CI 22.9-86%) in comparison with 78% (95% CI 65.7-86.3%) among HIV- pts, although this difference was not statistically significant (P = 0.400). A tendency to inferior OS was observed among pts with p53 codon 72 polymorphism (HR 2.83, P = 0.181, 95% CI 0.61-13.02). Other tumor mutations, HPV, Ki-67 expression, and PD-L1 expression, were not associated with PFS and OS. Conclusions: HIV- pts were 5.7 times more likely to achieve response 6m post CRT. The absence of complete response at 6m was the main factor associated with poor 5-year OS. New strategies of follow up and complementary treatment should be studied in late responders and HIV+ pts to ensure the success of curative treatment. Clinical trial information: 36211 .
Barriers to the integration of tobacco cessation programs in primary care practices in Tennessee.
Authors: Nicholas C. Richardson, Bruce Behringer, Michael D. Warren
Journal: Journal of Clinical Oncology (2016)

e18187 Background: Tobacco use increases the risk of lung and many other tobacco related cancers, with higher risk conferred by longer duration and more intensive tobacco use. Further, tobacco use is associated with other adverse health outcomes, such as cardiovascular disease, stroke and chronic obstructive pulmonary disease. More than 42.1 million adults currently smoke in the U.S. and the rate of cigarette smoking remains higher than the national average in Tennessee. Starting in 2013 and using Tobacco Master Settlement funding, the Tennessee Department of Health initiated a goal to further integrate tobacco cessation interventions into community primary care clinics. However, several barriers arose to successful promotion and integration of community tobacco cessation. The objective of this study was to identify common barriers to integrating successful community practice-based tobacco cessation interventions and develop an action plan to facilitate successful program establishment. Methods: Semi-structured, key informant interviews were conducted with seven Tennessee county department of health directors to assess facilitators and barriers to implementation of evidence-based tobacco cessation interventions within community primary care practices. Facilitators or barriers were organized into themes that included intra-personal factors, institutional factors and community factors as defined by the socio-ecologic model. Results: The barriers elucidated included time constraints, documentation challenges, organizational culture, resource availability and allocation, leadership approval and lack of partnerships. The barriers identified highlight the need for an organized action plan to facilitate integration of a tobacco cessation intervention. The action plan developed includes: 1) an effective program champion; 2) utilization of local data; 3) adequate staff resources; 4) community education; and 5) strategic planning with key stakeholders. Conclusions: Leveraging strategies to offset common barriers to the integration of tobacco cessation interventions are essential to establish practical, evidence-based tobacco cessation and prevention programs into clinical practices.
Activity of the immunologic doublet of lenalidomide plus obinutuzumab in relapsed follicular lymphoma: Results of a phase I/II study.
Authors: Nathan Hale Fowler, Sattva Swarup Neelapu, Felipe Samaniego, Sheryl Forbes, Fredrick B. Hagemeister, Luis Fayad, Lei Feng, Francesco Turturro, Jason R. Westin, Janine Arafat, Eleanor Neal, Loretta J. Nastoupil
Journal: Journal of Clinical Oncology (2017)

7531 Background: Relapsed follicular lymphoma (FL) remains a challenge and salvage regimens are associated with toxicity and limited control. Outcomes are linked to the immune microenvironment and lenalidomide and rituximab are highly active in FL. Obinutuzumab has increased ADCC compared to rituximab in preclinical models and is approved for relapsed FL. We hypothesized that the immunologic properties of obinutuzumab and lenalidomide would be synergistic. The study objective was to determine the MTD of lenalidomide with obinutuzumab in relapsed FL and describe the efficacy of the combination. Methods: This open label phase I/II study enrolled Gr 1-3a FL. Transformation was excluded. Lenalidomide was given on D 2-22 with 1000mg obinutuzumab on D1, 8, 15, and 22 of cycle 1 and on D1 for up to 12 cycles (28 days/cycle). Obinutuzumab was given every 2 months thereafter for up to 30 months in pts who responded following doublet therapy. During dose escalation, 3 cohorts were planned with 10, 15 and 20mg of lenalidomide. Phase II planned to enroll 30 pts at MTD with efficacy and safety as primary endpoints. Results: All 36 pts with FL enrolled (6 in dose escalation and 30 at MTD), and are eligible for efficacy and safety analysis. The median age was 65 with a median of 2 prior therapies. No DLTs were observed in phase I, and 20 mg of lenalidomide was used for phase II. To date, the most common all grade non-heme toxicities were fatigue(83%), diarrhea(67%) and rash(53%). Grade 3+ toxicities included neutropenia (23%), infection (11%) and fatigue (8%). The overall response rate was 100% with 78% (95%CI 60.85-89.88%) of pts attaining complete response (CR/Cru). All pts with rituximab refractory FL (13) responded. At a median follow up of 14 months, 10 pts progressed. The estimated 24 month PFS is 61% (95% CI 43-87%). Conclusions: Lenalidomide and obinutuzumab is highly active with durable remissions in relapsed FL, with all pts responding and 78% achieving CR. The majority of pts remain on therapy and the combination appeared safe. Correlatives are ongoing to identify biomarkers of response and frontline studies of the combination are currently enrolling. Clinical trial information: NCT01995669.
Utilization of an electronic medical record trigger to promote palliative care consultation in ambulatory oncology.
Authors: Sherri L. Rauenzahn, Susanne Schmidt, Nazneen Ali, Laura LaNiel Tenner
Journal: Journal of Clinical Oncology (2017)

e18201 Background: Research insupportive care demonstrates improvements in overall survival, quality of life, symptom management, and reductions in the cost of care. Despite the American Society of Clinical Oncology recommendation for early concurrent supportive care in patients with advanced cancer and high symptom burden, integrating supportive services is challenging. Our aims were to 1) implement an electronic medical record (EMR) provider alert of high symptom burden based on Edmonton Symptom Assessment Scale (ESAS) criteria and 2) determine the impact an alert has on supportive service referrals. Methods: ESAS scores were implemented in medical ambulatory oncology clinics to quantitatively assess symptom burden. An EMR alert was programmed for a total ESAS score &gt; 30 and any single response of ≥9 to capture approximately 15% of our high symptom burden patient population. The provider could elect to accept the alert placing an order for palliative consultation or decline the prompt. Referral rates and symptom assessment scores were followed as metrics for EMR alert efficiency. Results: Over 10 months, 9,710 patient visits used the ESAS system resulting in 7,707 fully completed ESAS scores (79.4% completion rate). There were 78 total consults to palliative care, a referral rate of less than 1% of the population, which was unchanged from prior to trigger implementation. Of the total completed ESAS forms, the trigger alerted 686 times (8.9% of patient visits) with only 55 of those triggers leading to a supportive care referral (8.0%). Conclusions: This project highlights the challenges of an EMR based alert system and the need for continued efforts to improve supportive care referrals through provider education and tool implementation. [Table: see text]
Biomarker results and preclinical rationale for combination lenvatinib and pembrolizumab in advanced endometrial carcinoma.
Authors: Vicky Makker, Allen Lee Cohn, Matthew H. Taylor, Yukinori Minoshima, Yu Kato, Ryo Dairiki, Michio Kanekiyo, Ayako Yachie, Kotaro Kodama, Pallavi Sachdev, Junji Matsui, Yasuhiro Funahashi, Drew W. Rasco
Journal: Journal of Clinical Oncology (2018)

5597 Background: Lenvatinib (LEN) is a multikinase inhibitor of VEGFR 1−3, FGFR 1−4, and other targets; pembrolizumab (PEM) is an anti–PD-1 antibody. We report biomarker analyses from a phase 1b/2 trial in advanced endometrial cancer (EC) and preclinical rationale for the activity of combination LEN + PEM. Methods: In an exploratory analysis, 41 candidate serum biomarkers for LEN and PEM were assessed using immunoassay panels in 38 patients with EC receiving LEN + PEM at baseline, cycle 1 day 15 (C1D15), and C2D1. Data cutoff: May 31, 2017. Tumor-associated macrophages (TAM) were assessed in mouse syngeneic tumor models by flow cytometry and immunohistochemistry. RNAseq transcriptomes of tumors from mice treated with LEN, anti–PD-1, or LEN + anti–PD-1 were subjected to weighted gene coexpression network analysis for pathway enrichment analyses. Results: At C1D15 and C2D1 of LEN + PEM, significant changes were seen in the levels of 16 and 18 of 41 biomarkers, respectively, including increased levels of interferon (IFN)-γ and IFN-γ–regulated chemokines (CXCL9, CXCL10, CXCL11; all P < 0.05). Of these, significant associations were found between increases in CXCL9 and CXCL10 levels and patients with compete, partial, or unconfirmed partial responses (all P < 0.05). Preclinical model experiments in vivo showed that LEN alone significantly depleted the TAM population in excised tumors (P < 0.01). Transcriptome analyses of tumors from mice treated with LEN + anti–PD-1 showed that genes specifically regulated by the combination were significantly enriched for genes involved in signaling pathways associated with immune modulation, including IFN signaling (FDR P as low as 1.50 x 10-9). Conclusions: In patients with advanced EC, LEN + PEM was associated with changes in several biomarkers, including IFN-γ–regulated chemokines, some of which may be associated with clinical response. In vivo preclinical experiments suggest that LEN monotherapy may modulate tumor microenvironment by decreasing the local TAM population, whereas LEN + anti–PD-1 may act via a mechanism that includes the IFN signaling pathway. Overall, these findings provide preclinical rationale for the activity of combination LEN + PEM. Clinical trial information: NCT02501096.
Updated results of REGOMA: A randomized, multicenter, controlled open-label phase II clinical trial evaluating regorafenib in relapsed glioblastoma (GBM) patients (PTS).
Authors: Giuseppe Lombardi, Gian Luca De Salvo, Roberta Ruda, Enrico Franceschi, Marica Eoli, Marina Faedi, Andrea Pace, Ivan Lolli, Simona Rizzato, Domenico Germano, Francesco Pasqualetti, Miriam Farina, Giovanna Magni, Luisa Bellu, Ardi Pambuku, Eleonora Bergo, Stefano Indraccolo, Marina Paola Gardiman, Riccardo Soffietti, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2018)

2047 Background: There is no established treatment regimen for recurrent GBM. GBMs have activation of multiple signaling pathways in the tumor microenvironment, including the receptor tyrosine kinases, VEGFR, FGFR, and PDGFR. REG, an oral multikinase inhibitor, inhibits these angiogenic kinases and the mutant oncogenic kinases KIT, RET, and B‐RAF. Methods: We present, after the first analysis, the updated results of REGOMA trial. The primary aim of this trial was to assess REG activity in prolonging overall survival (OS) in PTS with relapsed GBM after surgery and Stupp regimen (α = 0.2, 1-sided; β = 0.2). Secondary objectives were PFS, disease control rate (DCR), safety, quality of life (QoL); exploratory objectives included analysis of metabolic tissue biomarkers as possible predictors of response. PTS with histologically confirmed GBM, ECOG PS 0‐1, documented disease progression were randomized 1:1 to receive REG 160 mg/day (3 weeks on, 1 week off) or lomustine (LOM) 110 mg/m2 (every 6 weeks) until disease progression or unacceptable toxicity. Tumor response was evaluated by brain MRI every 8 weeks according to the RANO criteria. Results: 119 PTS were randomized (n = 59 REG; n = 60 LOM) and stratified for surgery at recurrence; baseline characteristics, including MGMT methylation status, were balanced. Median age was 57.3 yrs; 27 PTS (22.7%) had surgery at recurrence, 22% and 23.3% in REG and LOM arm. At the time of analysis (cut-off date: Dec 31, 2017), median follow up was 15.4 months(m), 99 PTS had died. Median OS was 7.4m (95% CI 5.8-12.0) for REG and 5.6m (95% CI 4.7-7.3) for LOM (HR = 0.50, 80%CI 0.38-0.65; p = 0.0007; 1-sided Log-rank test); 12m-OS rates were 38.9% and 15.0% for REG and LOM. 6m-PFS rates were 16.9% and 8.3% (HR = 0.65; 95% CI 0.45‐0.95; p = 0.0223) for REG and LOM , DCR was 44.8% and 21.1% (p = 0.009) for REG and LOM. Grade ≥3 adverse events were reported in 56% and 40% for REG and LOM, no treatment-related deaths were reported. Conclusions: In this multicenter, randomized study, REG significantly improved OS, PFS and DCR in recurrent GBM PTS. REG treatment was feasible and well tolerated. QoL and biomarker analyses are ongoing. A phase 3 study will be planned. Clinical trial information: NCT02926222.
CQC: Trusts must do more to protect mental health patients from sexual abuse
Authors: Jacqui Wise
Journal: BMJ (2018)

New national guidance is needed to improve the sexual safety of patients in mental health wards, the health and social care regulator for England has said, after finding that distressing sexual incidents were common.

The Care Quality Commission also wants to see a stronger reporting system and more training for staff.1

In its report the CQC said that people admitted to mental health wards included those who were vulnerable to sexual abuse and those who lacked the mental capacity to make informed decisions about sexual relationships. This, combined with overcrowded wards, old and unsuitable buildings, staff shortages, and a lack of basic training, increased the risk of harm to patients and to staff.

The report said that people who …
Economic evaluation of the combination of talimogene laherparepvec (T-vec) plus ipilimumab (T-vec+Ipi) versus ipilimumab (Ipi) in patients (pts) with advanced unresectable melanoma.
Authors: Abdulaali Almutairi, Nimer Alsaid, Mok Oh, Hani M. Babiker, Ali McBride, Ivo Abraham
Journal: Journal of Clinical Oncology (2018)

e21545 Background: A recent trial comparing T-vec+Ipi vs Ipi found no differential benefit in progression-free survival (PFS) (HR 0.83, 95%CI 0.56–1.23), but noted objective response rates (ORR) of 39% vs 19% resp. in pts with advanced melanoma. We aimed to assess the cost-effectiveness of T-vec+Ipi vs Ipi from the US payer perspective. Methods: A two-state Markov model (progression-free; progression/death) was specified. Kaplan-Meier curves for PFS were digitized, data extracted, Weibull distributions fitted, and data extrapolated to a life time horizon. Medication costs (wholesale acquisition cost) were per Redbook and pt monitoring and adverse event (AE) management costs per CMS reimbursement schedules and literature. Utility values for PFS and complete/partial response were obtained from literature. Disutility value for AEs was assumed to be similar in both arms. Discount of 3% was applied when survival exceeded 1 year. Following extrapolation to the time horizon, absolute (LY) and quality adjusted life year (QALY) and ORR for each treatment was determined. Incremental cost effectiveness (ICER) and cost utility (ICUR) ratios were estimated, as well as the incremental cost per 1% increase in ORR. Base case analyses (BCA) were validated by probabilistic (PSA) and one-way sensitivity analyses (OWSA). Results: In BCAs, LY and QALY gained by T-vec+Ipi were 0.17 and 0.16 resp. at incremental cost of $358,382, yielding ICER of $2,235,273/LY and ICUR of $2,408,002/QALY gained. The estimated incremental cost per 1% increase in ORR was $1,731,558. PSAs confirmed BCA results with estimated ICER of $1,630,517/LY and ICUR of $1,816,960/QALY gained. In OWSAs, PFS HR and utility for response were the most influential parameters on cost-effectiveness outputs. Conclusions: With T-vec+Ipi combination therapy not showing a PFS and only an ORR benefit, this regimen is expensive compared to Ipi monotherapy and requires significant WTP thresholds to be considered cost-effective to US payers.
Oncological outcomes of function preserving gastrectomy for early gastric cancer: A multicenter case-controlled analysis comparing pylorus-preserving gastrectomy versus conventional distal gastrectomy.
Authors: Masaki Aizawa, Michitaka Honda, Naoki Hiki, Takahiro Kinoshita, Hiroshi Yabusaki, Souya Nunobe, Hidehito Shibasaki, Atsushi Matsuki, Takayuki Abe, Masahiro Watanabe, Atsushi Nashimoto
Journal: Journal of Clinical Oncology (2016)

4034 Background: The aim of this study was to clarify the oncological safety of pylorus-preserving gastrectomy (PPG) compared with conventional distal gastrectomy (DG). Methods: From three institutions specializing in cancer, the medical records for a cohort of 2,898 consecutive patients who had undergone DG (n = 2,208) or PPG (n = 690) for clinical Stage I gastric cancer between January 2006 and December 2012 were analyzed. A propensity score for each patient was estimated based on 38 preoperative clinical and tumor related factors. After propensity score matching, 1,004 patients (DG = 502, PG = 502) were included in the analysis. The overall survival, relapse free survival and occurrence of secondary gastric cancer were then compared. The median (range) observation period was 48.6 (1-109.8) months. Results: The patients who received a PPG were relatively young age (58.7 ± 10.4 years) and had a high performance status, middle gastric tumor, solitary tumor, clinical T1, and clinical N0. The 5-year overall survival was 98.4 % for the PPG group and 96.6% for the DG group (Hazard ratio: 0.48, 95%CI: 0.21 - 1.09, P= 0.07). The 3-year relapse-free survival was 99.5% for the PPG group and 98.0% for the DG group (HR: 0.39, 95%CI: 0.12 – 1.33, P= 0.12). Postoperative secondary gastric cancer was encountered in 8 (1.6 %) in the PPG group and 4 patients (0.8 %) in the DG group. No significant differences in either overall survival, relapse free survival or the occurrence of secondary gastric cancer were observed between the two groups. Conclusions: Given the adequate estimation of the clinical tumor stage, the oncological safety of PPG for clinical T1N0 gastric cancer in the middle stomach was comparable to that of DG.
Study of clinical characteristics of breast cancer among women older than 70 years in a single institute.
Authors: Purva Sharma, Elie Donath, Beth Byron, Shachar Peles
Journal: Journal of Clinical Oncology (2018)

e12578 Background: Breast cancer is the most common type of cancer in women. 35% of breast cancer is reported in women older than 70 years. This study was performed with aim to evaluate the clinical characteristics of breast cancer among women above 70 years. Methods: In this retrospective study, all breast cancer patients diagnosed between 2009 and 2016 at JFK Medical Center were included. All the necessary data about age, race, tumor histopathology, clinical staging, hormone receptor status, type of surgery and type of adjuvant therapy (radiotherapy, chemotherapy, hormone therapy) were extracted from these files. Data was analyzed with SPSS software (version 16). P < 0.05 was considered significant. Results: Out of the 1250 patients, 563(45%) patients were greater than 70 years of age out of which 95% belonged to the Caucasian race. The most common site in this age group was the upper outer quadrant seen in 224 (39.7%) patients. 275 patients presented with Stage 1A (48.8%) which was almost half the number of patients. Those presenting with stage 2A and stage 3A were 112 (20%) and 21 (3.7%) respectively. Most common histology was infiltrating duct carcinoma, seen in 338(60%) patients. The second most common types were the infiltrating duct mixed with other types of carcinoma and intra-ductal carcinoma, non-infiltrating. In terms of hormone receptor status, ER positivity was seen in 492 (87.3%). Similarly, PR positivity was seen in 424 (75.3%). Chemotherapy was used in only 44 patients (8%). Radiation therapy was used in 288 (51%) and 196 (35%) patients were treated with hormonal therapy. Only 8 patients were treated with immunotherapy. Conclusions: The most common type of breast cancer in women above 70 years is infiltrating ductal carcinoma and the most common stage of disease is IA. Most patients are estrogen and progesterone receptor positive. Therefore, it is recommended to pay more attention to their specific clinical characteristics in choosing the treatment approach for this patient population.