tbuckley/cabot-search huggingface dataset:
Checkpoint inhibitor treatment in patients with isolated in-transit melanoma metastases.
Authors: Lucy Storey, Mohammed Abdul-Latif, Sophia Kreft, Emma Barrett, Lisa M Pickering, Maartje W. Rohaan, Sobia Ahmed, Thomas K. Eigentler, Jessica Cecile Hassel, Sebastian Haferkamp, Frank Meiss, Theresa Steeb, Heather May Shaw, Christian U. Blank, Alexander Christopher Jonathan Van Akkooi, James M. G. Larkin, Bastian Schilling, Paul Lorigan, Paul D. Nathan
Journal: Journal of Clinical Oncology (2020)

10070 Background: In the context of multiple in-transit melanoma metastases without nodal involvement, a variety of treatment modalities have historically been employed including surgery, laser, isolated limb perfusion/infusion, intralesional interleukin-2, T-VEC and electrochemotherapy. Unfortunately, most patients treated with these modalities experience subsequent disease progression. While checkpoint inhibitors (CPI) are a standard of care for bulky unresectable stage III and for stage IV melanoma, patients with isolated in-transit metastases were rarely included in registration studies. There are anecdotal reports of lower response rates in these patients despite them having disease characteristics that would usually be associated with a good response. Methods: We report data from 11 retrospective patient cohorts treated at cancer centres across Europe who received CPI between 2016 and April 2019. All patients had multiple in-transit metastases without clinical or radiological evidence of nodal or distant disease. Disease response was assessed using CT, PET-CT or MRI depending on clinical indication. All patients had at least one prior resection of loco-regional relapsed disease and were deemed not curable by further surgery. Results: Sixty three patients meeting criteria were identified, 40 females and 23 males. Median age was 72 years and 54 (86%) patients had a normal lactate dehydrogenase (LDH). 19 (30%) patients had a BRAF mutation. At treatment initiation, the majority 55 (87.3%) received single agent PD-1 inhibitor, 7 (11.1%) combination ipilimumab + nivolumab and 1 (1.6%) received single agent anti-CTLA 4. The overall response rate was 62% for the full population. The response rate with anti-PD1 monotherapy was 59%. With a median FU of 23 months, the median PFS was 26 months, median OS not reached. OS estimates with 95% CI: 12 month - 93% (87-100%), 24 month - 88% (80-98%), 36 month - 80% (67-95%). Conclusions: The results show a high response rate to CPI in patients with in-transit metastases and support early treatment with CPI following identification of in-transit metastases not curable with surgery whilst disease characteristics remain favourable.
Depressive factors associated with breast cancer.
Authors: Alexandre Alberto Mendes Tostes, Carla Simone Moreira de Freitas, Aleida Nazareth Soares
Journal: Journal of Clinical Oncology (2020)

e13091 Background: In Brazil, the estimated cancer for the 2019 was approximately 420 thousand new cases. In Minas Gerais, the estimate was 5,360 new cases. Objective is to relate comorbid humor disorders with breast cancer in patients treated at a cancer hospital. Methods: Cross-sectional and descriptive study with a sample of 100 patients with Breast Cancer (BC), chosen at random. Data were collected at a Muriaé cancer hospital in, from January to June 2019. Semi-structured sociodemographic and clinical suervey and the Beck Depression Inventory (BDI-II) to check for signs and symptoms of depression. Data analysis was performed using the statistical packages SPSS. To check if there was a difference between groups in continuous variables, Shapiro-Wilk test; the data considered normal the Student's t test (parametric test) and the data considered non-normal the Mann Whitney test (non-parametric test). For categorical variables, the chi-square test, Fisher's exact test or Monte Carlo simulation. As for the interpretation of Beck's inventory, the scores were analyzed and demonstrated according to the standardized by the inventory, that is, the result obtained was the sum of the individual items, reaching a maximum score of 63 points. The classification of the levels of depression varies between minimum, mild, moderate and severe, thus indicating the intensity of the depression. The study was developed according to Resol. 466/12, of the National Health Council. Results: Average age of women with BC in both groups was 55 years, with low education (43%), married (48%), and, 50% of them have one or more children and, 70% do not work. Regarding the use of drugs and/or medication and smoking, it was higher in group B (with depression) (64.6%). In the other variables (family relationship, self-preservation of health, affected daily life, family/social isolation, living with other women with BC, perspective of life after treatment, type of follow-up), the proportion was always higher in group B compared to group A (without depression). The time of diagnosis, staging, type of surgery and edema in the upper limb did not show significant difference between the two groups analyzed. Regarding the type of treatment, there was a significant difference, mainly showing that proportionally the Surgery + Chemotherapy treatment is higher in the group without depression while the and Surgery + Chemotherapy + Radiotherapy + Hormone therapy are proportionally higher in the group with depression. Conclusions: Women with BC have depressive symptoms frequently and should be investigated and treated so that the negative impacts can be minimized.
Melanoma recurrence after adjuvant targeted therapy: A multicenter analysis.
Authors: Prachi Bhave, Lalit Pallan, Victoria Atkinson, Justine Vanessa Cohen, Vanna Chiarion-Sileni, Marta Nyakas, Katharina C. Kaehler, Elizabeth Plummer, Paolo Antonio Ascierto, Lisa Zimmer, Celeste Lebbe, Andrea Maurichi, Caroline Robert, Thierry Lesimple, Sapna Pradyuman Patel, Judith M. Versluis, Muhammad Adnan Khattak, Andre Van Der Westhuizen, Matteo S. Carlino, Andrew Mark Haydon
Journal: Journal of Clinical Oncology (2020)

10016 Background: Adjuvant targeted therapy (TT) improves relapse free survival (RFS) in patients (pts) with BRAF mutant stage 3 melanoma. The outcomes and optimal management of pts who relapse after adjuvant TT is unknown. Methods: Pts from 21 centres with recurrent melanoma after adjuvant TT were included. Disease characteristics, adjuvant therapy, recurrence, treatment at relapse and outcomes were examined. Results: 87 pts developed recurrent melanoma; 21 (24%) during and 66 (76%) after cessation of adjuvant TT. Median time to 1st recurrence was 16.3 months with median follow up after 1st recurrence of 31 months. 30 (34%) pts recurred locoregionally, 51 (59%) pts developed distant recurrence and 6 (7%) pts had both. Of those who recurred locoregionally, 23/30 (77%) pts underwent surgery to no evidence of disease, only 3 (13%) of which received adjuvant anti-PD1 therapy, and 15/30 (50%) subsequently developed distant disease. 29 (33.3%) pts have died. 75 (86%) pts received systemic therapy at either 1st or subsequent recurrence. 40 (46%) pts received 1st line anti-PD1 based therapy (single agent anti-PD1, anti-PD1 with ipilimumab or anti-PD1 with investigational agent), 12 (14%) pts received ipilimumab monotherapy, 18 (21%) pts received retreatment with combination BRAF/MEK inhibitors and 5 (6%) pts received other agents (chemotherapy, TVEC). 57 (66%) pts had disease that was assessable for response rate (RR). RR after relapse was 69.7% (23/33) to 1st line anti-PD-1 based therapy, 46% (6/13) to TT and 9% (1/11) to ipilimumab monotherapy (Table). Median overall survival (OS) from date of 1st recurrence for all pts was not reached. OS varied by drug class received as 1st line systemic therapy after relapse. 3 year OS was 79% for anti-PD-1 based therapy, 55% for TT and 25% for ipilimumab. Conclusions: This study demonstrates that pts who relapse after adjuvant TT may respond to subsequent immunotherapy at similar rates to the treatment naïve setting. [Table: see text]
Quality of life in elderly patients with cancer
Authors: 任光圆
Journal: BMJ (2005)

当今临床医学的特点之一是更加重视患者的生活质量,即不但要求把病治好,而且要提高生活质量.老年肿瘤患者由于自身条件的特殊性,往往很难选择合适的治疗方案,然而若不给予积极处理,这些患者可能危险性更大.因此,应有合适的评价方法以便更好地评价老年肿瘤患者治疗方案的利弊.生活质量(quality of life, QOL)是一套评价健康水平的指标体系,测定躯体功能、心理功能、社会功能、症状及治疗毒性不良反应等.QOL可作为临床肿瘤研究的终点指标,尤其适用于当治疗并不显著改善患者生存率,或者由于药物不良反应而不能决定是否选择积极的药物治疗时,如老年肿瘤患者治疗方案的选择.当然,在肿瘤治疗的选择中,应优先考虑是否适合积极的抗肿瘤治疗,而不是首先考虑生存率[1].但老年患者文盲率高,对QOL问卷调查的依从性差,这给数据采集与分析带来了困难.目前的肿瘤临床试验还较少把老年患者纳入研究范围,尤其是75岁以上患者,但随着老年肿瘤患者的不断增多,QOL的评价已变得非常重要。
Characteristics of elderly frequent clinic attenders in a Shanghai community health service center
Authors: Nana Li, Juan Shou, Yaling Li, Xiaoyang Han
Journal: BMJ (2019)

Objective
To analyze the characteristics of elderly frequent clinic attenders in a Shanghai community health service center.


Methods
The medical records of patients over 60 year who visited Shanghai Weifang Community Health Center clinic from October 2014 to October 2017 were obtained from the hospital outpatient management system. The persistent frequent attenders were defined as whose visiting times were among the top 10% of attendance in the three consecutive years. The general condition and disease characteristics of persistent frequent attenders were analyzed and compared with those of non-frequent attenders and transient frequent attenders.


Results
There were total 19 240 patients paying 1 171 thousand clinic visits in the center for three years, the persistent frequent attenders accounted for 5.3% (1 029) of total patients and had 21.4% of total visits (251 thousand); those figures for transient frequent attenders were 10.2%(1 965) and 23.9% (280 thousand); for non-frequent attenders were 84.5% (16 246) and 54.7% (640 thousand), respectively. The average annual visits of three groups were (81.4±27.5), (47.5±21.4) and (13.1±11.1) times, respectively. The reasons for encounter in persistent frequent attenders were: coronary heart disease (11.2%, 48 thousand), cerebral insufficiency (3.5%, 15 thousand), joint pain (2.5%, 11 thousand), osteoporosis (2.9%,13 thousand) and sequelae of stroke (2.1%, 9 thousand). Age above 70(OR=2.163, 95%CI: 1.872-2.498), age above 80 (OR=2.243, 95%CI 1.895-2.655), female sex (OR=1.426, 95%CI: 1.249-1.627) and contracting general practitioners (OR=5.665, 95%CI 4.217-7.611) were associated with persistent frequent attendance (P<0.05).


Conclusion
Elderly frequent attenders occupy large outpatient resources of community health center, and age, gender and contracting status could affect their attending frequency.


Key words: 
Community health services; Outpatients; Aged
Value of multigene panel retesting of families with <i>BRCA1/2</i> mutation-negative hereditary breast and ovarian cancer (HBOC).
Authors: Ekaterina Meshoulam Nikolaeva, Raul Terés, Daniela Camacho, Aida Bujosa, Maria Borrell, Pablo Gallardo, Berta Martin, Nuria Calvo, Consol Lopez, Rosa Alfonso, Carla Sola, Monia Cornet, Nuria Cliville, Adriana Lasa, Ariadna Tibau, Cristina Arqueros, Agusti Barnadas, Teresa Ramon y Cajal
Journal: Journal of Clinical Oncology (2020)

1582 Background: Despite the use of clinical eligibility criteria and mutation predictive models, a great proportion of families are negative for germline mutations in BRCA1/2 genes. Traditionally, risk assessment of inconclusive results included the recommendation of high-risk surveillance protocol, the update of incident cancer cases in the family and the consideration of additional testing to rule out the possibility of phenocopy. More recently, next generation sequencing multigene panels have become a standard practice in cancer genetics clinics worldwide. We addressed the value of multigene panel retesting of BRCA1/2 negative HBOC families in our institution. Methods: After genetic counseling session and informed consent, a total of 137 individuals (119 probands and 18 extra cancer-affected relatives) from distinct BRCA1/2 negative families were retested using a panel containing 11 breast and ovarian cancer susceptibility genes ( BRCA1/2, PALB2, ATM, CHEK2, PTEN, TP53, STK11, BRIP1, RAD51C, RAD51D). Results: According to the BOADICEA model, the remaining probability of mutation in BRCA1/2 or PALB2 genes in our cohort was 5.5% (0.1-61). The reasons for considering retesting were the addition of any incident cancer diagnosis in 33 cases (24%), a prior study with a low sensitivity screening technique (dHPLC) in 6 families (5%) and the expansion of the study to other putative breast and ovarian susceptibility genes in 98 families (71%). Overall, 3 pathogenic (2 BRCA2, 1 CHEK2) and 8 likely pathogenic variants (1 BRCA2, 4 CHEK2 and 3 ATM) were found. The prevalence was 8%. The detection rate among 19 families with a &gt; 10% remaining probability of mutation in BRCA1/2 and PALB2 genes was 26%. The 3 clinically significant variants in BRCA2 were detected in 2 families and 1 updated cancer family history (BOADICEA remaining probability of 59, 61 and 12%, respectively). Cascade testing was subsequently done in 15 relatives resulting 8 in mutation carriers and 9 true negatives. Conclusions: Our results support the value of updating cancer incident cases and considering expanded panels in selected families.
HORIZON (OP-106): An exploratory analysis of time-to-next treatment (TTNT) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) who received melflufen plus dexamethasone (dex).
Authors: Maria-Victoria Mateos, Albert Oriol, Alessandra Larocca, Joan Blade, Michele Cavo, Paula Rodríguez Otero, Xavier Leleu, John W. Hiemenz, Hani Hassoun, Cyrille Touzeau, Adrian Alegre, Agne Paner, Christopher Maisel, Amitabha Mazumder, Anastasios Raptis, Johan Harmenberg, Stojan Zavisic, Sara Thuresson, Oskar Öhman, Paul G. Richardson
Journal: Journal of Clinical Oncology (2020)

e20570 Background: Melflufen is a novel peptide-drug conjugate that rapidly delivers a cytotoxic payload into tumor cells. Melflufen + dex showed efficacy and a manageable safety profile in pts with poor-risk, heavily pretreated RRMM in the phase 2 HORIZON study (Mateos et al. ASH 2019. Abs. 1883). For pts with RRMM, longer TTNT is indicative of disease stabilization and clinical benefit and is associated with lower costs (Chen et al. J Manag Care Spec Pharm. 2017). This report of TTNT after melflufen + dex from HORIZON is, to our knowledge, the first report from a trial population with such advanced RRMM. Methods: Pts with RRMM who had received ≥2 prior lines of therapy, including an IMiD and a proteasome inhibitor (PI), and were refractory to pomalidomide and/or an anti-CD38 monoclonal antibody (mAb), received melflufen 40 mg (IV on d1 of each 28-d cycle) + dex 40 mg/wk until disease progression or unacceptable toxicity. The primary endpoint was overall response rate. Secondary endpoints included progression-free survival (PFS) and safety. TTNT was defined as the time from start of melflufen + dex to first subsequent therapy. Results: Overall, 154 pts were treated (data cutoff, Oct 1, 2019); median age was 64.5 y (range, 35-86), 32% had International Staging System stage 3 disease, 38% had high-risk cytogenetics, 32% had extramedullary disease (EMD), the median number of prior therapies was 5 (range, 2-12), and 71% had triple-class refractory MM (IMiD + PI + anti-CD38 mAb). Treatment discontinuation occurred in 108 pts (70%), most commonly due to disease progression (47%) and adverse events (14%). Among 125 pts evaluable for response, with a median follow up of 15.3 mo, the median TTNT was 8.0 mo (95% CI, 7.2-8.9) and the median PFS was 4.2 mo (95% CI, 3.7-4.9). TTNT and PFS were similar in subgroups of pts with triple-class refractory MM and EMD (Table). Subsequent therapies after melflufen + dex will be presented. Conclusions: TTNT in HORIZON (median 5 prior lines) was consistent with previous reports of TTNT in pts with RRMM who received melflufen + dex or other therapies (median 2-4 prior lines) (Bringhen et al. J Clin Oncol. 2019. Abs. 8043). Melflufen + dex is being further evaluated in the phase 3 OCEAN study (NCT03151811) in pts with RRMM who are refractory to lenalidomide. Clinical trial information: NCT02963493. [Table: see text]
Effect of local activation via SQ3370 on the safety of chemotherapy with concomitant anti-tumor immune response.
Authors: Sangeetha Srinivasan, Nathan A. Yee, Amir Mahmoodi, Michael Zakharian, Jose Manuel Mejia Oneto
Journal: Journal of Clinical Oncology (2020)

e15525 Background: With systemic chemotherapy, only 1-2% of the dose given reaches a local tumor, while the remaining leads to off-target toxicities. Hence, there is a critical need to locally deliver cytotoxics directly to the tumor. Our approach (SQ3370) consists of: 1. SQL70 - drug-activating biomaterial carrying 2. SQP33 - chemically-modified prodrug of doxorubicin (Dox) with attenuated activity. Methods: SQL70 is injected at the tumor site followed by SQP33 given systemically. The prodrug is captured by the biomaterial due to their complementary chemical reactivities. The active drug is then spontaneously released, providing local delivery directly to the tumor region while reducing systemic side effects. Results: We have shown that the greater safety of SQ3370 allows significantly higher doses to be administered compared to conventional Dox. PK studies in rodents and dogs show highly efficient capture and activation of the prodrug, likely due to the rapid reaction of SQP33 with SQL70. Without SQL70, SQP33 shows minimal spontaneous conversion to active Dox. A single SQL70 injection selectively activated multiple doses of SQP33 at the target site, maximizing the local therapeutic index. Additionally, SQP33 was capable of being activated by SQL70 injected in various regions in the body, including peri/intratumoral, intraperitoneal, subcutaneous and intramuscular sites. SQ3370 treatment also enhances efficacy in tumor-bearing mice: In a syngeneic MC38 colorectal cancer model, SQ3370 significantly improved anti-tumor response and overall survival compared to conventional Dox. In mice bearing two tumors, SQL70 injection at one tumor site followed by systemic SQP33 treatment induced an anti-tumor response in both the injected and non-injected tumors. This technology also enabled a sustained anti-tumor response upon rechallenge with MC38 tumor cells, without additional treatment. Furthermore, SQ3370 increased CD4 and CD8 TILs and decreased regulatory T-cells in both injected and non-injected tumors, suggesting that SQ3370 can induce an immune-mediated anti-tumor effect, thus expanding potential treatment options in the clinic and highlighting the advantages of immune-sparing cytotoxic therapy. Conclusions: SQ3370 enables delivery of cytotoxic drugs to multiple target sites while limiting off-target exposure, leading to improved safety and efficacy. A multicenter, first-in-human, Phase 1 dose-escalation clinical trial (NCT04106492) in patients with advanced solid tumor malignancies is planned to commence enrollment in April, 2020.
Clinical characteristics, esophageal motility and acid exposure in elderly patients with gastroesophageal reflux disease
Authors: Yan-xiang Pei, Zhan-min Shang, Jian-yu Hao, Wan-nong Huang
Journal: BMJ (2012)

Objectlve To review the clinical characteristics,esophageal motility and acid exposure in elderly patients with gastroesophageal reflux disease (GERD).Methods Two hundred and sixty patients aged 18 -81 years were diagnosed as gastroesophageal reflux disease from 2005 to 2011 in outpatient clinic,the patients were divided into elderly group ( ≥ 60 y) and control group ( ＜ 60 y).The incidence of esophagitis,severity of esophagitis,esophageal motility and esophageal acid exposure were analyzed and compared between two groups.Results The incidence of esophageal hiatal hernia,non-typical reflux symptoms and extra-esophageal symptoms in elderly group were higher than that of control group(45.1％ vs.30.6％,36.3％ vs.27.2％ and 37.1％ vs.25.2％,P =0.016,0.005 and 0.037,respectively).There was no significant difference in esophagitis incidence between two group (55.8％ vs.50.3％,P =0.250).The incidence of esophagitis graded as LA-B to LA-D were higher in elderly group( 19.5％ vs.10.2％ and 8.8％ vs.2.7％,P =0.034 and 0.030,respectively).The percentage of upright acid clearance time,supine reflux time of pH ＜4 and the DeMeester score of elderly group were higher than those of control group (P =0.000,0.006 and 0.001,respectively).Lower esophageal sphincter pressure (LESP) of elderly group was lower than that of control group ( 13.36 ±6.39 vs.15.57 ±7.01,P =0.009).Conclusion In comparison with young and middle-aged patients,the elderly GERD patients have lower esophageal motility,longer esophageal acid exposure time and higher frequency of severer esophagitis.

Key words: 
Gastroesophageal reflux; Esophageal pH Monitoring; Retrospective studies
CX-2029, a PROBODY drug conjugate targeting CD71 (transferrin receptor): Results from a first-in-human study (PROCLAIM-CX-2029) in patients (Pts) with advanced cancer.
Authors: Melissa Lynne Johnson, Anthony B. El-Khoueiry, Navid Hafez, Nehal J. Lakhani, Hirva Mamdani, Jordi Rodon Ahnert, Rachel E. Sanborn, Thang Ho, Rachel Li, Jana Waldes, Alexander I. Spira
Journal: Journal of Clinical Oncology (2020)

3502 Background: CX-2029 is a PROBODY drug conjugate (PDC) of MMAE, a potent microtubule inhibitor, directed against CD71 (transferrin receptor 1). In addition to being an abundant tumor antigen, CD71 is highly expressed on normal cells, precluding targeting by a traditional antibody drug conjugate (ADC). PDCs are masked ADCs, unmasked predominantly by tumor-associated proteases, thereby restricting target engagement to tumors. Both a CD71 PDC and ADC displayed broad activity in multiple xenograft tumor models; in toxicology studies, the PDC was tolerable at doses consistent with efficacy in non-clinical tumor models while the ADC was not. Methods: In a phase 1/2 first-in-human study of PDC CX-2029 in advanced solid tumors (N CT03543813 ), pts with ECOG 0–1 and ≥1 prior systemic therapy were enrolled into escalating dose cohorts of the PDC CX-2029 given IV every 21 days. Endpoints included evaluation of MTD, safety, antitumor activity, and potential biomarkers; plasma and tissue samples were collected for PK/PD analyses. Preliminary results are reported. Results: As of 30 November 2019, 34 pts were enrolled (median age 59 y; 59% male; 71% ECOG 1; median [range] of 3 [1–16] prior therapies). Pts received a median of 3 (1–12) CX-2029 doses. Starting dose for escalation was 0.1 mg/kg. Following a single CX-2029 dose, median molar ratio of masked CX-2029 to total CX-2029 for AUC tau was 0.938 (0.864–0.942); the ratio of free MMAE to total CX-2029 was &lt;0.03. Infusion-related reactions were the most common treatment-related AE (TRAE) of any grade (88%; primarily low grade and with first infusion), followed by anemia (56%), fatigue and nausea (24% each), neutropenia (21%), and leukopenia (12%). Grade 3+ TRAEs in ≥10% pts were anemia (35%) and neutropenia (18%). In 32 response-evaluable pts, 1 pt had a confirmed partial response (squamous NSCLC); 9 had stable disease including 1 pt with ocular melanoma treated for 36 weeks. Conclusions: The observed safety profile for CX-2029 effectively reduces on-target toxicity for this previously undruggable target, supporting the PROBODY platform. Evidence of anti-tumor activity was observed. Dose escalation continues. Clinical trial information: NCT03543813 .
Blood lipid, glucose and uric acid levels in patients with chronic spontaneous urticaria
Authors: Ruifeng Sun, Jing Qi, Shi Lian
Journal: BMJ (2016)

Serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), uric acid (UA) levels and fasting blood glucose (FBG) were measured in 67 patients with chronic spontaneous urticaria(CSU) and 66 healthy subjects (controls). Results showed that the rates of increased serum TG and FBG levels in CSU patients were higher than those in controls (19% vs. 6%, χ2=5.309, P 0.05). The rate of rising FBG in CSU patients accompanied by angioedema(4/9)was higher than that in CSU patients without angioedema(7%, χ2=7.181, P<0.05).


Key words: 
Urticaria, chronic; Dyslipidemias