tbuckley/cabot-search huggingface dataset:
Abstract 15794: Changes in Patient and Caregiver Depression and Anxiety Post-implantation of a Ventricular Assist Device
Authors: Julie T Bidwell, James O Mudd, Jill M Gelow, Karen S Lyons, Shirin O Hiatt, Christopher V Chien, Kathleen L Grady, Christopher S Lee
Journal: Circulation (2015)

Introduction: The impact of ventricular assist device (VAD) therapy on affective symptoms among patients with advanced heart failure (HF) and their informal caregivers is not well understood. Hypothesis: We hypothesized that patients’ affective symptoms would improve post-implant, while caregivers’ affective symptoms would worsen. Methods: Prospective, longitudinal data was collected on patients and their caregivers (n=25 dyads) prior to and at 30 and 90 days after VAD implantation. Depression was measured using the Patient Health Questionnaire-8 (PHQ-8; range 0-24, higher scores indicate worse depressive symptoms), and anxiety was measured using the Anxiety Scale of the Brief Symptom Inventory (BSI-ANX; range 0-4; higher scores indicate worse anxiety) in patients and their caregivers. Pre vs. post VAD comparisons in affective symptoms were examined using paired t-tests. Results: Patients requiring VAD implantation were 54.9±12.5 years of age and mostly male (84.0%), while caregivers were 53.9±11.1 years of age and mostly female (80.0%); a majority (72.0%) of dyads were spouses. Patient depression decreased significantly from pre-implant (9.3±5.6) to 30 days (6.9±5.4; t=2.2, p=0.04) and 90 days post-implant (3.6±3.6; t=5.3, p&lt;0.01); patient anxiety also decreased from pre-implant (1.0±0.9) to 30 days (0.5±0.7; t=2.9, p&lt;0.01) and 90 days post-implant (0.3±0.4; t=4.5, p&lt;0.01). In contrast, there were no significant changes in caregiver depression from pre-implant (6.0±5.2) to 30 days (5.2±4.4; t=0.5, p=0.6) and 90 days post-implant (6.6±5.7; t=-0.4, p=0.7) or in caregiver anxiety from pre-implant (0.8±0.6) to 30 days (0.5±0.4; t=1.5, p=0.2) and 90 days post-implant (0.6±0.7; t=0.9, p=0.4). Conclusions: Although depression and anxiety improved dramatically for patients after VAD implantation, the pre-implant affective symptom burden of caregivers was substantially higher than national norms at baseline and was not ameliorated over time. As patient symptoms improve with VAD therapy, their caregivers may benefit from psychosocial interventions to address protracted symptoms of depression and anxiety.
Multimodal treatment choice and feasibility in older patients with resectable gastric cancer: a multicentric cohort study.
Authors: Helene Boussion, Florence Canoui-Poitrine, Philippe Caillet, Christophe Louvet, Marie-Line Garcia, Thierry Andre, Isabelle Baumgaertner, Benoit Rousseau, Iradj Sobhani, Marie Chaubet-Houdu, Francesco Brunetti, Elena Paillaud, Christophe Tournigand
Journal: Journal of Clinical Oncology (2016)

e15528 Background: The average age of patients (pts) diagnosed with gastric cancer (GC) is 69 yrs. In resectable GC, multimodal approach is the standard of care but its choice and feasibility in unknown in older pts. The aim is to assess the choice and feasibility of the whole strategy in this population in real-life setting. Methods: Consecutive pts age ≥ 70 yrs with resectable GC (including oesogastric junction) and eligible for curative treatment were retrospectively included in three teaching hospitals from 2007 to 2014. Endpoints were initial treatment choice and feasibility measured by : optimal treatment completion defined as surgery with perioperative treatment or surgery followed by adjuvant treatment or surgery alone for stage I ; CTCAE grade 3-4 toxicities and post-operative complications. Associated factors were identified by uni and multivariate analysis. Results: 189 consecutive pts (median age 77yrs (70-95)) were included. 45.7% had peri-operative strategy, 9.2% surgery with adjuvant treatment, 27.2% surgery alone (including 28% stage I), and 17.9% systemic treatment alone. Overall, optimal treatment was performed in 47%. 53.9% had post-operative complications and 30.8% had grade 3/4 toxicities. By multivariate analysis, age ≥ 80 yrs was associated with less likely perioperative treatment choice (p = 0.009). Increase age (p = 0.01), depressive mood (p = 0.04) and not-living at their personal home (p = 0.03) were independently associated with less likely optimal treatment. Number of severe comorbidities (p = 0.04), medications (p = 0.03) and oesogastric junction location (p = 0.001) were independently associated with post-operative complications. Independent associated factors for neoadjuvant and adjuvant treatments non completion were malnutrition (p = 0.04), referral for a geriatric assessment (p = 0.01) and anemia (p = 0.01). Conclusions: Optimal multimodal treatment for GC is feasible for older pts but post-operative morbidity and treatment toxicities are frequent and should not be underestimated. Chronological age influenced the choice of treatment plan whereas several geriatric factors are associated with feasibility.
Clinico-pathological and molecular characterisation of <i>BRAF</i> mutant metastatic colorectal cancer (mCRC): Are all mutations created equal?
Authors: Marta Schirripa, Paola Biason, Francesco Cortiula, Maria Simona Pino, Federica Urbano, Carlotta Antoniotti, Salvatore Corallo, Fabio Gelsomino, Armando Orlandi, Giada Munari, Umberto Malapelle, Massimo Rugge, Claudia Mescoli, Luca Reggiani Bonetti, Giovanni Lanza, Angelo Paolo Dei Tos, Giovanna De Maglio, Vittorina Zagonel, Fotios Loupakis, Matteo Fassan
Journal: Journal of Clinical Oncology (2018)

3590 Background: Functional studies on preclinical models (Yao, Nature 2017) identified 3 classes of BRAF mutations: activating RAS-independent BRAF mutations signaling as monomers (class 1-BRAF V600E) or as dimers (class 2-codons 601/597) and RAS-dependent BRAF mutations with impaired kinase activity (class 3-codons 594/596). While clinico-pathological and molecular features of class 1 mutation are well known, limited data are available with regard to class 2 and 3 mutations, due to their rarity in CRC. Methods: Clinico-pathological, molecular and outcome data from BRAF mutated mCRC patients were collected. A group of BRAF wild-type (wt) patients was included as control. IHC analyses were performed to determine the consensus molecular subtypes (CMS). Clinical features were compared by chi-square or fisher’s exact test. PFS and OS were evaluated by Kaplan-Meier and log-rank test. Results: Class 1, 2 and 3 included 92, 12 and 13 patients respectively. BRAF wt patients were 540. No clinico-pathological differences were observed comparing class 1 to class 2 BRAF mutated. Conversely, BRAF class 3 mutated were more frequently left sided (p = 0.0028), well differentiated (p = 0.0120), pN0 (p = 0.0159), and with no peritoneal metastases (p = 0.0176) compared to class 1. With regard to CMS, class 2 and 3 tumors were all assigned to CMS2-3. Class 1 tumors were assigned to CMS1, 2 or 3 in 39%, 44% and 17% of cases. Outcome results are reported in the Table below. Conclusions: Our data confirm previous findings describing specific features associated with BRAF rare mutations. For the first time clinico-pathological characteristics and outcome data are reported according to the 3 classes categorization of BRAF mutations. In particular, class 1 and 2 share similar features and worse outcome compared to class 3 and wt patients. Overall Survival Progression Free Survival Median (months) HR (95% CI) p-value Median (months) HR (95% CI) p-value BRAF wild type (N = 540) 42.2 - < 0.0001 10.1 - < 0.0001 BRAF mutant class 1 (N = 92) 21.0 2.38 (1.61-3.54) 7.3 2.02 (1.39-2.94) BRAF mutant class 2 (N = 12) 23.4 1.90 (0.85-4.26) 7.0 2.49 (0.92-6.74) BRAF mutant class 3 (N = 13) 44.5 0.93 (0.51-1.69) 13.8 0.85 (0.47-1.54)
Rose geranium in sesame oil nasal spray: A potential treatment for nasal vestibulitis?
Authors: Elizabeth Jane Cathcart-Rake, Gaurav Goyal, DeAnne Renee Smith, David Zahrieh, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2018)

e22166 Background: Nasal vestibulitis is an infrequently described side effect of cancer-directed therapy, with new observations suggesting that it is a relatively frequent problem. A rose geranium in sesame oil spray product anecdotally appears to improve nasal vestibulitis symptoms. Methods: Patients with breast cancer prescribed rose geranium nasal spray were evaluated regarding their use of this product, whether it improved symptoms, the degree of benefit, and any unpleasant effects of the nasal spray. Patients were identified by pharmacy records. Medical records of those patients who provided HIPPA clearance for medical chart inquiry were reviewed to determine patient demographic and medical information, as well as to define cancer treatment regimens and documentation of symptoms. Questionnaires were sent to patients regarding their experiences. Results: Of the 40 patients with breast cancer who were prescribed rose geranium nasal spray for nasal symptoms, 100% were receiving cancer-directed therapy: 66% were receiving chemotherapy, most frequently with taxanes, and 73% were receiving targeted therapy, most frequently with HER2-directed therapies. Twenty-one patients returned surveys, of which 20 had used the spray product. Nasal symptoms and nasal spray use, efficacy, and toxicity data are provided in the table. Conclusions: These results support, but do not prove, that rose geranium in sesame oil nasal spray improves patient-reported nasal symptoms associated with cancer-directed therapy. Further evaluations are needed to determine efficacy of rose geranium in sesame oil nasal spray. Table 1. Survey Responses. Survey Items Patients (%) Symptom (N = 21) Dryness 18 (86) Pain 17 (81) Bleeding 19 (90) Scabbing 14 (67) Sores 11 (52) Frequency of spray use (N = 21) Never 1 (5) Once 0 (0) A few times 1 (5) Weekly 0 (0) Daily 10 (48) Several times a day 9 (43) Nasal spray helped symptoms (N = 20) Yes 20 (100) No 0 (0) Magnitude of symptom improvement with spray (N = 20) Little 1 (5) Moderate 11 (55) Dramatic 6 (30) Resolved symptoms 2 (10) Experienced unpleasant effects from spray (N = 20) Yes* 2 (10) No 18 (90) *“oily coating at the back of the throat,” “messy”
A threshold of clinically significant reduced PTEN expression in melanoma.
Authors: Brooke E Rosenbaum, Keith Michael Giles, Yang Li, Sung Won Han, Eric Michael Robinson, Una Moran, Judy Zhong, Richard L. Shapiro, Farbod Darvishian, Iman Osman
Journal: Journal of Clinical Oncology (2016)

e21063 Background: Current AJCC staging criteria provide limited prognostic value for stage III melanoma patients, who have a 50% chance of recurrence. Complete loss of PTEN expression is known to be associated with worse survival in melanoma patients. Nevertheless, mouse models indicate a functional continuum for the impact of reduced PTEN levels on carcinogenesis. We aimed to define the threshold at which reduced PTEN expression becomes clinically and biologically significant. Methods: Initial stage III melanoma patients who were prospectively accrued in the NYU melanoma biorepository database ( > 2y FU, sufficient tumor material) were identified. PTEN expression was assessed using IHC (PTEN D4.3 Ab) and scored based on intensity and distribution, classifying tumors into absent, weak, intermediate, and strong groups. Log rank testing assessed differences in overall survival (OS) among groups. Multivariate Cox regression analysis tested the association between PTEN expression and OS. Following titrated PTEN knockdown in melanoma cell lines (wild-type PTEN), we quantified Akt activation by immunoblotting. Results: Of 190 cases studied, 21 (11%) had strong, 51 (27%) intermediate, 44 (23%) weak, and 74 (39%) had absent PTEN expression. No OS differences were observed between absent and weak (p = 0.99), nor intermediate and strong (p = 0.99) groups. Therefore, tumors were stratified into low (n = 72) and high (n = 118) PTEN expression groups. OS was significantly longer in patients whose tumors had high PTEN compared to those with low PTEN (p = 0.01). In multivariate analysis, high PTEN was associated with significantly longer OS than low PTEN (HR 0.47, p < 0.01), controlling for primary tumor thickness, ulceration, tumor substage and adjuvant therapy. Immunoblotting showed dose-dependent activation of Akt which correlated with the degree of PTEN knockdown in melanoma cell lines. Conclusions: Our data support the continuum model in which reduced PTEN expression confers increased Akt activation in melanoma. Further, it identifies a threshold of reduced PTEN expression, between low and intermediate levels, beyond which the clinical impact is identical to that of complete PTEN loss.
Prognosis of triple negative breast cancer patients who attain pathological complete response with neoadjuvant carboplatin/docetaxel and do not receive adjuvant anthracycline chemotherapy.
Authors: Priyanka Sharma, Bruce F. Kimler, Claire Ward, Anne O'Dea, Marc Steven Hoffmann, Jennifer R. Klemp, Marilee McGinness, Jamie Lynn Wagner, Joshua Mammen, Amanda Leigh Amin, Carolyn Lehn, Roy A. Jensen, Andrew K. Godwin, Qamar J. Khan
Journal: Journal of Clinical Oncology (2016)

1015 Background: Pathological complete response (pCR) in TNBC is associated with excellent long term survival. Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pCR in TNBC. The prognostic value of pCR attained with anthracycline-free platinum/taxane chemotherapy in TNBC is not well known. Aims: To determine the long term outcomes in TNBC patients treated with NA Cb + Docetaxel (D). Methods: 443 patients with stage I (T>1cm), II, or III TNBC were enrolled in a prospective multisite registry between 2011-2015, out of which 76 patients received NA chemotherapy regimen of Cb(AUC 6) + D(75 mg/m2) q 21 days (4-6 cycles). pCR (no evidence of invasive tumor in the breast and axilla) and Residual Cancer Burden (RCB) was evaluated and patients were followed for recurrence and survival. Results: For the 76 eligible patients, median age: 52 yrs, African-American:16%, median tumor size: 3 cm, 33% LN positive and 25% with germline BRCA mutation. 88% of patients received 6 cycles of chemotherapy. pCR and RCB 0/1 rates were 66% (50/76) and 80% (61/76) respectively. Patients achieving pCR did not receive additional adjuvant chemotherapy. 73% of patients with RCB 2/3 received adjuvant chemotherapy. At a median follow up of 2.3 (range 0.5 - 7.8) years the RFS is 88% in the entire cohort. RFS is 95% and 76% in patients with and without pCR, respectively (HR: 0.14, p=0.014) and 94% and 68% in patients with RCB 0/1 and RCB 2/3 respectively (HR: 0.19, p=0.029). On univariate analysis higher stage, node positive status and lack of pCR were associated with a worse RFS. BRCA mutation status did not impact pCR or RFS Conclusions: NA CbD chemotherapy yields encouraging pCR rates (66%) in patients with TNBC; patients achieving pCR with this regimen demonstrate excellent RFS (95% at 2.3 years) without adjuvant anthracycline chemotherapy. The RFS of 76% in patients without pCR is consistent with known literature. For TNBC patients achieving pCR with NA CbD, adjuvant anthracycline can be avoided. Prospective studies to evaluate the efficacy of neoadjuvant platinum + taxane regimen in TNBC are needed.
Integration of comlementary and integrative medicine into palliative care of patients with advanced cancer.
Authors: Ayelet Shai, Noah Samuels, Eran Ben Arie
Journal: Journal of Clinical Oncology (2016)

10028 Background: The use of complementary and integrative medicine (CIM) is widespread among patients with cancer, often being used as adjunct to palliative treatment in incurable disease. We sought to characterize patients with advanced, incurable cancer who were referred to a CIM treatment program provided within a community-based oncology service, and to study the association between adherence to CIM and survival. Methods: Patients with metastatic cancer defined as “incurable” by the treating oncologist, who had been referred by their oncologist, nurse or psycho-oncologist to an integrative physician (IP) for consultation, were eligible for study inclusion. After assessing quality of life-related concerns, a patient-tailored CIM treatment program was designed. Adherence to CIM treatment was defined as attending at least 4 weekly CIM sessions, with no more than 30 days between each. Demographic data were recorded at baseline, and oncologic data including performance status (PS), line of therapy, type of therapy and duration of response extracted from patients' files. Survival data were taken from the CHS database. Results: A total of 159 patients participated in the study, 66.7% of them female. Median age was 63.9 years. 68.5% of patients commenced CIM treatment during their first-line regimen. Anti cancerous therapy consisted of chemotherapy in 88.1% of patients, and 58.9% responded for more than 6 months. Treatment goals at CIM initiation included fatigue (reported by 85% of patients), gastrointestinal concerns (58.1%), pain (52%) and emotional distress (58.1%). A total of 56.6% of patients were defined as adherent to the CIM treatment program, with similar demographic and clinical variables to those of the non-adherent patients. The median survival for the entire group was 16 months. Patients who had a PS of 1-2 seemed to have inferior survival rates when compared to those with a PS of 0 (HR 2.295; 95% CI 0.931-5.567; p = 0.071). Adherence to CIM was not related to survival. Conclusions: CIM treatments can be integrated into the supportive and palliative care of patients with incurable cancer. Adherence to CIM treatment may be evident in more than half of the patients in this setting.
Pazopanib in metastatic osteosarcoma patients: Report of 9 cases treated off label at Rizzoli Orthopedic Institute.
Authors: Alessandra Longhi, Anna Paioli, Marilena Cesari, Emanuela Palmerini, Massimo Abate, Elisabetta Setola, Michele Rocca, Maria Cristina Salone, Davide Maria Donati, Stefano Ferrari
Journal: Journal of Clinical Oncology (2018)

e23501 Background: Osteosarcoma is a rare disease recurring mainly to the lungs. In unoperable cases high dose ifosfamide, gemcitabine/docetaxel, /etoposide are employed. Very few studies are available for those patients who failed the second or further line of chemotherapy for advanced disease. Pazopanib is an oral multitargeting tyrosine kinase receptor inhibitor that targets VEGFR-1,-2,-3, PDGFR-α,-β, M-CSF receptor/fms, and SCFR/c-kit, as well as B-Raf approved for treatment of advanced soft tissue sarcoma. A series of 3 cases reported activity of pazopanib in advanced osteosarcoma. Other studies with pazopanib and other TKI (Lenvatinib) in advanced osteosarcoma are ongoing. Methods: On a named patient program basis, 9 patients with advanced unoperable progressive osteosarcoma received Pazopanib after failure of the currently used further line of chemotherapy. All patients had PET CT and CT of the chest before treatment. Pazopanib was administrated at a dose of 800 mg/d orally. Response to treatment, according to RECIST 1.1 was set every 2 months. Results: Nine patients were enrolled from February 2017 to October 2017. Median age was 20 years (range 12-53), Sex M:F = 5:4. Metastatic site were lung in 8, bone+lung in one. Toxicity: A dose-reduction of Pazopanib ( 600mg or 400 mg) was performed in all but one patient due to toxicity:Hand-foot syndrome (2 ) , hypertension (2 ) , G3-4 thrombocitopenia (2 ), pneumothorax (1), dizziness (1) , diarrhea (1), nausea (1) .One patient of 53 had an intracranial hemorrhage after 45 days of treatment due to uncontrolled hypertension, but recovered without residual neurological impairmentand she's not evaluable for response After a median follow up of 5 ms (3-9) eight patients are evaluable for response: 3/8 (37.5% ) patients had Partial Response of 6, 6 and 5 months duration; 3/8 patients had stable disease of 6, 4, 2 months duration, 2 had progression disease after 2 months (see table). Conclusions: Pazopanib treatment in advanced osteosarcoma patients was feasible and well tolerated 3 out of 8 evaluable pts reached a partial response in a heavily pretreated setting. These promising results are worthy of further larger studies.
PD-L1 expression and possibility of its therapeutic target in cutaneous angiosarcoma.
Authors: Kyoichi Kaira, Akira Shimizu, Masahito Yasuda, Yuko Ohkubo, Takayuki Asao, Kenzo Takahashi, Osamu Ishikawa
Journal: Journal of Clinical Oncology (2016)

e23110 Background: Programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) targeting therapy have shown a promising survival benefit for patients with several human neoplasms. Cutaneous angiosarcoma (CA) is extremely rare neoplasma with a dismal outcome regardless of any treatments. However, it remains unclear whether the expression of PD-L1 is associated with any clinical and pathological variables in patients with CA. The aim of this study is to evaluate the clinicopathological significance of PD-L1 expression in CA. Methods: A total of 52 patients with CA patients were retrospectively reviewed. PD-L1, tumor proliferation determined by Ki-67 index and microvessel density determined by CD34, was evaluated immunohistochemically and correlated with the clinicopathological variables. Results: PD-L1 was positively expressed in 40% (21/52) of CA. The expression of PD-L1 was significantly associated with tumor cell proliferation determined by Ki-67 labeling index. Multivariate analysis confirmed that the positive expression of PD-L1 was identified as an independent factor to predict worse outcome. Conclusions: PD-L1 expression is a novel pathological marker for predicting worse outcome in CA patients. The inhibition of PD-L1 function may prevent tumor growth, providing us with a new effective therapeutic target of CA in future.
Labeling Changes and Costs for Clinical Trials Performed Under the US Food and Drug Administration Pediatric Exclusivity Extension, 2007 to 2012
Authors: Michael S. Sinha, Mehdi Najafzadeh, Elizabeth K. Rajasingh, James Love, Aaron S. Kesselheim
Journal: JAMA Internal Medicine (2018)

Pharmaceutical manufacturers can receive 6 additional months of market exclusivity for performing pediatric clinical trials of brand-name drugs widely used in adults. Congress created this incentive in 1997 because these drugs were being used off-label in children without such trials.To review updates to drug labeling and the cost to consumers of extending market exclusivity related to the pediatric exclusivity program.From government records, we identified 54 drugs that earned the pediatric exclusivity incentive between 2007 and 2012. We evaluated labeling changes from the pediatric studies. We then extracted trial details from clinical review documents and used industry estimates of trial costs on a per-patient basis to estimate cost of investment for trials (with a 10% cost of capital). To calculate the net return and cost to consumers during the 6-month exclusivity period, we estimated additional revenue for the 48 drugs with available information.For each drug, we evaluated labeling changes and costs associated with pediatric trials under the Best Pharmaceuticals for Children Act and the cost to consumers of 6-month market exclusivity extensions.The 141 trials in our sample enrolled 20 240 children (interquartile range [IQR], 2-3 trials and 127-556 patients per drug). These trials led to 29 extended indications and 3 new indications, as well as new safety information for 16 drugs. Median cost of investment for trials was $36.4 million (IQR, $16.6 to $100.6 million). Among 48 drugs with available financial information, median net return was $176.0 million (IQR, $47.0 million to $404.1 million), with a median ratio of net return to cost of investment of 680% (IQR, 80% to 1270%).Clinical trials conducted under the US Food and Drug Administration's pediatric exclusivity program have provided important information about the effectiveness and safety of drugs used in children. The costs to consumers have been high, exceeding the estimated costs of investment for conducting the trials. As an alternative, policymakers should consider direct funding of such studies.