tbuckley/cabot-search huggingface dataset:
A phase II, single arm clinical trial involving an alternative cancer treatment psorinum therapy in patients with metastatic bladder cancer.
Authors: Aradeep Chatterjee, Sudin Bhattacharya, Ashim Kumar Chatterjee, Amitava Chakraborty, Radhe S. Bhakta, Jaydip Biswas
Journal: Journal of Clinical Oncology (2013)

e15520 Background: We prospectively studied the clinical efficacy of an alternative cancer treatment “psorinum therapy” in treating metastatic bladder cancer (MBC). Methods: Our study was phase II, open level, single arm and single stage. Participants’ eligibility criteria included (1) pathological confirmation of the malignancy (2) metastatic disease status (3) no prior conventional cancer treatments (4) Karnofsky performance status between 40- 70%. The primary outcome measures of the study were (1) to assess the radiological tumor response rate (using CT scanning procedure and following the RECIST criteria); (2) to assess how many participants survived at least 1 yr, 2yrs, 3yrs, 4yrs and finally, after 5 yrs of the study. The secondary outcome measure was to assess the side effects of the investigational anti- cancer drug (psorinum) if any. Psorinum (an alcoholic extract of scabies slough and pus cells) was administered orally at a dose of 0.04ml/ Kg body weight/ day as a single dose on an empty stomach for a complete course duration of 2 yrs to all the participants along with allopathic and homeopathic supportive cares. Results: 72 participants included in the final analysis at the end of the study. According to the RECIST criteria, complete response occurred in 6 (8.33%) cases and partial response occurred in 25 (34.72%) cases. 55 (76.39%) of them survived at least 1yr, 42 (58.33%) survived at least for 2yrs, 28 (38.89%) survived at least 3yrs, 23 (31.94%) survived at least 4yrs, 17 (23.61%) survived at least 5yrs. These participants didn't received conventional or any other investigational cancer treatments. Conclusions: The results of the study show clinical efficacy of psorinum therapy in treating patients with MBC. The investigational drug psorinum is non- toxic. Randomized controlled clinical trial should be conducted for further investigation of this alternative cancer treatment in treating metastatic bladder cancer to integrate it into the mainstream of oncology treatments.
Socioeconomic impact of breast cancer survivors.
Authors: Hideko Yamauchi, Atsuko Kitano, Takashi Fukuda
Journal: Journal of Clinical Oncology (2014)

e20611 Background: Cancer and its treatments largely affect socioeconomy of community. Support system for working cancer patients is urgently required in the world. In Japan, the prevalence of breast cancer by age is higher in younger women than in western countries. About half of breast cancer patients were diagnosed in 30-50’s. Since they are considered most productive working force in society, it is urgent to investigate work loss by the disease and its treatment for cancer survivors and to develop interventions to minimize it. Methods: To assess the impact of breast cancer to socioeconomic status of survivors, we conducted survey in them who had registered to an internet-based patient care monitor system. We also estimate work loss from other cancers. Results: Among 100 breast cancer survivors registered in the monitor system who worked at the time of diagnosis, only 53% of them remained in the same job after diagnosis of breast cancer. Most influential factors to work status changes are fatigue, loss of motivation for working and stress on working. The average work-days lost within one year after breast cancer diagnosis was 79.7 days. Based on Japanese Health Ministry of Health, Labor and Welfare database, we estimated total economic loss due to hospital visits for cancer treatment, $1,569 million (exchange rate: $1=100 yen) for women and $2,959 million for men. Breast cancer is estimated as the number one cause of economic loss among cancer survivors in Japan and the loss is estimated $551 million. Considered work loss out of hospital visits, we estimated economic loss as $491 million from the survey results. Total economic loss due to breast cancer is estimated about $1 billion for society. Conclusions: We noted that cancer diagnosis causes enormous impact for socioeconomy. Surprisingly, breast cancer is estimated as one of the most influential cause of economic loss from cancer diagnosis in Japan. It is required to establish support system for working cancer survivors urgently. We currently investigate interventions to minimize work loss from cancer. (This work is supported by a Grant-in-Aid for Cancer Research from the Japanese Health Ministry of Health, Labor and Welfare, H24-Ganrinsho-ippan-011).
Outcomes in financially disadvantaged patients with breast cancer in south India.
Authors: Jayanti Satish Thumsi, Mallika Nataraj, Kavitha M L, Sachin Suresh Jadhav
Journal: Journal of Clinical Oncology (2014)

e17501 Background: Economic disparity affects the treatment and hence the outcome of malignancies. We for the first time in India have attempted to quantify the effect of inadequate financial resources on the outcome of patients with breast cancer who have visited our center. Methods: Retrospective and prospective data collection was done for all the patients who visited the breast cancer clinic of Global Cancer Institute, Bangalore, between January 2012 and August 2013. Affordability for treatment is decided during the first patient visit as availability of about Rupees 400,000 which is deemed to be sufficient for appropriate multidisciplinary treatment. Events were defined as death and relapse. Results: 119 were diagnosed to have breast cancer in this time period. The median age was 51 years (range 17-84 years). 57 (47.9%) did not have adequate funding for treatment. Greater number of non-affording patients had less comorbidities, more extensive intraductal component (5.26% vs. 1.61%, p=0.028) and perinodal spread (70.4% vs 33.3% , p=0.009). A greater number of patients who had limited funding received ≤6 cycles of FAC (5-FU, adriamycin and cyclophosphamide) (57.7% vs. 17.6%, p=0.000) as opposed to 8 cycles of Epirubicin Cyclophosphamide/Adriamycin Cyclophosphamide with Docitaxel/Paclitaxel (7.7% vs. 47.1%, p=0.000). Among the non-affording and affording patients, the 2-year overall survival was 91.7% ± 8% vs 93.9% ± 4.2% (p=0.498), the 2-year event-free survival was 28.9% ± 21.7% vs 94.3% ± 3.9% (p=0.049) and the 2-year relapse-free survival was 32.2% ± 23.9% vs. 97.4% ± 2.6% (p=0.024), respectively. Conclusions: Economic disparity has a statistically significant decrease in the relapse-free and event-free survival in patients with breast cancer in South India primarily due to poor risk disease and differences in chemotherapy.
Dietary Omega-3 Fatty Acid Supplementation Improves Sickle Cell Bone Disease By Affecting Osteoblastogenesis and Adipogenesis
Authors: Maria Teresa Valenti, Luca Dalle Carbonare, Alessandro Mattè, Lorenzo Anez-Bustillos, Mark Puder, Samuele Cheri, Michela Deiana, Enrica Federti, Serge Cedrick Toya Mbiandjeu, Angela Siciliano, Carlo Brugnara, Lucia De Franceschi
Journal: Blood (2018)
Depressive symptoms linked to social media use are higher among girls
Authors: Harriet Pike
Journal: BMJ (2019)

Evidence linking social media use and depressive symptoms has emerged from a study of 14 year olds, with the connection being stronger for girls than boys.

The study, published in EClinicalMedicine , showed that, among teenage girls, greater use of social media corresponded with a stepwise increase in depressive symptoms.1 For boys, higher depressive symptoms were seen among those reporting three or more hours of daily social media use.

Online bullying and poor sleep were linked with greater use of social media and were responsible for the low mood seen among both sexes, the researchers concluded.

The study looked at associations between social media use and depressive symptoms and analysed data from …
Evaluating the prognostic significance of visceral pleural invasion in stage IB non-small cell lung cancer that is less than or equal to 3 cm.
Authors: Rosa Nouvini, Roger Keresztes, Jie Yang, Jiawen Zhu
Journal: Journal of Clinical Oncology (2014)

e18519 Background: Stage IB non-small cell lung cancer (NSCLC) with visceral pleural invasion (VPI) is felt to be a high risk cancer that may benefit from adjuvant chemotherapy. We hypothesize that stage IB NSCLC </=3cm with VPI carries no greater risk and has the same prognosis as stage IA NSCLC. Methods: A retrospective analysis on 149 patients with stage IA NSCLC and 32 patients with stage IB NSCLC </= 3cm with visceral pleural invasion during 1999-2012 was conducted at Stony Brook University Hospital. There were 53.42% females and 46.58% males in the stage IA group and 57.14% females and 42.86% males in the stage IB group. Five of the 32 stage IB patients received adjuvant chemotherapy and the rest were treated with resection alone. The age for IA patients was 66.32+/- 9.81 years and 63.09+/- 8.96 years for IB patients. Overall survival (OS) was defined from the time of surgery to death or his/her last follow up date. Kaplan-Meier analyses and log-rank statistics were used to estimate and compare OS. Similar analyses were conducted on tumor size </= 2cm. Statistical significance was set at 0.05 and analysis was performed using SAS 9.3. Results: There was no significant difference in OS in both groups </=3cm (P-value =0.3561). The OS rates of stage IA and IB at 3 years after surgery were 82.79% (95% CI:75.38- 88.14%) and 86.99% (95% CI: 64.44- 95.68%), respectively. At 5 years after surgery the OS rates for stage IA and IB were 69.84% (95% CI: 60.25 -77.54%) and 48.93% (95%CI: 14.47-76.78%), respectively. When comparing tumors in both groups </= 2.0cm there was no significant difference in OS (P-value=0.8727). At 3 years after surgery, OS of IA and IB were 83.11% (95% CI: 73.47-89.49%) and 94.12% (95% CI: 65.02-99.15%), respectively. After five years of surgery for this group, OS was 65.52% (95% CI: 52.60-75.72%) and 62.75% (95% CI: 7.11- 92.11%), respectively. Conclusions: There is no statistically significant difference in the overall survival between stage IA NSCLC and stage IB NSCLC </=3cm and <=2cm with VPI, therefore VPI should not be the sole determinant for using adjuvant chemotherapy.
Quality of Life in Chronic Myeloid Leukemia Patients with Deep Molecular Response Who Stopped Therapy By Tyrosine Kinase Inhibitors: Interim Results of Russian Prospective Multicenter Trial RU-SKI
Authors: Anna Petrova, Ekaterina Chelysheva, Oleg Shukhov, Anastasiya Bykova, Galina Gusarova, Irina Nemchenko, Nikolay Tsyba, Anna G Turkina, Tatiana Nikitina, Natalia Porfirieva, Anna Zinkovskaya, Tatiana Ionova
Journal: Blood (2018)
Are new drugs more expensive than old ones? Trends in the benefit-adjusted launch prices of anticancer drugs, 1995-2013.
Authors: David H. Howard, Rena M. Conti
Journal: Journal of Clinical Oncology (2014)

6525 Background: Media reports have fueled the perception that anticancer drugs’ launch prices have increased over time, but these typically rely on inaccurate measures of prices, focus on a few high-profile drugs, and do not adjust for benefits. We evaluate trends in drugs’ benefit-adjusted launch prices. Methods: We hand-collected data on 56 anticancer drugs newly approved between 1995 and 2013. We measured launch prices using Medicare reimbursement formulae for oral and IV drugs. Prices represent the cost of a course of therapy for the typical patient. We obtained information on survival benefits from phase III trials and modeling studies. We evaluated the relationship between drugs’ prices, survival benefits, and approval year. We adjusted prices for inflation using the Consumer Price Index. Results: We find that there have been economically and statistically significant increases in launch prices over time. The price of an additional month of survival time increased by $600 per year (95% CI: $100-$1,100; p = 0.02). Our model predicts that the launch price of a drug that extends median survival by 5 months would be $37,000 in 1995. If the same drug were launched in 2010, the price would have been $84,000. Results are robust to the inclusion of controls for side effect rates, administration route, and other drug attributes. Conclusions: Our results confirm what many suspect: newer anticancer drugs are more expensive than older agents. We explain pricing trends using “reference price” models of demand. Physicians are reluctant to prescribe drugs with prices they perceive as unreasonable. However, perceptions of reasonableness are malleable and influenced by the prices of previously-approved drugs, giving manufacturers leeway to increase launch prices over time.
A phase I/II study of sunitinib in young patients with advanced gastrointestinal stromal tumor.
Authors: Arnauld Verschuur, Jonathan C. Trent, Viera Bajciova, Aron D. Thall, Xun Lin, Reza Khosravan, Antonella Ingrosso, Katherine A. Janeway
Journal: Journal of Clinical Oncology (2014)

TPS10601 Background: Gastrointestinal stromal tumor (GIST) in young patients (pts) is a rare disease with distinct features from GIST in adults. Most notably, >85% of adults have tumors arising from receptor tyrosine kinase (RTK) mutations, typically in the KIT and PDGFRA genes, whereas such mutations occur in <15% of young GIST pts, for whom succinate dehydrogenase dysfunction is emerging as a central oncogenic mechanism instead. Sunitinib is an oral multitargeted RTK inhibitor approved for treatment of imatinib-resistant/intolerant GIST. With an IC50 of 245 nmol/L, sunitinib has a high in vitro activity against wild-type KIT compared with imatinib (IC50of 3,132 nmol/L). It is therefore hypothesized that sunitinib will be more active than imatinib in young GIST pts. This is supported by an expanded-access study, but with few pts and some limitations in data collection. A phase I study of sunitinib in pediatric pts with solid tumors, previously treated with multiple regimens of systemic chemotherapy, found that the MTD was half the effective dose in adult pts. It is not known if this will be reflective of the MTD in young GIST pts and/or if sunitinib will be effective at this dose. Methods: A single-arm, multinational, multicenter, phase I/II trial evaluating the pharmacokinetics, safety, and preliminary antitumor activity of sunitinib in ptsages 6 to <21 yrs with advanced, unresectable or recurrent GIST is open in North America, Europe, and Asia with 26 sites currently participating. Pts must have a histological diagnosis of GIST, measurable disease by RECIST, and imatinib-resistant/intolerant GIST or the non-mutant KIT genotype of GIST or not have access to imatinib in their country. Pediatric pts (<18 yrs) will receive sunitinib at a starting dose of 15 mg/m2/day on Schedule 4/2 (4 wks on treatment, 2 wks off) in repeated 6-wk cycles, with dose escalation permitted after cycle 1 based on tolerance and real-time pharmacokinetics; young adults will receive sunitinib 50 mg/day on Schedule 4/2. Thirty pts are planned, and 3 have been enrolled to date. This trial is currently enrolling. Contact Pfizer Oncology at 1-800-718-1021. Clinical trial information: NCT01396148.
Engineered Bcor Mutations Lead to Acute Lymphoblastic Leukemia of Progenitor B-1 Lymphocyte Origin in a Sensitized Background
Authors: Mianmian Yin, Yang Jo Chung, R. Coleman Lindsley, Yeulin Zhu, Robert L. Walker, Benjamin L. Ebert, Paul S. Meltzer, Peter D. Aplan
Journal: Blood (2018)
Malar Rash and Polyarthritis
Authors: Soumya Chatterjee
Journal: JAMA (2018)

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Functional comparison between genomic subtypes and protein signal transduction networks in metastatic triple-negative breast cancer tumor and stroma to identify actionable therapeutic strategies.
Authors: Virginia A. Espina, Joyce O'Shaughnessy, Maren K. Levin, John D. Carpten, David W. Craig, Daniel D. Von Hoff, Lance A. Liotta
Journal: Journal of Clinical Oncology (2014)

e22155 Background: Genomic sequencing has been conducted on primary TNBC, however it has been difficult to identify driver mutations that constitute actionable therapy strategies. Importantly, genomic profiling of primary TNBC may not correspond to the lethal metastatic mTNBC lesions. We conducted extensive proteomic signal pathway network analysis of microdissected tumor cells and stroma from mTNBC that have been subjected to full genomic sequencing. We addressed the following questions: 1) Can potential driver mutations in the metastasis be inferred from protein signaling pathways in the tumor cells? 2) Does the tumor cell signal pathway network reflect differences in local mTNBC versus the distant organ mTNBC? 3) Does the proteomic signaling profile of the stroma provide strategies for stromal therapy of mTNBC? We hypothesize that the functional comparison of the genomic subtype with the protein signal transduction pathways within the tumor-stromal microenvironment of the metastasis may provide novel therapeutic targets for TNBC. Methods: Whole genome and transcript sequencing was compared to 130 signal transduction proteins in the microdissected tumor and stroma of 13 mTNBC frozen samples, representing lymph node and local (n=7) and distant soft tissue (n=6) metastasis. Cell signaling pathway proteins were quantified by reverse phase protein microarray. Linkage analysis was done by non-parametric Spearman rho (rho>0.8, p<0.03) pair wise correlation. Results: Comparison of the tumor and stroma signaling network of local versus distant metastasis revealed that the stroma of distant metastasis were dominated by mTOR Ser2448/PTEN Ser380/HER4/SGK1 signaling (rho=0.9). Distant tumor signaling was dominated by STAT3 Ser727/Beclin1/AKT Thr308/COX2/TGFβ (rho=0.9). In contrast, stroma of local metastasis lacked the mTOR pathway linkages but exhibited HIF-1α-MET/Tyr1234/EGFR Ty1148 linkages (rho=0.9). Local tumor protein pathway linkages were similar to distant tumor signaling. Conclusions: Profiling mTNBC stromal signaling networks provides novel targets for new classes of stromal therapy.
CD38 Specific Chimeric Antigen Receptor KHYG-1 Natural Killer Cells: A Potential "Off the Shelf" Therapy for Multiple Myeloma
Authors: Arwen Stikvoort, Subhashis Sarkar, Renée Poels, Niels WCJ van de Donk, Sonja Zweegman, Michael E O'Dwyer, Tuna Mutis
Journal: Blood (2018)
Phase 2 Study of Lenalidomide Maintenance for Patients with High-Risk Acute Myeloid Leukemia in Remission
Authors: Iman Aboudalle, Hagop M. Kantarjian, Farhad Ravandi, Elias J. Jabbour, Naval G. Daver, Zeev E. Estrov, Michael Andreeff, Alessandra Ferrajoli, Courtney D. DiNardo, Naveen Pemmaraju, Kiran Naqvi, Nitin Jain, Sarah Gwen Pelletier, Guillermo Garcia-Manero, Jorge E. Cortes, Tapan M. Kadia
Journal: Blood (2018)
Busulfan with fludarabine myeloablative conditioning regimen in myeloid neoplasms: A single center experience.
Authors: Renju V. Raj, Anna M Button, Lindsay Dozeman, Margarida De Magalhaes-Silverman
Journal: Journal of Clinical Oncology (2014)

e18000 Background: The best conditioning regimen for patients undergoing myeloablative hematopoietic stem cell transplantation (HSCT) is unknown. Busulfan (Bu) and fludarabine (Flu) containing regimens have shown a good safety profile with low toxicity. A retrospective analysis of patients (pts) with myeloid neoplasms (AML/MDS/CML) who underwent allogeneic HSCT between 2008 and 2012 with myeloablative dose of busulfan and fludarabine is here reported. Methods: A total of 45 pts were included in the analysis. Twenty eight (62.2%) had AML, 15 (33.3%) MDS and 2 CML. The regimen consisted of IV Flu 40 mg/m2 and IV Bu 130 mg/m2 on days -6 to -3. Tacrolimus and methotrexate were used for graft-versus-host (GVHD) prophylaxis. Thymoglobulin (ATG) (4 mg/kg) was administered in unrelated and mismatched donor grafts. All received peripheral blood as source of stem cells. Fourteen donors were HLA identical related, 21matched unrelated and 10 mismatched unrelated. Median age was 58 (range 22-68) with 33 (73%) pts being older than 55. Disease risk by CIBMTR classification was early in 12 (27%) pts, intermediate in 6 (13%) and advanced in 27 (60%). HCT-CI scores were low in 3 (7%) pts, intermediate in 18(40%) pts and high in 24 (53%). Log Rank tests were used to analyze the overall survival. Results: All pts engrafted with a median time to neutrophil engraftment of 14 days (range 11-21). Grade II-IV and III-IV acute GVHD was diagnosed in 48% and 6.6% of pts. Chronic GVHD was diagnosed in 6 pts. Two pts (4%) died within 100 days of transplant. After a median follow up of 554 days (range 24-1987), 13 patients died with an actuarial overall survival (OS) of 71.1%. Six (46.2%) of the 13 pts had relapse or progressive disease. Other causes of death included: acute GVHD (1), infection (3), pulmonary toxicity (2) and sinusoidal obstruction syndrome (1). OS in patients with high HCT-CI was inferior compared to low and intermediate HCT-CI patients (p=0.0744). Conclusions: In our experience this regimen is well-tolerated and is associated with favorable outcome in this high risk patient population with myeloid neoplasms.