tbuckley/cabot-search huggingface dataset:
Comparison of breast cancer subtypes detected by mammography screening and tumors diagnosed with palpable masses.
Authors: Cesar Gomez Raposo, Ines Suarez-Garcia, Miriam Lopez-Gomez, Isabel Esteban, Monica Andreu, Jose Lorenzo Vazquez Osorio, Maria Sereno, Francisco Zambrana Tevar, Maria Merino, Mar Carballo, Clara Garcia de Santiago, Javier Heras, Eva Pelayo, Purificacion Dominguez Franjo, Julio Alvarez Bernardi, Enrique Casado
Journal: Journal of Clinical Oncology (2012)

e11028 Background: Recent studies have reported a greater mean breast density associated with estrogen receptor (ER)-positive disease than with ER-negative tumors, but controversial results have been published. The purpose of our study was to compare the difference in the distribution of breast cancer subtypes detected either by mammography screening or tumors diagnosed with clinically palpable masses in our centre. Methods: Between June 2008 and December 2011 157 patients with age between 40 and 70 years-old were diagnosed of early stage breast cancer. Tumors were classified in three major breast cancer subtypes by immunohistochemistry: TN (ie, ER, PR and Her2 negative), Her2-positive (ie, Her2 positive; ER and PR may be positive or negative), and ER-positive/Her2 negative (ie, ER positive, Her2 negative, PR may be positive or negative) types. Tumor characteristics and type of diagnosis (mammography screening or palpable masses) were obtained by retrospective chart review. Associations between categorical variables were evaluated with the X 2 test. Results: Seventy patients (44.6%) were diagnosed of breast cancer with screening mammography, whereas 85 (54.1%) cases were detected by clinical suspected masses. Distribution according to molecular subtype defined by IHC were as follows: 123 (78.3%) ER-positive/Her2-negative tumors, 15 (9.6%) TN tumors, and 19 (12.1%) Her2-positive tumors. Less Her2-positive and TN tumors were significantly diagnosed with mammography screening (p=0.039 and p=0,020, respectively). No statistical differences were showed between ER-positive/Her2-negative tumors diagnosed with mammography screening and clinical palpable masses (p=0.78). Conclusions: The results presented in our study suggest that biologically aggressive subtypes of breast cancer are less frequently diagnosed with mammography screening in comparison with ER-positive/Her-2 negative tumors. Nevertheless, given the limited number of patients included and the bias related to retrospective studies these results must be interpreted with caution.
Pattern of chemotherapy dosing in obese patients in a community hospital.
Authors: Malar Thwin, Aye Min Soe, Nay Min Tun, Gina M. Villani
Journal: Journal of Clinical Oncology (2012)

e13099 Background: Obesity has increased to epidemic proportions, with 32.2% of US adults aged 20 years or older classified as obese (body mass index ≥ 30 mg/m 2 ). In view of altered pharmacokinetics and possible excessive toxicity in obese patients, chemotherapy dose reductions are often employed in treating obese cancer patients. To our knowledge, there are no reports in the literature identifying patients who should have empiric dose adjustment because of obesity or the best method of dosing chemotherapy to standardize drug exposure in patients with varying degrees of obesity. As practice varies among institutions, we carried out a retrospective study to evaluate the chemotherapy dosing pattern in our obese patient population. Methods: Charts of patients who received chemotherapy at our institution during the year 2010 were reviewed. Data on age, height, weight, type and stage of cancer, date of chemotherapy, and type and dose of chemotherapy were retrieved from chart review. Only details of the first chemotherapy cycle at our institution were collected. Body surface area (BSA) was calculated by using the Mosteller formula. Independent samples t-test and Pearson chi-square statistics were used to investigate the difference between the means and proportions respectively. Results: Data from 191 patients were analyzed. Distributions (mean and range) of age, height, weight, body mass index (BMI) and BSA were 60 years (26 - 88), 65 inches (53 - 79), 166 pounds (90 - 340), 27.44 kg/m 2 (14.52 - 56.57) and 1.85 m 2 (1.36 - 2.66), respectively. Patients who had a full dose (n = 164) had a mean BMI of 27 kg/m 2 (standard deviation (SD) 6.5) and a mean BSA of 1.82 m 2 (SD 0.24) whereas those with a reduced dose had BMI (n = 27, mean 30.2, SD 7.1) and BSA (mean 1.97, SD 0.25). There is a significant difference between the means of the two groups (full dose and reduced dose) in terms of both BSA and BMI (p = 0.033 and p = 0.01, respectively). Significantly higher proportion of patients with BSA ≥ 2 received reduced dose compared to those with BSA &lt; 2 (14 out of 48 (20.3%) versus 13 out of 143 (9%), p = 0.001). Conclusions: Patients with BSA ≥ 2 were more likely to get empiric chemotherapy dose adjustment at our institution. Further studies on chemotherapy dosing in obese patients are warranted.
A phase III randomized double-blind study of prophylactic topical dapsone 5% versus moisturizer for cetuximab-induced papulopustular (acneiform) rash.
Authors: Mario E. Lacouture, Viswanath Reddy Belum, Danielle Kehn, Andrea Cercek, Nancy E. Kemeny
Journal: Journal of Clinical Oncology (2015)

TPS9638 Background: Epidermal growth factor receptor inhibitors (EGFRI) such as cetuximab, are associated with an acneiform rash that can affect up to 90% of treated patients, and can lead to interruptions and discontinuation of treatment by 76% and 32% of oncologists, respectively. Affected patients experience significant impairment in their quality of life (QoL) and psychosocial well-being. Prophylactic therapies include topical corticosteroids in combination with oral antibiotics, or the latter as single agents. No nonsteroidal topical agent has hitherto been investigated for the prevention of rash. Dapsone, a sulfone anti-microbial agent with known anti-inflammatory properties, is approved for the topical treatment of acne vulgaris. It suppresses neutrophil recruitment (interferes with migration and β-2 integrin-mediated adherence), inhibits release of prostaglandins and leukotrienes, IL-8 (from keratinocytes), and generation of toxic, oxygen-derived free radicals. While the exact pathogenesis of the acneiform rash to EGFRIs is not known, neutrophil recruitment and activation appear to play a key role. Therefore, we hypothesized that topical dapsone may be a safe and effective preventative strategy. Methods: We designed a prospective, randomized double-blind controlled trial to measure the ability of twice daily split-face and chest application of topical dapsone 5% gel versus moisturizer, to reduce the total lesion count (of the acneiform rash) by 20% at day 28, in conjunction with oral antibiotics. Up to 40 subjects (80 sides) with metastatic colorectal cancer or head and neck squamous cell carcinoma will be randomized and monitored for 6 weeks. Secondary objectives include evaluation of the difference in dermatologic QoL between the side of the face/ chest treated with dapsone versus the contralateral side treated with moisturizer, using the Skindex-16/FACT-EGFRI-18 questionnaires. The difference in global severity of rash between the two application sides will also be evaluated by measuring the agreement of blinded independent dermatologists’ review of day-28 standardized photography of both sides. ClinicalTrials.gov: NCT01931150. Clinical trial information: NCT01931150.
Total costs of therapy with lenalidomide or bortezomib in relapsed/refractory multiple myeloma (rrMM).
Authors: Ivan Borrello, Gary Binder, Zeba M. Khan, Chris L Pashos, Brian G. Durie
Journal: Journal of Clinical Oncology (2012)

e18561 Background: Advances in survival are increasing payers’ focus on the cost of care in rrMM. An economic assessment was conducted from the perspective of a US payer to compare the total costs of treatment with two NCCN guideline-listed therapies frequently used in rrMM: lenalidomide plus dexamethasone (LEN/DEX) and bortezomib (BORT). Methods: Costs of drug treatment, medical resource utilization, and adverse event (AE) management were determined for each regimen over a common 12-month time-period. Utilization rates and costs of specific medical procedures (e.g., lab tests, hydration, AE prophylaxis, and physician administration) as well as incidence and costs of grade 3/4 AEs, were calculated based on published literature, 3Q2011 fee schedules, and respective package inserts. Median time to progression (TTP) was obtained from the respective pivotal clinical trials (BORT, 6.2 months [APEX] and LEN/DEX, 13.4 months [MM-009/MM-010]). Univariate sensitivity analyses and alternative scenarios were conducted to confirm robustness. Relative cost per outcome (i.e., treatment cost per month during which disease control had been maintained) was also analyzed for the treatment regimens. Results: Although drug acquisition costs for the two regimens were similar (difference of &lt;$10/day), total rrMM treatment cost per day was $58 higher with BORT ($356/day) vs. LEN/DEX ($298/day) due to higher physician administration, lab tests, and other medical and AE management costs for BORT. Annual total cost for BORT treatment was more than $20,000 higher than for LEN/DEX. A cost advantage for LEN/DEX was maintained across a variety of sensitivity analyses and alternative scenarios, including alternate therapy after relapse, changes to patient cost-sharing, and shorter time periods. Total cost per month without progression was 14% lower for treatment with LEN/DEX vs BORT. Conclusions: In rrMM, LEN/DEX and BORT had comparable drug acquisition costs, yet BORT had higher total costs due to physician administration and other medical resource and AE costs. Total cost per outcome (defined as month without progression) was lower with LEN/DEX.
Phase I Escalating-Dose Trial of CAR-T Therapy Targeting CEA+ Metastatic Colorectal Cancers
Authors: Chengcheng Zhang, Zhe Wang, Zhi Yang, Meiling Wang, Shiqi Li, Yunyan Li, Rui Zhang, Zhouxing Xiong, Zhihao Wei, Junjie Shen, Yongli Luo, Qianzhen Zhang, Limei Liu, Hong Qin, Wei Liu, Feng Wu, Wei Chen, Feng Pan, Xianquan Zhang, Ping Bie, Houjie Liang, Gabriele Pecher, Cheng Qian
Journal: Molecular Therapy (2017)

Chimeric antigen receptor T (CAR-T) cells have shown promising efficacy in treatment of hematological malignancies, but its applications in solid tumors need further exploration. In this study, we investigated CAR-T therapy targeting carcino-embryonic antigen (CEA)-positive colorectal cancer (CRC) patients with metastases to evaluate its safety and efficacy. Five escalating dose levels (DLs) (1 × 105 to 1 × 108/CAR+/kg cells) of CAR-T were applied in 10 CRC patients. Our data showed that severe adverse events related to CAR-T therapy were not observed. Of the 10 patients, 7 patients who experienced progressive disease (PD) in previous treatments had stable disease after CAR-T therapy. Two patients remained with stable disease for more than 30 weeks, and two patients showed tumor shrinkage by positron emission tomography (PET)/computed tomography (CT) and MRI analysis, respectively. Decline of serum CEA level was apparent in most patients even in long-term observation. Furthermore, we observed persistence of CAR-T cells in peripheral blood of patients receiving high doses of CAR-T therapy. Importantly, we observed CAR-T cell proliferation especially in patients after a second CAR-T therapy. Taken together, we demonstrated that CEA CAR-T cell therapy was well tolerated in CEA+ CRC patients even in high doses, and some efficacy was observed in most of the treated patients.
Efficacy of capecitabine monotherapy as the first-line treatment of metastatic HER-2 negative breast cancer.
Authors: Kadri Altundag, Taner Babacan, Orhan Efe, Ahmet S. Hasırcı, Fatih Demirci, Hakan Buyukhatıpoglu, Ozan Balakan, Furkan Saim Sarıcı, Neyran Kertmen, Ece Esin, Serkan Akin, Ozturk Ates, Sercan Aksoy, Ali R Sever
Journal: Journal of Clinical Oncology (2015)

e12035 Background: Capecitabine is a potent and safe agent, which can be used after antracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of capecitabine monotherapy as a first-line treatment in HER-2 negative MBC patients. Methods: In this single center trial, a total of 109 HER-2 negative MBC patients who received capecitabine monotherapy in the first-line treatment between 2003 and 2014 were retrospectively analyzed.Kaplan Meier survival analysis was carried out for progression free survival (PFS) and for overall survival (OS). Two-sided p values of < 0.05 were considered as statistically significant. Results: Median PFS was 7.0 ±0.67 (CI: 5.6-8.3) months and median OS was 30 ±4.1 (CI: 21.8-38.1) months. First-line capecitabine treatment for HER-2 negative MBC was more effective in ER positive patient population compared to ER negative group (median PFS: 9 vs. 4 months (p = 0.002), median OS: 33 vs. 21 months (p = 0.01). Indeed, the overall response rate in ER negative group was 16%, while this was calculated as 38% for ER positive cases. While most of our patient population was treated with a higher dose (1250 mg/m2), the observed grade 3-4 toxicities were lower compared to some previously reported phase II and phase III capecitabine studies. Conclusions: Capecitabine monotherapy is an effective and safe regimen for ER positive, HER-2 negative MBC patients. Its low toxicity profile compared to other intravenous cytotoxic agents and the ease of its oral administration make this agent a preferable option for both physicians and patients.
Phase I dose escalation study of recombinant interleukin-21 (rIL-21, BMS-982470) in combination with ipilimumab (Ipi) in patients (pts) with advanced or metastatic melanoma (MM).
Authors: Shailender Bhatia, Brendan D. Curti, Michael S. Gordon, Jason Chesney, Theodore Logan, John A. Thompson, Nels Royer, Rachel Bittner, David Fontana, Joseph Grosso, Pamela L. Clemens, Lewis J. Cohen, Christoph Matthias Ahlers, Jon M. Wigginton, Patrick Hwu
Journal: Journal of Clinical Oncology (2013)

TPS3109 Background: Ipilimumab is a monoclonal anti-CTLA-4 antibody that promotes T-cell activation and has been approved for the treatment of pts with advanced melanoma. The cytokine rIL-21 is a T-cell and NK-cell growth factor that has also demonstrated antitumor activity in selected solid tumors including MM. We hypothesize that coordinated stimulation of T and/or NK cell function with rIL-21 in conjunction with T-cell checkpoint inhibitor blockade with Ipi will achieve enhanced biologic and clinical activity compared to either agent alone. Here we describe an ongoing phase Ib study to investigate the clinical and biologic effects of combined treatment with rIL-21 and Ipi in pts with MM. Methods: The phase I study includes dose escalation (Part 1) using a 6 + 6 design and cohort expansion (Part 2). In Part 1 (n=48), successive cohorts of pts with melanoma will be treated with rIL-21 in combination with Ipi as follows: Arm A, rIL-21 (10, 30, or 50 μg/kg daily x 5) + Ipi (3 or 10 mg/kg Q3W) in a 3 week cycle; or Arm B, rIL-21 (30, 100, or 150 μg/kg weekly) + Ipi (3 or 10 mg/kg Q3W) in a 3 week cycle. In Part 1, all subjects will receive an initial cycle with rIL-21 monotherapy (lead-in) for biomarker and PK assessment that will be the same as the dose of rIL-21 specified for the cohort. Four cycles of combination treatment will follow the lead-in with restaging evaluation after 4 combination cycles. Subjects with initial benefit are eligible for retreatment at progression. In Part 2, pts (n=25/arm) will be randomly assigned to one of 3 cohorts: Ipi monotherapy at 3 mg/kg Q3W or Ipi + weekly rIL-21 or Ipi + daily rIL-21 at the MTD determined for each schedule in Part 1. The primary objectives of this study are to evaluate the safety of rIL-21 + Ipi and to define the MTD of the respective rIL-21 + Ipi regimens. Secondary objectives include assessment of the preliminary antitumor activity, pharmacokinetics, and immunogenicity. Exploratory objectives include investigation of the immunologic effects of this combination in peripheral blood and paired tumor biopsy specimens, and the association of these effects with clinical outcome. Clinical trial information: NCT01489059.
The relationship among age, anxiety, and depression in older adults with cancer.
Authors: Talia Weiss, Christian J Nelson, William P. Tew, Molly Hardt, Supriya Gupta Mohile, Cynthia Owusu, Heidi D. Klepin, Cary P. Gross, Ajeet Gajra, Stuart M. Lichtman, Rupal Ramani, Vani Katheria, Laura Zavala, Arti Hurria
Journal: Journal of Clinical Oncology (2012)

9123 Background: Depression and anxiety are common psychological sequelae of cancer, resulting in decreased adherence to treatment regimens and longer hospital stays. In men with prostate cancer, aging is associated with reduced anxiety and increased depression. The overall goal of this study was to examine the association among age, anxiety, and depression in a cohort of older adults receiving chemotherapy (chemo). Methods: This is a secondary analysis of a prospective longitudinal study investigating chemotherapy toxicity in older adults with cancer. Eligibility included: age &gt; 65, diagnosis of cancer, and scheduled to receive a new chemo regimen. Baseline data (pre-chemotherapy) included: age, sociodemographics, tumor and treatment factors (including tumor type and stage), geriatric assessment parameters (functional status, comorbidities, psychological state, nutritional status, social support). Anxiety and depression were measured by the Hospital Anxiety and Depression Scale (HADS). Univariate and multiple regression analyses were conducted to test the relationship between age, anxiety, and depression. Results: The average age of the 500 patients (56% females) was 73.1 (range 65-91, SD+6.18) with 5% Stage I, 12% Stage II, 22% Stage III and 61% stage IV. Mean depression and anxiety scores were: 3.6+3.17; 4.7+3.60. Clinically significant depression was reported in 12.6% (n=62). Clinically significant anxiety was reported in 20.9% (n=103). In univariate analyses, there was no association between anxiety and age, or depression and age. In multivariable analyses, older age (beta= -0.07, p = 0.05) was associated with decreased anxiety, as well as lack of social support (p &lt; 0.01) and increased number of comorbidities (p &lt; 0.01). In multivariable analysis, depression was associated with lack of social support (p &lt; 0.01), increased number of comorbidities (p &lt; 0.01), and advanced stage (p &lt; 0.01). Conclusions: This study supports previous research that anxiety decreases with age in older adults with cancer. However, depression remained constant with increasing age. Greater resources and attention to identifying and treating the psychological sequelae of cancer in older adults are warranted.
Neuroendocrine tumor (NET) patient (pt) experience with disease management: Results from the first global NET pt surveyA collaboration between the International Neuroendocrine Cancer Alliance (INCA) and Novartis.
Authors: Simron Singh, Grace Goldstein, Maia Sissons, Teodora Kolarova, John Leyden
Journal: Journal of Clinical Oncology (2015)

e17737 Background: NETs are a rare heterogeneous group of malignancies commonly diagnosed at an advanced stage. The chronic nature and unpredictable disease course can result in a challenging journey for NET pts, as well as a lack of a common management pathway. Little is currently known about the patient experience in NETs. Methods: In 2014 (Feb-May), 1928 NET pts from > 12 countries (Americas, Asia, Europe, Oceania) participated in an anonymous online or paper survey on the NET pt experience conducted by Hall & Partners on behalf of INCA/Novartis and funded by Novartis. Comparisons significant at P< 0.05. Results: Most pts had gastrointestinal [GI] 54% or pancreatic 22% NETs. Pts reported seeing multiple (average 3) health care providers (HCPs) for NETs management. The majority of HCPs consulted were oncologists (70%), general practitioners (58%), and GI specialists (33%). While pts felt HCPs in general were very supportive (45%), they felt HCPs were only somewhat or not at all aware of NETs (69%) or poorly understood how NETs affected pts' lives (61%). Pts reported numerous investigations (mean 5.5/year), with increasing numbers over the past 5 years (≥5 years ago, 4.8; < 5 years ago, 5.9). Pts reported several fear-related emotions associated with NETs that diminished somewhat with ongoing management ( < 5 years vs ≥5 years since diagnosis): concerned (55% vs 48%); anxious/worried (50% vs 42%); uncertain (45% vs 40%); scared (28% vs 20%). While most pts did not feel very knowledgeable about NETs (54%), they reported being very knowledgeable about NET treatment options (71%). Most (57%) rated currently available treatments as good/very good. However, many reported not having access to treatments, including surgery (24%), chemotherapy (62%), and other drug therapy (44%). 83% of pts believed more treatment options are needed. Pts with longstanding NETs ( > 5 years) were more likely to travel abroad for NETs treatment (5% vs 11%). Conclusions: This large international survey is the first studied pt perspective on NETs. Pts reported large unmet needs with regard to NETs requiring further examination.
Retrospective review of patients with aggressive lymphomas treated with hyper-CVAD regimen –our institutional experience
Authors: V. Donthireddy, G. Kamboj, N. Janakiraman
Journal: Journal of Clinical Oncology (2004)

6736 Purpose: To evaluate the response and outcome of aggressive lymphomas treated with Hyper-CVAD/ MTX-Ara-C chemotherapy regimen at our institution and compare it with the historical control group. Methods: Patients with aggressive lymphomas were identified through the tumor registry from 1998 to 2003. 13 patients who received at least two courses of Hyper-CVAD chemotherapy regimen were identified. Rituximab was included in the regimen of 4 of the 13 patients. 6 patients had a diagnosis of Mantle Cell Lymphoma and 7 patients had a diagnosis of Acute Lymphoblastic Leukemia/transformed CLL. Median Age of the cohort was 57 (26- 82) with 8 male and 5 female patients. Results: Hyper CVAD / MTX-Ara–C treatment induced an overall response rate of 62% (46%CR; 23%PR). There were no direct treatment related deaths. The overall survival was 18.3 months. Toxicities included grade-4 neutropenia (100%), grade-4 thrombocytopenia (100%). 10 of the 13 patients had at-least 1 episode of febrile neutropenia (15 episodes in 78 cycles). Other toxicities included grade-2 neuropathy (1), disseminated herpes (1), delayed marrow recovery (3), perirectal abscess (1), ICU transfers (2). Subsequently 6 patients went on to receive bone marrow transplantation. Only 4 of the 13 patients who received Hyper CVAD were alive at the time of reporting of this data. Discussion: The published data seems to be superior to what the experience has been at our institution. In this small group of patients we found that this regimen is extremely difficult to deliver with lower response rates (62% vs. 81–100%) and higher toxicities as compared to the published data. Alternate more effective and less toxic regimens need to be developed for these aggressive lymphomas. No significant financial relationships to disclose.