tbuckley/cabot-search huggingface dataset:
Physician age and surveillance intensity following curative-intent treatment for breast cancer patients.
Authors: Steven F. Abboud, Emad S. Allam, Julie A. Margenthaler, Ling Chen, Katherine S. Virgo, Frank E. Johnson
Journal: Journal of Clinical Oncology (2012)

6081 Background: Breast carcinoma is a large health care concern for patients, physicians, and society. 2.5 million women have been treated for breast cancer and are candidates for surveillance in the US. We have documented dramatic variation in post-treatment surveillance strategies utilized by ASCO experts caring for such patients. Since it is often asserted that younger physicians order more tests than older physicians, we sought to measure the effect of clinician age on post-treatment surveillance intensity for breast cancer patients by analyzing a recent survey of ASCO members. Methods: We surveyed the 3245 ASCO members who indicated that breast cancer treatment was a major focus of their practice. 4 succinct clinical vignettes describing generally healthy women with breast cancer of varying prognoses and a menu of 12 surveillance modalities were offered. The menu was chosen after a literature search indicated that no other surveillance tests were commonly used. We analyzed data from one of the 4 idealized vignettes only (the patient with TNM IIA carcinoma) and stratified responses by clinician age. Practice patterns were compared by years after completion of training (0-10, 11-20, 21-30, 30-40, &gt;40 years), a surrogate measure of physician age. Statistical analysis employed ANOVA. Results: There were 1012 responses; 915 were evaluable. Statistically significant differences were observed across age strata for CBC, liver function tests (LFTs), and serum CEA level only. For example, ASCO clinicians in practice for 0-10 years after completion of training recommended CBCs 1.3 + 1.4 (mean + SD) times in year 1. Those &gt; 40 years after completion of training recommended CBCs 2.4 + 1.3 times in year 1 (p&lt;0.001). Conclusions: Younger physicians recommend statistically significantly fewer CBCs, LFTs, and serum CEA levels during post-treatment surveillance than older physicians. However, the magnitude of the difference is clinically small for all 3 modalities and does not explain the known overall variation in surveillance practice among clinically active experts.
Physiologic Uterine Uptake of Radioiodine During Menstruation Demonstrated by SPECT/CT
Authors: Lina Liu, Yu Chen, Tian Tian, Rui Huang, Bin Liu
Journal: Clinical Nuclear Medicine (2019)

A 35-year-old woman with papillary thyroid cancer underwent I therapy after thyroidectomy. Post-therapy whole body scan revealed increased activity in the pelvis, in addition to the activity in the neck. On SPECT/CT images, the radioactivity in the pelvis was localized in the rectum and cervix. Further inquiry discovered that the patient was menstruating. We concluded that abnormal radioiodine uptake in menstrual uterus might be an exceptional finding mimicking a metastasis.
Stage, biology, and age.
Authors: Hee Jeong Kim, Beom Seok Ko, Jong Han Yu, jong Won Lee, Byung Ho Sohn, ku Sang Kim, Sung-Bae Kim, Sei-Hyun Ahn
Journal: Journal of Clinical Oncology (2013)

e11512 Background: Breast cancer subtypes are prognostic and predictive for patients. In this study, prognostic value of TNM stage, intrinsic subtype, and age were compared. Methods: We analyzed results from 7,626 breast cancer patients registered on the Asan medical center database between 1999 and 2009. We compared survival according to the TNM stage, intrinsic subtype using ER, PR, Her2- immunohistochemical staining, and age. Results: Luminal A subtype showed the best survival rates while triple negative subtype showed the worst survival rate amongst intrinsic subtypes. Survival analysis showed that Stage I triple negative breast cancer showed better survival compared to Stage III Luminal A subtype breast cancer (89.0% vs 76.6% P&lt;0.001). Survival differences between intrinsic subtypes were more significant in lymph node positive breast cancer compared to lymph node negative breast cancer. Age did not affect survival between stages and intrinsic subtypes except for the young age subgroup (≤35), for whom there was no survival difference amongst intrinsic subtypes. Conclusions: Staging of breast cancer showed a more direct correlation to survival than known prognosis for intrinsic subtypes, as advanced, good prognostic intrinsic subtype breast cancer had worse survival than early, worse prognostic intrinsic subtype breast cancer. However for the young age group (≤35), the survival of all intrinsic subtypes were similar.
A randomized, double-blind, phase (Ph) III study of the irinotecan-based chemotherapy FOLFIRI plus ramucirumab (RAM) or placebo (PL) in patients (pts) with metastatic colorectal carcinoma (mCRC) progressive during or following first-line therapy with bevacizumab (BEV), oxaliplatin (OXALI), and a fluoropyrimidine (FP) (RAISE) (NCT01183780).
Authors: Axel Grothey, Josep Tabernero, Philippe Rougier, Shaila Ballal, Heidi Crane, Mark D. Rutstein
Journal: Journal of Clinical Oncology (2012)

TPS3634 Background: Vascular endothelial growth factor (VEGF) and the VEGF receptor-2 (VEGFR-2) regulate angiogenesis and are overexpressed in CRC. RAM is a fully human IgG 1 monoclonal antibody that inhibits binding of VEGF ligands to VEGFR-2 and inhibits VEGFR-2 activation and signaling. In a preclinical study, antiangiogenic and antitumor effects were observed when DC101, an antibody that targets murine VEGFR-2, was administered to mice bearing human colon cancer xenografts. Antitumor activity for RAM has been demonstrated in a Ph I study in pts with solid tumors over a wide range of RAM dose levels and in a Ph II study with RAM + mFOLFOX-6 as 1st-line therapy in pts with mCRC. Methods: This ongoing, randomized, double-blind, placebo-controlled Ph III study includes mCRC pts with measurable or nonmeasurable disease and ECOG performance status of 0-1 who have experienced disease progression during or within 6 months following 1st-line therapy with BEV, OXALI, and any FP. Randomization is stratified by geographic region, KRAS status, and time to progression after initiation of 1st-line therapy. Pts are randomized 1:1 to either RAM 8 mg/kg or PL every 14 days. Pts in both arms receive FOLFIRI (irinotecan: 180 mg/m 2 , folinic acid: 400 mg/m 2 , 5-fluorouracil: 400 mg/m 2 bolus followed by 2400 mg/m 2 continuous infusion over 46-48 hours). The primary endpoint is overall survival (OS). The sample-size estimate assumes 85% power to detect at least a 2.5-month median OS difference (HR = 0.8) between treatment arms with a 1-sided alpha of 0.025. Secondary endpoints include progression-free survival, tumor response, safety, pharmacokinetics, immunogenicity, and correlations between biomarkers and clinical outcome. CRC tissue and blood collection is mandatory for biomarker analyses. As of 05 January 2012, 238 of 1050 planned pts have been enrolled from 100 sites in North America, South America, Europe, Asia, and Australia.
Racial and ethnic variation in employment and financial experiences of breast cancer survivors.
Authors: Reshma Jagsi, John A.E. Pottow, Kent A. Griffith, Ann S. Hamilton, John Graff, Steven J. Katz, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2013)

9601 Background: Concerns exist regarding the employment and financial experiences of cancer survivors and whether they differ by race/ethnicity. Methods: In a longitudinal survey of women reported to the Los Angeles and Detroit SEER registries for nonmetastatic breast cancer, we compared experiences of 4-year survivors by race/ethnicity. Results: Overall, 31% of 1,536 respondents (68% response rate) felt their financial status was worse since diagnosis (63% attributed this to breast cancer). This varied by race/ethnicity: 41% of Spanish-speaking Latinas (SSL), 33% English-speaking Latinas (ESL), 23% blacks (B), and 29% whites (W), p&lt;0.001. The median respondent had spent ≤$2000 on breast cancer medical expenses; 16% had spent &gt;$5000. 12% had medical debt 4 yrs post-diagnosis: 17% of ESL, 14% B, 10% SSL, and 9% W (p=0.01). Minority respondents were more likely to report foregoing medical care due to cost and other privations due to their medical expenses (Table). Overall, 14% felt their employment status was worse since diagnosis, and 61% of these attributed this to breast cancer. 755 worked for pay some time after diagnosis, of whom 56% said it was at least somewhat important to work to keep health insurance (55% of SSL, 65% ESL, 65% B, 50% W, p=0.03); 24% would look for a new job if assured of comparable benefits (45% of SSL, 29% ESL, 22% B, 17% W, p&lt;0.001); 7% had increased work hours to cover cancer-related expenses; 27% had decreased work hours due to cancer-related health issues; and 7% believed they had been denied job opportunities because of cancer. Conclusions: In this population-based sample of breast cancer survivors, job lock was common, and many women perceived being worse off with respect to finances and employment as a result of their breast cancer. Medical debt and privation varied significantly by race/ethnicity. [Table: see text]
Fibroblasts reduce tumor latency and increase tumor burden when coinjected subcutaneously with prostate carcinoma cells in a mouse xenograft model
Authors: Erik V. Verona, Junhua Yang, Abhik Bandyopadhyay, Luzhe Sun
Journal: Cancer Research (2005)

1025  A growing literature suggests a role of the stroma in carcinoma progression. It is believed that cytokines secreted from carcinoma cells stimulate stromal cells to secrete pro-growth factors which aid in the progression of the carcinoma. TGF-β is a candidate cytokine believed to participate in this communication. In prostate cancer, a reactive stroma has been described to support the formation of prostate intraepithelial neoplasia and eventually prostate carcinoma. Meanwhile, the number of fibroblasts decreases and the number of myofibroblasts increases in the reactive stroma. TGF-β is also known to directly mediate the differentiation of fibroblasts to myofibroblasts. In this study, we show that coinoculation of BJ human skin fibroblast cells with DU145 human prostate carcinoma cells subcutaneously into nude mice dramatically decreased tumor latency as well as increased tumor burden. Our study also showed that blocking TGF-β signaling in the fibroblast cells with ectopic expression of a dominant negative TGF-β type II receptor reduced their tumor promoting effect. We are currently investigating whether the abrogation of TGF-β signaling in the fibroblasts inhibited myofibroblast formation in the tumor stroma. Studies are also underway to determine whether similar results can be obtained when prostate-derived stromal cells with or without attenuated TGF-β signaling are orthotopically inoculated with prostate carcinoma cells. These studies should help us to gain a better understanding of the role of prostate stromal cells and stromal TGF-β signaling in prostate cancer progression.
Phase I/II trial of bendamustine, ixazomib, and dexamethasone in relapsed/refractory multiple myeloma
Authors: Binod Dhakal, Anita D’Souza, Mehdi Hamadani, Carlos Arce-Lara, Katrina Schroeder, Saurabh Chhabra, Nirav N. Shah, Katelyn Gauger, Taylor Keaton, Marcelo Pasquini, Parameswaran Hari
Journal: Blood Cancer Journal (2019)

Abstract In this phase I/II trial, BID, bendamustine (70, 80, or 90 mg/m 2 ), ixazomib (4 mg), and dexamethasone (40 mg), was administered to 28 patients with relapsed and/or refractory multiple myeloma (RRMM) exposed to bortezomib and lenalidomide and refractory to at least one. A 3 + 3 dose escalation based on dose-limiting toxicities (DLTs) was employed in phase I (total 15); 2/6 patients developed DLTs (neutropenia and thrombocytopenia) at dose level 3 establishing the recommended phase II dose as bendamustine 80 mg/m 2 , ixazomib 4 mg, and dexamethasone 40 mg. The median age was 67 years (range, 42–72), and 43% were females. Patients received a median of 4 (range, 4–9) prior lines of therapy, of which ~50% were double refractory. In phase II, total 19 patients were treated. With a median follow-up of 17 months, 11% achieved very good partial response, 50% achieved partial response, and 27% achieved stable disease. Median progression free (PFS) and overall (OS) survival were 5.2 months (95% CI, 1.96–8.3) and 23.2 months (95% CI 16.3–30.07). The most frequent adverse events were anemia, thrombocytopenia, leukopenia, nausea, diarrhea, and infections. Peripheral neuropathy was infrequent. BID is a well-tolerated and effective combination therapy for patients with RRMM.
Getting insights into hepatocellular carcinoma tumour heterogeneity by multiomics dissection
Authors: Pablo Sarobe, Fernando Corrales
Journal: Gut (2019)

Malignant tumours are composed of a heterogeneous collection of single cells with different molecular and phenotypic features, a phenomenon termed intratumoural heterogeneity (ITH) that is involved in tumour growth, progression, invasion and metastasis. This multilesion scenario represents a serious hurdle to accurate diagnoses and effective treatments that should be urgently circumvented to improve the clinical management of oncologic patients. To this end, many efforts have been devoted to investigate the morphological, environmental and molecular principles of ITH, specifically in hepatocellular carcinoma (HCC).1 Understanding tumour immunogenicity is a central topic in cancer therapy as immune microenvironment, human leucocyte antigen heterogeneity and tumour-specific neoantigens may lead to next-generation vaccination strategies.2 Genetic variation has been appointed as a source of ITH in HCC with pharmacological implication, although caution should be taken in the interpretation of mutational signatures3 that should be subjected to further validation. In this regard, orthogonal analyses combining complementary approaches to analyse different layers of biological information are currently providing a more precise phenotypic description to the molecular complexity resulting from ITH. The study of ITH by integrating different sources of information was already proposed in 1983 and in recent years the use of genome-wide exploration technologies is emerging as a resource with unprecedented capabilities …
Dual antiangiogenic therapy using lenalidomide and bevacizumab with docetaxel and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Bamidele Adesunloye, Xuan Huang, Yangmin M. Ning, Ravi A. Madan, James L. Gulley, Melony Beatson, Paul Gustav Kluetz, David E. Adelberg, Philip M. Arlen, Howard L. Parnes, Marcia Mulquin, Seth M. Steinberg, John Joseph Wright, Jane B. Trepel, Nancy Ann Dawson, Clara Chen, Carol Bassim, Andrea Borghese Apolo, William Douglas Figg, William L. Dahut
Journal: Journal of Clinical Oncology (2012)

4569 Background: Previously, we had shown the potent anti−tumor activity of dual anti-angiogenic therapy by combining bevacizumab (B) and thalidomide (T) with docetaxel (D) and prednisone (P) in mCRPC (Ning JCO 2010). We hypothesized that combining lenalidomide (L), an analogue of T, with B, D, and P would have a more favorable efficacy/toxicity profile. Methods: All patients (pts) had chemotherapy−naïve mCRPC. Among the first 52 pts, 3 received L 15 mg daily, 3 had 20 mg daily, and the rest had 25 mg daily for 14 days of every 21−day cycle (C). The protocol was recently amended to enroll 11 more pts at L 15 mg; 2 pts have now been enrolled in this expansion cohort. All pts received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and enoxaparin daily throughout each C. Pegfilgrastim was given on day 2. PSA each C with imaging after C2 and after every 3C. Dental exams with mandible CT scan at baseline, after C5, and every 6C. Results: 54 of 62 pts have been enrolled. Median age 65.5 (51−82), Gleason score 8 (5−10), on−study PSA 85.2 ng/ml (0.15−3520), and pre−study PSA doubling time 1.49 months (0.52−6.73). Median number of Cs was 16 (3−38). PFS was 22 months and probability of survival at 12 months was 90%. Forty-six (85.2%) and 42 (77.8%) pts had PSA declines of ≥50% and ≥75%, respectively. Of 30 pts with measurable disease there were 1 CR and 25 PR (86.7% overall RR). 17/54 pts were off study for radiographic disease progression and 8/54 for other reasons. Grade ≥2 toxicities included neutropenia (34/54), anemia (23/54), thrombocytopenia (7/54), hypertension (12/54), perianal fistula (3/54), rectal fissure (1/54), myocardial infarction (1/54), and osteonecrosis of the jaw (ONJ) (12/54, 22.0%). At the time of diagnosis of ONJ, 7/12pts were on bisphosphonates (BP), 2/12 had used BP previously, and 3/12 never used BP. The incidence of ONJ was comparable to 18.3% reported by Ning et al. A recent study of carboplatin plus weekly docetaxel reported an incidence of 29.3%. Conclusions: Dual anti-angiogenic therapy with, B and L, plus D and P was associated with high PSA (85.2%) and tumor (86.7%) responses in mCRPC, with manageable toxicities. The incidence of ONJ is comparable to other studies.
lncRNA polymorphisms in EPF
Authors: S.C. Lobo‐Alves, D.G. Augusto, W.C.S. Magalhães, E. Tarazona‐Santos, M.F. Lima‐Costa, M.L. Barreto, B.L. Horta, R.C. Almeida, M.L. Petzl‐Erler
Journal: British Journal of Dermatology (2019)

Pemphigus foliaceus (PF) is a disease that causes painful blisters in the skin. Due to genetic and environmental reasons, the person's own immune system produces antibodies that attack proteins present in the top layer of the skin (the epidermis). Although PF is rare worldwide, there are some geographic regions where many people develop this disease, known as the endemic form of PF (EPF). In Brazil, EPF is also known as fogo selvagem. This study aimed at finding out if single changes in the DNA (called SNPs – single nucleotide polymorphisms) located in genes called lncRNA genes predispose people to EPF. There are several different variants of SNPs. The frequencies of 2,080 SNPs were compared between 229 EPF patients and 6,681 people without pemphigus (the controls). A variant of the SNP called rs7144332 was significantly more frequent among EPF patients than people without EPF, and is therefore associated with increased risk. Results for another five SNPs suggested that they also influence the susceptibility to (risk of) EPF. Further study showed that five of these six SNPs could affect the amount of lncRNAs or proteins produced by nearby genes. Along with other findings, this study shows that genetic variants of lncRNAs might contribute to the development of pemphigus, highlighting their importance in autoimmune and possibly other complex diseases.
Rapidly Progressing Renal Cell Cancer of the Left Native Kidney in a Renal Transplant Recipient With Unusual Sites of Metastasis Demonstrated in Serial 18F-FDG PET/CT
Authors: Kasturi Rangan B K, Manish Ora, Ajay Singh Suraj, Ashutosh Parashar, Sanjay Gambhir
Journal: Clinical Nuclear Medicine (2019)

Abstract An end-stage renal disease patient underwent renal transplantation 18 years back and was on triple immunosuppression for acute rejection. She presented with left-sided abdominal lump and underwent ultrasound and noncontrast CT scan, which revealed an exophytic mass lesion in atrophic left kidney (16.2 × 13.1 × 14 cm). Baseline 18 F-FDG PET/CT revealed a large avid exophytic mass (SUVmax 23, 17 × 14 × 13) in atrophic left kidney, with multiple retroperitoneal lymphadenopathies and a suspicious lung nodule. She underwent left open radical nephrectomy. Follow-up PET/CT after 1 month revealed multiple soft tissue deposits in operative bed and other unusual metastatic sites.
Cabazitaxel (Cbz) versus topotecan in patients (pts) with small cell lung cancer (SCLC) that has progressed during or after first-line treatment with platinum-based chemotherapy: A randomized phase II study.
Authors: Tracey L. Evans, Joo-Hang Kim, Frances A. Shepherd, Konstantinos N. Syrigos, Katalin Udud, Viacheslav Chubenko, Dariusz Kowalski, James R. Rigas, Gregory Lo, Jaafar Bennouna, Mustapha Chadjaa, Martin Wolf
Journal: Journal of Clinical Oncology (2013)

TPS7609 Background: Approximately 12–15% of pts with lung cancer have SCLC. Although first-line platinum-based chemotherapy regimens may be effective, pts often experience rapid relapse and develop systemic metastases. Median survival after SCLC relapse varies from 13 to 35 weeks. As such, there is a substantial unmet need for more effective second-line treatments. Clinical studies suggest that taxanes are effective in relapsed SCLC, and Cbz, a next-generation taxane, has shown efficacy in the second-line treatment of taxane-resistant tumors (de Bono JS, et al. Lancet 2010;376: 1147–54; Pivot X, et al. Ann Oncol 2008;19:1547–52). Assessment of Cbz treatment for SCLC is therefore warranted. Methods: This is a multinational, open-label Phase II study (NCT01500720) in pts with confirmed, measurable, locally advanced or metastatic SCLC whose disease has progressed during/after first-line platinum-based chemotherapy. Pts aged ≥ 18 years with ECOG performance status ≤ 1 are eligible, but those with &gt; 1 prior chemotherapy regimen or prior topotecan or taxane use are excluded. Pts are randomized 1:1 to receive IV Cbz 25 mg/m 2 (Day 1 Q3W) or IV topotecan 1.5 mg/m 2 (Days 1–5 Q3W). Pts are divided into chemo-sensitive and chemo-refractory subgroups, while stratification is based on the presence of brain metastases (yes vs no) and by lactate dehydrogenase plasma concentration (≤ or &gt; upper limit). Pts will be treated until disease progression, unacceptable toxicity or withdrawal of consent. The primary objective is assessment of progression-free survival (PFS). Secondary objectives include assessment of other efficacy endpoints (proportion of pts free of disease progression at 12 weeks, tumor response and overall survival), safety and health-related quality of life. A centralized imaging review process is being used to independently review tumor measurements. Planned enrollment is 172 pts (to provide 80% power for PFS analysis). The first pt was enrolled in March 2012. By December 2012, 91 pts had been randomized in 38 sites. Clinical trial information: NCT01500720.