tbuckley/cabot-search huggingface dataset:
Survey of palliative care patients WHO work.
Authors: Paul A. Glare, Alberta Alickaj, Victoria Susana Blinder, Tanya Nikolova, Carey Ramirez, Vidya Raghavan, Janeen Crowley, Ethel Linda Frierson
Journal: Journal of Clinical Oncology (2013)

e20677 Background: There is an extensive literature on patients who return to work (RTW) after completing definitive cancer treatment. Much less is known about patients who work while on treatment. At a time of economic uncertainty as cancer becomes more of a chronic disease and palliative care is seen as offering much more than comfort care, issues affecting the working cancer patient needed to be explored. Methods: Cross sectional, anonymous survey completed once in two pain and palliative care clinics at a comprehensive cancer center by patients aged 25-65 who had been in paid employment prior to or during their treatment. Survey covered 37 items in three areas: cancer details (diagnosis, date of diagnosis, prior treatments, current disease status); occupation, work status and work ability; importance of work and factors interfering with work. Results: 97 surveys have been completed but up to 20% items missing responses. Cancer details: 54% females, median age 53, 79% working at diagnosis. Common primaries: Breast 26; CRC 14; lung 6; pancreas 4; prostate 2. 80% (67/84) reported having active disease, median 2 years since diagnosis, and 80% of them on treatment currently.Work status and attitudes of the 67 patients with active disease: 42% (29/68) are currently working, mostly full time, and typically will RTW after &lt; 6 months off. 39% would like to work more hours. Work is important to 73% them, making 78% "feel normal", and 53% that they are “beating the cancer”. Fatigue interfered with work in 49%, pain in 38%, and side effects of pain medicines in 31%. Almost ¼ were anxious or depressed about their work situation. More than 20% experienced discrimination in the work place, but usually minor. Conclusions: Many of these patients with advanced cancer were trying to remain in the work force, even when they are on treatment and are sick enough to need to be followed in a Pain &amp; Palliative Care clinic. Work is important to them and almost half would like to work more. Symptoms and side effects are interfering with their work ability. Some are experiencing discrimination in the work place. Interventions need to be developed to overcome some of these problems.
A phase II study of Recchia's immunomodulatory schedule (RIS) as a maintenance therapy in high-risk tumors after a response.
Authors: Manuel Sureda, Joseba Rebollo, Begona Vazquez, Pere Bretcha, Rosa Cañon, Maritza Duarte, Vicente Munoz, Antonio Brugarolas
Journal: Journal of Clinical Oncology (2013)

3074 Background: F. Recchia et al. (Interleukin-2 and 13-cis retinoic acid in the treatment of minimal residual disease: A phase II study. Int J Oncol. 20: 1275-1282, 2002) previously defined the possibility of achieving a chronic immune stimulation through a prolonged low dose sc interleukin 2 (IL2)-based schedule, leading to a prolongation of PFS in advanced cancer patients (pts). A confirmatory phase II study was started. Methods: Pts diagnosed of high risk solid tumors in response to chemotherapy were included. RIS consisted in low dose IL2 (1.8 MU sc per day, 5 days per week, 3 weeks per month) plus oral isotreonin (CRA, 0.5 mg/kg) the same days of IL2 and/or sc PEG-interferon (50 µg per week of treatment). No Chx was allowed with RIS, but concurrent maintenance with TKI or Hx was permitted. Results: Since 08/2007 to 01/2013, 69 pts (39 M/30 F, median age 60 y, range 31-78) were included. 51 pts were treated with stage IV disease. 36 pts entered in complete response (CR), 29 in partial response (PR), 1 with progressive disease, 3 adjuvant. 4/69 grade 3/4 toxicity, (6%): 1 fatal poliserositis resistant to cortisone after 20 months of RIS, 1 stopped RIS for reaction requiring steroids, 1 for multiinfarction dementia, 1 for grade 3 liver toxicity. 3 pts presented other alterations managed along the course of the RIS (1 PVT, 1 ITP, 1 angina resolved after stent placement). Grade 1-2 fever, fatigue and joint pain were commonly observed but usually controlled with NSAIDs. Among the 68 pts evaluable for response, one pt progressed, 26 presented stable disease (median TTP 3 mo, range 2-28), 3 presented PR (1 melanoma, 1 prostatic ca, 1 ovarian ca; 9, 11 and 28 mo respectively), and 38 maintained or presented CR (median TTP 19 mo, range 2-62+). Three pts in PR were converted to a CR during RIS (1 pancreatic ca, 1 ovarian ca, 1 larynx ca). Conclusions: In this study we confirm the previous results reported by F. Recchia et al. RIS represents a good alternative for high risk pts with solid tumors after systemic chemotherapy induced response with acceptable tolerability and offers in selected pts a possibility of obtaining a CR after a PR. Further validation and randomized studies are warranted.
Ir-192 pellet source HDR brachytherapy using wax surface mould applicators in head and neck cancer: A single institute experience.
Authors: Indibor singh Yengkhom
Journal: Journal of Clinical Oncology (2013)

e17029 Background: Surface mould brachytherapy is suitable for radiation treatment of superficial lesions in head and cancer and it is the choice of radiotherapy technique. Various isotopes viz, Radium, Cs-137, Ir-192 wire, co-60, Sr-90 has been used. Earlier customized acrylic mould with hollow needle or catheters were used. With the advent of Ir-192 HDR pellet source we used tissue equivalent thermo malleable wax surface moulds. Single plane was used but in lips, pinna and ala of nose double planar sandwich technique was used with good dosimitry and cosmetic effect. BED is calculated by using LQ model. Methods: A retrospective analysis of 20 cases superficial H &amp; N epithelial cancers treated with surface mould Brachytherapy using wax mould during 2008 to 2010 at RIMS is retrieved from the archive. HDR Ir-192 pellet source surface mould was used by positioning the flexible catheters in proper positions without distortion of geometry. The mould is made with wax plates by warming upto 70 degree Celsius in thermal water bath. The thickness of the slab is 1 cm and catheters embedded on surface and kept 1 to 1.5 cm gap and parallel to each other which can be bent or curved according to the surface contour. The fixation is reinforced with transpore /cellotapes. The dose delivered varies 500cgy 6 to 8 doses or daily 300 cgy for 5 to 7 fractions with BED calculated for LDR 2500cgy to 3000 cgy. Results: 20 cases were analysed: 8 Basal cell ca on face. SCC inner canthus 2, lips 2, pinna 1, ala nasi 2, alveolus 1, 1 hard palate, and 4 cheeks. One lip and one cheek has undergone resection with margin not free. All had disease less than 4 cm size and infiltration less than .5 cm. and clinically Node negative. At median follow up of 30 months 18 had no evidence of disease with good cosmesis and one patient with Ca. hard palate had local failure and one upper eyelid has recurrence after 9 months. Conclusions: The study though small in number indicates practicability and satisfactory results of using locally available tissue equivalent wax surface mould application therapy of HDR pellet source for very superficial T1 N0 lesions as primary mode or adjuvant radiotherapy in head and neck areas.
Androgen receptor (AR) level in the prostatectomy specimen predicts time to disease progression post androgen suppression therapy
Authors: C. Cordon-Cardo, M. J. Donovan, F. Khan, M. Teverovskiy, S. Hamann, S. Eggener, A. Vicars, P. Scardino
Journal: Journal of Clinical Oncology (2007)

5065 Background: The androgen receptor (AR) plays an important role in the initiation and growth of prostate cancer and its subsequent response to hormone therapy. Previous analyses, including our own, have determined that elevated AR protein in the prostatectomy specimen is associated with progression of disease. We hypothesized that AR levels may also be predictive of response to androgen deprivation therapy (ADT) by evaluating time to castrate rise in PSA in patients treated with ADT at the time of a biochemical recurrence. By utilizing quantitative immunofluorescence (IF) and spectral imaging we evaluated AR content as an independent predictor of therapeutic outcome. Methods: 63 of 881 patients treated by radical prostatectomy had received ADT for a biochemical rise in PSA and or clinical progression of their disease. 32 of 63 patients had progressed post-ADT with a castrate rise in PSA. Tissue microarrays with triplicate patient cores were stained with a multiplex immunofluorescent assay (IF) which contained the nuclear marker DAPI, along with the following antibodies: Androgen Receptor (AR), Racemase (AMACR), CK18, HMWK and p63. IF images were acquired with spectral un-mixing employed to develop antibody-cell-specific gray scale images. Utilizing image analysis algorithms, quantitative features including intensity and area for selected antigens was generated. Results: Eleven IF antigen features were evaluated after feature selection and filtering using the concordance index with respect to outcome. A total of 5 features were statistically significant for predicting time to progression post therapy of which 2 features (AR intensity within AMACR (+) and (-) epithelial cells; p=0.0003 and p=0.0021, respectively) demonstrated that elevated levels of AR were associated with a shortened time to castrate rise in PSA post ADT. Clinical features alone were not found to be statistically significant with respect to predicting outcome. Conclusions: AR levels in the prostatectomy sample appears to be a useful indicator for determining therapeutic ADT response and potentially guiding future treatment decision and patient monitoring. No significant financial relationships to disclose.
Paclitaxel, carboplatin, and etoposide (TCE) in advanced poorly differentiated neuroendocrine carcinoma.
Authors: Luisa Mantovani Loeffler, Elias Mauersberger, Arved Weimann, Dorit Kuerschner, Christoph Schimmelpfennig, Volker Wiechmann, Heike Bisanz, Gisela Zeissig, Samira Zeynalova, Hans-Joachim Schmoll
Journal: Journal of Clinical Oncology (2013)

e15096 Background: Only limited data are available on treatment outcomes in poorly differentiated neuroendocrine carcinomas. We evaluated retrospectively a complete series of consecutive patients with poorly differentiated neuroendocrine carcinoma treated with a regimen containing TCE in a single center. Methods: 50 new consecutively diagnosed patients were treated between 01/2000 and 04/2012 at St. Georg Hospital Cancer Center Leipzig. Dosing: paclitaxel (175-200mg/m² d1), carboplatin (AUC 6 d1) and etoposide (50/100mg d1-10) q3w (Hainsworth et al. JCO 2006, 22, 3548-3554). In cases of response after three cycles patients have been treated until progression or toxicities. Patient initial characteristics: age 61 years (range 23-85); 34 male, 16 female; 8/50 limited disease, 29/50 liver metastases, 13/50 only extra hepatic metastasis; 12/50 hormon active tumors. Histological confirmation, immunhistochemical staining (synaptophysin, chromogranin A) and proliferationsrate were performed in all cases. Resection of primary tumor was performed in 20/50 pts. Median no. of cycles was 4 (range 1-12 courses). CT-Scans of all patients were reviewed according to RECIST to detect maximal response. Results: 7/50 (14%) had CR, 20/50 PR (with a median reduction of the sum of diameters to 49%); 12/50 (24%) had no change; 7/50 PD (14%); 4/50 (8%) were not evaluable for response because of early death (3 sepsis, 1 liver failure). Median progression free survival time was 4.0 months (95% CI 2.9-5.1). The median overall survival time was 14,8 months (95% CI 9,5 -20,3). Major toxicity was myelosuppression. As a consequence paclitaxel dose was reduced to 175 mg/m² in the last 40 pts of this series (80%). Conclusions: TCE treatment is effective and induces tumor control in a substantial subgroup of patients. This analysis confirms the data of Hainsworth et al. and shows in an unselected population nearly the same encouraging results. [Table: see text]
Second surgical intervention and continuous adjuvant therapy with temozolomide improved survival time in patients with GBM
Authors: H. Urs Sebastian
Journal: Journal of Clinical Oncology (2007)

12536 Background: GBM is among the most debilitating malignant disease. A combination of surgery followed by concurrent radiochemotherapy (RCT) followed by adjuvant TMZ improves overall survival (OS) &amp; progression-free survival (PFS). This retrospective exploratory analysis evaluated the effect of different TMZ treatment regimens &amp; repeated surgical interventions on clinical outcome in patients with GBM. Methods: 28 pts with WHO Grade IV GBM diagnosed between 1998–2005 (age: 27–68 years) underwent maximum resection feasible, followed by RT (40–80Gy). 18 pts received standart adjuvant TMZ 150–200 mg/m 2 /d, d1–5/ 28d (TMZ-S) after initial surgery. 10 patients received no further treatment, until relapse. Results: 2/28 pts have not yet relapsed and continue to receive adjuvant TMZ-S (&gt;40 cycles, PFS 5.2 + yrs &amp; &gt;73 cycles; PFS 7.5+ yrs). In the 26 relapsed pts, PFS was 13.1 ± 13.0 mos (n=16, range: 2 - 48 ) in pts receiving TMZ-S compared to 9.5 ± 11.7 mos (n=10; range: 0.5 - 41) in pts with no adjuvant TMZ. At relapse, 12 had a second surgery with additional TMZ-S or TMZ 75 mg/m2/d, d1–14/21days (TMZ-LD) . 14 pts did not have a second surgery and were further treated with either TMZ-S or TMZ-LD. OS was 30.6 ± 13.7 mos in pts who received adjuvant TMZ-S followed by a change to TMZ-LD at relapse (n=5) compared to 18.3 ± 20.0 mos in pts who continued TMZ-S after relapse (n=6). Overall, the longest OS was observed in pts who received adjuvant TMZ-S with a second surgery followed by TMZ-LD at relapse (n= 2: PFS 57 &amp; 59 mo). The shortest OS was observed in pts who had neither adjuvant TMZ-S nor additional surgery (n=5; 3–15 mos). A single outlier in this group was a pt with an OS of 58 mos. Conclusion: Best outcome in our pts with relapsed GBM was observed in those who received initial resection/RT followed by adjuvant TMZ-S with subsequent re-resection and TMZ- LD at relapse. Pts unable to undergo re-resection appeared to still benefit from a change to TMZ-LD at relapse. No significant financial relationships to disclose.
Lung Perfusion Scintigraphy in Eisenmenger Syndrome Due to Patent Ductus Arteriosus
Authors: Kohei Mitsui, Reiko Woodhams, Ryutarou Ukisu, Yusuke Inoue
Journal: Clinical Nuclear Medicine (2019)

Eisenmenger syndrome refers to the elevation of pulmonary arterial pressure to the systemic level caused by an increased pulmonary vascular resistance with right-to-left shunt through an intracardiac or aortopulmonary communication. A 36-year-old woman with Eisenmenger syndrome due to patent ductus arteriosus underwent Tc-MAA lung perfusion scintigraphy to evaluate right-to-left shunt. Whole-body imaging visualized extrapulmonary activity in both kidneys, spleen, and intestinal tract, confirming the presence of right-to-left shunt. Accumulation in the brain was visible but much weaker compared with that in the body trunk and was limited to the left cerebral hemisphere, which reflected the location of the shunt pathway.
Biomarker analysis by breast cancer phenotype in African-American versus Caucasian patients: Correlates with survival
Authors: G. J. Morris, A. K. Topham, F. Guiles, P. McCue, G. F. Schwartz, P. K. Park, A. L. Rosenberg, K. Brill, H. Rui, E. P. Mitchell
Journal: Journal of Clinical Oncology (2007)

10551 Background: Breast carcinomas in African-American (AA) patients (pts) have poorer prognosis and higher likelihood of aggressive basal phenotype (triple negative for ER, PR, HER2) than those in Caucasian (C) patients (Carey et al, JAMA 2006, 295(21):2492; Morris et al, Breast Cancer Res Treat 2006, abstr 3055). We have additionally examined biomarker expression by phenotype in AA pts in our registry to further explain more aggressive behavior in this population. Methods: Stage, grade, ER, PR, Ki-67, HER2, and p53 expressions were compiled for breast carcinomas in 2,230 AA and C pts diagnosed between 1995–2004. Immunohistochemical markers were assayed using antibodies to the above proteins on paraffin-embedded formalin-fixed tissue. Differences in expression were analyzed by Chi- squared and Wilcoxon tests, and survival by Kaplan-Meier estimates. Results: AA pts have higher propensity for basal phenotype breast cancers (20.8% vs 10.4%, p&lt;0.001) and lower propensity for Luminal A/B (ER+/PR+-/HER2-) phenotype (44.2% vs. 54.1%, p&lt;0.001) as compared with C pts. Higher ki-67 proliferation index was found in AA pts (86.4% vs 78.8% in basal, p=0.3423; 37.1% vs. 26.7% in Luminal A/B p=0.0233) as compared with C pts. p53-positivity was higher in AA and C pts in all cases (p=0.0158), higher in AA pts with basal phenotype (p=0.2597), but identical in AA and C pts with luminal phenotypes (p=0.881). Survival was similar in basal phenotypes between races in all cases stage for stage, and controlled for ki-67 and p53 status, with a trend toward poorer survival among luminal phenotypes between races. Conclusions: AA pts have higher propensity for basal phenotype breast cancers than C pts, with higher ki-67 expression in both basal and luminal phenotypes, and higher p53 expression in basal phenotype, but these do not correlate with significant differences in survival by phenotype between races. As neither ki-67 index nor p53 expression can therefore solely explain differences in survival rates seen between races, molecular array studies between races and matched by phenotype are proposed. [Table: see text]
Characteristics of clinical trials for adolescent and young adult (AYA) cancer patients (pts) in Ontario.
Authors: Wilson Kwong, Graeme A Fraser, Ronald Barr, Dongsheng Tu, Ralph M. Meyer
Journal: Journal of Clinical Oncology (2013)

e17525 Background: Outcomes of pediatric and adult cancer pts have improved more than outcomes of AYA pts. Reduced access of AYA pts to clinical trials may partially account for this. Methods: The 10 cancers of highest annual incidence for pts ages 15-29 were identified using the 2005-09 SEER data base and searched on ClinicalTrials.gov (2012/OCT/27) using restriction terms “recruiting”, “intervention studies”, “Canada-Ontario”, and “Adult (18-65)”. Among trials identified, variables compared were sponsor (industry; not industry), intent (curative; palliative; other), endpoints (survival; disease control-adverse event; other), previous therapy (none; other), age (max &lt; 29; max&gt;29 but &lt;50; max&gt;50), intervention (drug; RT+/-drug; other) and randomized design (yes; no). Comparisons used a 2-tailed Fisher’s exact test. Results: We identified 139 trials, including (incidence rank order in bracket): breast-41 (8), non Hodgkin’s lymphoma-36 (4), CNS-30 (6) and acute lymphoblastic leukemia (ALL)-21[10]. There were 45 trials available for the other 6 indications; some trials permitted multiple indications. Most common features were non-industry sponsorship (58%), palliative intent (65%), disease control-adverse event primary endpoint (82%), not restricted to 1 st line therapy (76%), max age&gt;50 (69%), drug-only intervention (78%) and non-randomized design (56%). Among all trials, those with an age restriction did not significantly differ from trials with an age maximum of &gt;50. Industry sponsorship was associated with fewer non-drug-only trials (2% vs. 36%; p&lt;0.0001), curative trials (12% vs. 41%; p=0.0002) and age-restricted trials (10% vs. 48%; p&lt;0.0001). CNS and ALL trials were more likely to restrict age eligibility (60% vs. 13%; p&lt;0.0001 for CNS; 52% vs. 18%; p&lt;0.0001 for ALL) and have non-industry sponsorship (90% vs. 49%; p&lt;0.0001 for CNS; 76% vs. 24%; p=0.09 for ALL). Conclusions: Availability of clinical trials for Ontario AYA pts is very heterogeneous and no correlation is seen between AYA cancer-type incidence and number of trials. While CNS cancers and ALL appear unique, access and characteristics of trials for other AYA pts appear to relate to determinants associated with older patients.
The transcription factor TCF-1 enforces commitment to the innate lymphoid cell lineage
Authors: Christelle Harly, Devin Kenney, Gang Ren, Binbin Lai, Tobias Raabe, Qi Yang, Margaret C. Cam, Hai-Hui Xue, Keji Zhao, Avinash Bhandoola
Journal: Nature Immunology (2019)
ASP9521, a novel, selective, orally bioavailable AKR1C3 (type 5, 17ß-hydroxysteroid dehydrogenase) inhibitor: In vitro and in vivo characterization.
Authors: Aya Kikuchi, Kentaro Enjo, Takashi Furutani, Hidenori Azami, Tatsuya Nimi, Sadao Kuromitsu, Yoshiteru Kamiyma
Journal: Journal of Clinical Oncology (2013)

5046 Background: Aldo–keto reductase 1C3 (AKR1C3), also known as type 5, 17β-hydroxysteroid dehydrogenase, is reported to be highly expressed in human normal prostate and prostate cancer (PC) and the expression increases along with increasing malignancy or grade of PC. Since AKR1C3 converts the adrenal androgen, androstenedione (AD) into testosterone (T), combination with a GnRH analogue and AKR1C3 inhibitor would be expected to provide total androgen blockade in the treatment of castration-resistant prostate cancer (CRPC). We obtained a lead compound having a non-steroidal scaffold by high throughput screening (HTS) approaches for targeting enzyme activity of AKR1C3. After optimization of the lead compound, we found ASP9521 as a potent, selective, and orally bioavailable AKR1C3 inhibitor. Methods: The inhibitory effect of ASP9521 on enzymatic conversion from AD to T by AKR1C3 was evaluated in vitro, and in CWR22R xenograft models. Effect of PSA production and proliferation on LNCaP cells stably expressing AKR1C3 was examined. Pharmacokinetics in various animals were also investigated. Results: ASP9521 showed potent inhibitory effect on enzymatic conversion from AD to T by both human AKR1C3 and cynomolgus monkey homologues in a concentration-dependent manner, with IC50 values of 11 and 49 nmol/L, respectively ASP9521 suppressed both AD-dependent PSA production and cell proliferation in LNCaP cells exogenously expressing AKR1C3 in vitro. The bioavailability of ASP9521after oral administration of 1mg/kg were 30% and 78% in rat and dog, respectively. Furthermore, ASP9521 single oral administration of 3 mg/kg suppressed AD-induced intratumoral T production in CWR22R xenografted castrate nude mice, and this inhibitory effect was maintained for 24 h. In addition, ASP9521 was rapidly eliminated from plasma after oral administration while its intratumoral concentration remained high in tumors expressing AKR1C3. Conclusions: These preclinical in vitro and in vivo data are consistent with a potent inhibition of 17β-hydroxysteroid dehydrogenase. The results suggest that ASP9521 should be investigated further to elucidate its role as treatment for PC.