tbuckley/cabot-search huggingface dataset:
High dose celecoxib (C) and docetaxel (D) in patients (pts) with hormone resistant prostate cancer (HRPC). Results of an ongoing phase II trial
Authors: B. Kasimis, J. Cogswell, S. Hwang, V. T. Chang, S. Srinivas, F. Zhong, L. Duque, E. Morales, I. Boholli, M. Blumenfrucht
Journal: Journal of Clinical Oncology (2005)

4704 Background: Cox-2 expression has angiogenic and cytoprotective effects and its suppression could increase the response to chemotherapy. Cox-2 is overexpressed in 89.3% of pts with prostate cancer and it is an independent predictor of survival (Proc ASCO 2003,abst #1675). D and C exhibit antiangiogeneic activity and induce apoptosis. A combination of D and C could be synergistic. The objectives were to determine their effects on PSA, overall response (OR), toxicity, time to progression (TTP) and survival. Methods: Twenty eight (28) pts with HRPC progressing by rising PSA and scans were treated with D 30mg/m2 IV/wk over 30min for 3 wks and C 400mg po bid for 4 wk cycle. All were assessed by PSA and scans every 2 cycles. Dose modifications for hematology and renal toxicities were made. The RECIST criteria, PSA decline by ≥50% and the Simon’s Optimal Two-Stage design were used. Results: To date 28 pts have enrolled. Twenty seven (27) pts have received a minimum of 2 cycles, median (M) was 3 cycles (range 2–6) of D and C. One (1) pt received one cycle. The M age was 73 years (55–94), ECOG PS 1(0–1), LDH 186.5 U/L (125–899), Hgb 12.1 g/dL (8.6–14.6), PSA 93.6 ng/dL (15.3–4192). 81.5% of pts had soft tissue and 85.2% had bone metastases. Twenty seven (27) pts are evaluable for response. Of those, 11 pts (41%) had PSA response with normalization in 3 (11.1%); 6 pts (33.3%) had soft tissue response with 3 CR, 3 PR and 14 pts (51.9%) had stable disease. One (1) pt had major improvement on bone scan. OR was documented in 13 pts (48.2%). M TTP by PSA was 3.7 months (0.7 -10.8+) and by scans was 7.7 months (1.4 -14.9+). The M survival has not been reached after 12.5 months of follow up (3.0–17.8+). One pt withdrew due to abdominal discomfort, 2 pts (11.7%) had grade III diarrhea and 1 pt had grade III nail changes. There was excellent renal and cardiovascular tolerance. Conclusions: The combination of D and C is well tolerated. The OR rate was 48.2% with PSA normalization, soft tissue response and bone scan improvement. Longer follow up will determine the full impact of this active combination. Sponsored by Aventis Sanofi and Pfizer Pharmaceuticals. No significant financial relationships to disclose.
The association of obesity, smoking, and access to oncology services with cancer mortality in the United States.
Authors: A. J. Hayanga, S. B. Zeliadt, D. E. Wood, L. M. Backhus
Journal: Journal of Clinical Oncology (2011)

6023 Background: Access to care and modifiable risk factors such as obesity and smoking vary greatly by geographic region. We examined the influence of these factors on cancer mortality rates for lung, breast and colon cancers in the United States (US). Methods: Age-standardized cancer mortality rates for each county in the US per the National Center for Health Statistics were combined with county level hospital and provider density rates from the 2009 Area Resource File (ARF) together with data from the County Health Rankings project from the Wisconsin Population Health Institute and Robert Wood Johnson Foundation. Separate multivariate generalized linear models with Poisson distribution and log link were fitted for each cancer type. We examined the relationship between access, modifiable risk factors and cancer mortality rates, adjusting for county income level, population density, and urbanicity. We excluded small counties where mortality rates were unavailable or risk factor data missing. All analyses were weighted to reflect the population of each county. Results: A total of 2259 counties were included, representing 96.4% of the US population. The density of primary care providers and hospitals with oncology services varied widely across the U.S. There was no influence of provider density or oncology services availability on mortality rates for any of the leading cancers. There was less variability in the distribution of adult smokers and obesity across US counties; however, both factors were strongly associated with higher mortality rates for all cancers. In counties with < 16% adult smokers, for example, the adjusted lung cancer mortality rate was 43.7 per 100,000, while in counties with >22% adults smokers the rate was 61.6 per 100,000 (p<.001). Conclusions: Obesity and smoking were strongly associated with higher cancer mortality rates for most cancers, while access to primary and specialty oncologic services had no association with lower mortality rates. Health service initiatives geared at tackling modifiable risk factors such as adult obesity and smoking may have an important impact on reducing overall cancer mortality.
Colon cancer in immigrants from Ethiopia.
Authors: Nirit Yarom, Elena Gorbatsevich, Nir Geva, Ella Evron, Svetlana Kovel, Arnold Cyjon, Avishay Sella
Journal: Journal of Clinical Oncology (2015)

521 Background: During the period 1980-1990, 26,000 African Jews immigrated from Ethiopia to Israel. Reports of the prevalence of cancer in Ethiopia are scarce and difficult to verify. Kaposi sarcoma, liver, prostate, cervical and breast cancer as reported to be the most common cancers. Colon cancer entails less than 7% of all cancers. The aim of this study was to describe and characterize cancer in immigrants from Ethiopia in Israel, in order to tailor screening and treatment approaches to this unique population. Methods: In this retrospective single center study, patients were identified based on the country of birth as registered in the medical records. Clinical data including age at diagnosis, pathology, tumor stage, interval from onset of symptoms to diagnosis and to treatment, response to treatment and survival, were obtained from the clinical charts. Local REB approved the study. Results: Between the years 2003 and 2011, 53 immigrants were treated for cancer in our center. Median survival was 30 months. Patients diagnosed more than 22 years after immigrating to Israel had a better survival (median 79 m) than patients who were diagnosed earlier (median 16 m). The interval from onset of symptoms to diagnosis was found to correlate negatively with stage at diagnosis (R 2 =0.717). Out of 53 patients 10 had colon cancer (19%). Three patients were diagnosed at stage I or II and 7 at stages III or IV. Median age at diagnosis of patients with colon cancer was 56 (31-81). Median interval from immigration to diagnosis was 22 years (16-31). Median survival (all stages) was 12.5 m and the mean was 33.2 m. Seven patients had well to moderately differentiated adenocarcinoma, two had mixed adeno-neuroendocrine carcinoma and one patient had neuroendocrine tumor. Three out of four patients who were diagnosed with locally advanced, stage IIb-III, refused adjuvant chemotherapy. All those with recurrence consented to palliative treatment. None of the patients offered genetic consultation opted for consultation. Conclusions: Jewish immigrants from Ethiopia to Israel have a high prevalence of colon cancer at younger age and complicated pathology. Further molecular testing and epidemiologic studies should be pursued in order to understand the unique properties of cancers arising in this population.
Urinary function after image-guided intensity modulated radiation therapy (IG-IMRT) of localized prostate cancer.
Authors: Edward Obedian, Shawn H. Zimberg, Deepak A. Kapoor, Carl A. Olsson
Journal: Journal of Clinical Oncology (2014)

141 Background: Men choosing treatment for prostate cancer risk potential urinary dysfunction or incontinence. The purpose of this study was to determine the effect of high dose image-guided intensity modulated radiation therapy (IG-IMRT) on urine control and function in such men. Methods: Between March 31, 2008 and September 28, 2012, 3,602 men received high dose IG-IMRT for localized prostate cancer with sufficient data for review, including baseline and minimum 11 month follow-up evaluation of urine control and function. The latter were determined by a urinary continence grading questionnaire and the International Prostate Symptom Score (IPSS). These questionnaires were completed by all men prior to radiation (baseline) and at every follow up visit. The continence questionnaire separated patients as G0: no incontinence, G1: minimal incontinence not requiring pads, G2: incontinence requiring pads, and G3: incontinence interfering with daily life activities. Men with IPSS scores of 0 to 7 were deemed mildly, 8 to 19 moderately, and 20 to 35 severely symptomatic. Typical therapy was 8100 cGy delivered to the prostate in 45 fractions. Pelvic lymph nodes were treated in 13% (458) of the cases. Results: At baseline, incontinence grading in our 3,602 men was G0 in 3,086 (86%), G1 in 479 (13%) and G2/3 in 37 (1%) and IPSS was 0-7 in 2092 (58%), 8 to 19 in 1,276 (35%) and 20 or more in 233 (6.5%). After IG-IMRT, 2,635 (85%) of baseline GO men remained continent, 408 (13%) developed G1 incontinence and 43 (1.1%) developed G2/3 incontinence. Of 479 baseline G1 incontinent men, 259 (54%) improved to G0. Of 37 baseline G2/G3 incontinent men, 21 (57%) improved to G0/1 incontinence. In 2,092 mildly symptomatic men by IPSS (average 3.5 at baseline), there was a rise to 5.4 but 1,619 (77%) remained mildly symptomatic. In the 1,276 moderately symptomatic men at baseline the average IPSS (12) decreased to 9.8 at last follow up (p&lt;0.001). Similarly, in the 233 severely symptomatic men at baseline the average IPSS (24) dropped to 13 at last follow up (p&lt;0.001). Conclusions: Urinary incontinence following high dose IG-IMRT for prostate cancer is rare. IG-IMRT seems to improve some men with baseline urinary incontinence and higher IPSS scores. High dose IG-IMRT remains a good treatment option for localized prostate cancer.
Transarterial chemoembolization (TACE) does have little impact on hepatic metabolic function in patients with hepatocelluar carcinoma (HCC).
Authors: K. Schuette, J. Bornschein, O. Milbradt, K. Mohnike, P. Stuebs, P. Malfertheiner
Journal: Journal of Clinical Oncology (2011)

e14527 Background: 70-90% of patients with HCC suffer from liver cirrhosis. A high proportion present with impaired liver function which is critical for the selection of treatment. Locoregional therapeutic measures such as transarterial chemoembolisation (TACE) lead to further deterioration of liver function, but so far the effect of TACE on hepatic mitochondrial metabolic function is not adequately studied. We used the 13C-aminopyrine breath test, a validated tool, for the assessment of mitochondrial liver function. Methods: 11 patients (10 male, 1 female, median age 68.9 years, range 38-83 years) underwent a total of 16 TACE sessions. 10 of these patients suffered from liver cirrhosis. 8 were in Child A, 2 in Child B stage. For the assessment of hepatic metabolic function 13C-aminopyrine breath test was performed the day before TACE (n = 16), the day after TACE (n = 16) and 30 day post intervention (n = 12). The percentage of cumulative dose of 13CO2 exhaled at 3 hours was assessed. A cumulative dose exceeding 12% is considered to be consistent with normal hepatic mitochondrial metabolic function. A paired two-sided T-Test was used to statistically compare the results with pre-interventional liver function. Results: All 11 patients showed impaired hepatic mitochondrial metabolic function before TACE was performed. TACE led to a slight decrease in hepatic mitochondrial function that fully restored 30 days after the intervention (Table). Conclusions: Larger studies are needed to prospectively analyze the influence of locoregional therapy in patients with HCC on liver function. Probably highly selective TACE may be conducted also in patients with HCC and more advanced stages of liver cirrhosis as it does have little impact on hepatic metabolic function. Pre-intervention Day 1 post TACE Day 30 post TACE Median percentage of cumulative dose 13CO2 (SD) exhaled 1.9% (2.96%) 0.65% (2.47%) p = 0.46 1.95% (SD 2.73%) p = 0.36
Impact of a novel decision counseling program on treatment knowledge, decisional conflict, and choice in men with early-stage, low-risk prostate cancer.
Authors: Jean H. Hoffman-Censits, Anett Petrich, Anna Quinn, Amy Leader, Leonard G. Gomella, Adam Dicker, Robert Benjamin Den, Mark Hurwitz, William Kevin Kelly, Costas D. Lallas, Katherine Burns, Edouard John Trabulsi, Ronald Myers
Journal: Journal of Clinical Oncology (2013)

9 Background: Active surveillance (AS - serial follow-up PSA, exam, and biopsy) is an option for men with early stage, low risk prostate cancer (LRPca). While data show comparable survival for AS vs active treatment (AT - surgery or radiation), currently most men with LRPca undergo AT. A pilot Decision Counseling Program (DCP) to assist men in making an informed, shared LRPca treatment decision was implemented. Methods: Men with LRPca seen at the Jefferson Genitourinary Multidisciplinary Cancer Center (JGUMDCC) were consented. A nurse educator (NE) reviewed risks/benefits of AS and AT; had the participant identify factors influencing treatment decision making and specify decision factor weights; entered data into an online DCP; and generated a report of participant treatment preference and decision factors. The report was used by the participant and clinicians in shared treatment decision making. A follow-up survey was administered 30 days after the visit, with treatment status assessed. Change in treatment-related knowledge and decisional conflict were measured using baseline and 30-day survey data. Results: Baseline decision counseling preference of 16 participants: 4 - AS, 8 equal for AS and AT, 4 - AT. At 30 days, 12 participants initiated AS, 4 chose AT; participant mean treatment knowledge scores (8-point scale) increased (+1.13 points); decisional conflict subscale scores (strongly disagree = 1, strongly agree = 5) decreased (uncertain: -1.15, uninformed: -1.36, unclear: -1.12; and unsupported: -1.15). Conclusions: Decision counseling and shared decision making helped participants become better informed about treatment choices and reduced uncertainty in treatment decision making. The combined intervention resulted in most participants choosing AS. Ongoing study recruitment, data collection, and analyses are planned.
Circulating tumor cells as predictive marker in panitumumab after progression of cetuximab in Japanese patients with KRAS wild-type metastatic colorectal cancer.
Authors: Yoshihito Ohhara, Satoshi Matsusaka, Eiji Shinozaki, Mitsukuni Suenaga, Nobuyuki Mizunuma, Kiyohiko Hatake, Toshiharu Yamaguchi
Journal: Journal of Clinical Oncology (2013)

440 Background: Panitumumab has a high affinity for epidermal growth factor receptor. Its utility as a salvage therapy is unknown in cetuximab-resistant colorectal cancer. We assessed the prognostic and predictive role of circulating tumor cells (CTC) in KRAS wild-type metastatic colorectal cancer (mCRC) patients treated with panitumumab after progression of cetuximab. Methods: Panitumumab (6 mg/kg, every 2 weeks) was administered as a salvage therapy to cetuximab-resistant mCRC. CTCs of whole blood at baseline were isolated and enumerated using immunomagnetics. Results: Nineteen patients were enrolled in this prospective study between July 2010 and March 2011. Five patients had stable disease (SD) with a response rate of 0%. Four patients reached long SD, which was defined as continuous SD of more than 120 days. All of the four patients had &lt;2 CTC. &lt;2 CTC showed an independent predictive role for progression-free survival (PFS) at multivariate analysis (HR; 7.275, p=0.013). Patients with &gt;2 CTC had shorter median PFS than those with &lt;2 CTC (1.8 and 3.6 months, p=0.008). There was no statistical significance in median OS between patients with &lt;2 CTC and those with &gt;2 CTC (3.2 and 6.7 months, p=0.164). Conclusions: Panitumumab may be effective for patients with &lt;2 CTC, KRAS-wild-type mCRC after progression of cetuximab.
Changes in T cell immunity in patients with metastatic castration resistant prostate treated with Radium-223 treatment.
Authors: Joseph W. Kim, Youna Kang, Min Shin, Hari Anant Deshpande, Michael E. Hurwitz, John D. Roberts, Joseph G. Cardinale, Ashwatha Narayana, Insoo Kang, Daniel Peter Petrylak
Journal: Journal of Clinical Oncology (2016)

295 Background: The bone seeking calcium mimetic, Radium223 (Ra223), emits high energy alpha particle that cause irreparable double strand DNA breaks in osseous metastases. Ra223 improves survival in patients with bone-predominant metastatic castration resistant prostate cancer (mCRPC). The effect of Ra223 on the host immune system, and T cell immunity in particular, is unknown. Methods: Eligible patients include men with mCRPC, osseous metastases and a clinical indication for Ra223 were eligible. Blood samples were collected at the following time points: prior to the first, second, and fourth treatments (tx) and 4 weeks after the sixth dose. Peripheral blood mononuclear cells (PBMCs) were purified and stained with a cocktail of antibodies to surface and effector immune molecules. Some PBMCs were stimulated and stained for intracellular cytokines (IFN-g, TNF-a, IL-13, IL-17, and IL-21). Stained cells were analyzed by flow cytometry. Results: A total seven patients completed at least two sample collections. The median number of prior lines of therapy was three. Median age was 71 (55-79). Median PSA was 78 (2-351). Effector memory (EM) CD8+ T cells were divided into two subsets expressing high and low levels of the IL-7 receptor alpha chain (IL-7Ra) with distinct cellular characteristics including perforin expression. The frequency of IL-7Ra high and low EM CD8+ T cells expressing programmed death protein 1 (PD-1) was decreased after Ra223 treatment (pre vs. post, median (%) ± interquartile range, 14.3 ± 12.9 vs. 7.2 ± 20.9, P = 0.03; 16.7 ± 28.8 vs. 14.1 ± 37.8, P = 0.015 by Wilcoxon matched-pairs signed rank test). A similar finding was observed in the frequency of memory CD4+ T cells expressing PD-1 after the treatment (median (%) ± interquartile range, 7.2 ± 7.7 vs. 3.9 ± 3.4, P= 0.03). Conclusions: In this preliminary cohort of patients, Ra223 tx was associated with decrease in PD-1 expression by effector T cells. Further investigations of an immune mechanism of Ra223 mediated antitumor activity are warranted.
Prognostic value of immunophenotyping profile in patients with diffuse large B-cell lymphoma
Authors: A. L. Basquiera, V. M. Grupe, C. E. Di Tada, A. d. Diller, E. D. Palazzo, J. J. García
Journal: Journal of Clinical Oncology (2005)

6736 Background: The genetic expression profile of diffuse large B-cell lymphoma (DLBCL) has allowed to characterize two main groups of DLBCL according to the germinal center (GC) or post-GC (activated B-cell) origin. The clinical impact of this differentiation by immunohistochemical analysis remains controversial. Objective: To analyze the prognostic value of clinical features and the immunophenotypical differentiation of DLBCL into GC and post-GC groups. Methods: Information was collected from patients with DLBCL from a single institution. In all cases, biopsy specimens were immunostained with CD10, bcl-6, MUM1, CD20, Ki 67, CD3 and CD5. GC lymphomas were CD10(+); CD10(+)/bcl-6(+)/MUM1(-); or CD10(-)/bcl-6(+)/MUM1(-). Post-GC lymphomas were CD10(-)/bcl-6(+)/MUM1(+); or CD10(-)/bcl-6(-)/MUM1(+). Results: We studied 27 cases, 13 males and 14 females (median age 53 years). Primary extranodal origin was identified in 9 cases (33%). At diagnosis, 15 patients (55%) had an International Prognostic Index (IPI) of 0–2 and 12 patients (45%) had an IPI score of 3–5. Distribution according to single-antigen expression was: CD10, 22%; bcl-6, 81%; MUM1, 59%. Considering the immunophenotyping profile, 13 cases (48%) were GC and 14 cases (52%) post-GC. After a median follow-up of 405 days (range, 118 - 1,474) 9 patients died. Progression of free survival (PFS) was 616 days (95% CI, 152 to 1,080 days) and overall survival (OS) was 1,161 days (95% CI, 888 to 1,434 days). Post-GC cases showed inferior PFS and OS but the difference was not significant. However, a high or high/intermediate IPI score was significantly associated with worse PFS (HR 4.96; 95% CI, 1.53 to 16.05; p=0.002) and OS (HR 4.52; 95% CI, 1.21 to 16.87; p=0.03). Conclusions: Immunohistochemical analysis provides information about subtypes of DLBCL; but, in our series, this profile was not essentially predictor of survival. Our results confirm the value of IPI score in the prognosis of patients with DLBCL. No significant financial relationships to disclose.
Quality of life after high-dose rate brachytherapy monotherapy for prostate cancer.
Authors: Jessika Contreras, Richard Wilder, Eric Albert Mellon, Tobin Joel Crill Strom, Daniel Celestino Fernandez, Matthew C. Biagioli
Journal: Journal of Clinical Oncology (2014)

278 Background: There is little information in the literature on health-related quality-of-life (HRQOL) changes due to high-dose-rate (HDR) brachytherapy monotherapy for prostate cancer. Methods: We conducted a prospective study of HRQOL changes due to HDR brachytherapy monotherapy for low risk or favorable intermediate risk prostate cancer. Forty-nine of 84 (58%) patients who were treated between February 2011 and April 2013 completed 50 questions comprising the Expanded Prostate Cancer Index Composite (EPIC) before treatment and 6 and/or 12 months after treatment. Results: Six months after treatment, there was a significant decrease (p&lt;0.05) in EPIC urinary, bowel, and sexual scores, including urinary overall, urinary function, urinary bother, urinary irritative, bowel overall, bowel bother, sexual overall, and sexual bother scores. By one year after treatment, all EPIC scores had increased and were not significantly different from baseline values. Conclusions: HDR brachytherapy monotherapy is well-tolerated in patients with low and favorable intermediate risk prostate cancer. Urinary, bowel, and sexual domain scores returned to close to baseline 12 months after treatment.