tbuckley/cabot-search huggingface dataset:
Changes in cervical cancer course under the influence of HPV/chlamydia trachomatis co-infection.
Authors: Nailya Guskova, Elena Mikhaylovna Frantsiyants, Valeria Bandovkina, Tatiana Moiseenko, Marina Vovkochina, Natalia D. Cheryarina, Yulia A. Pogorelova, Ekaterina Guskova, Marina I. Vereskunova, Kristina Avanesova, Irina V. Tselishcheva, Nadezhda Golomeeva, Svetlana V. Abakumova, Viktoria Zakharchenko, Svetlana V. Belgova, Anastasia Nozdricheva, Ekaterina Gornostaeva
Journal: Journal of Clinical Oncology (2017)

e17018 Background: The purpose of the study was to analyze the effect of HPV/Chlamydia trachomatis co-infection on the hormonal status of tumor and visually unchanged cervical tissues in cervical cancer patients. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4) and prolactin (PRL) by the ELISA in tumors and visually unchanged cervical tissues of 49 patients with cervical cancer T1b-2aN0M0 with endophytic (25 patients) and exophytic (24 patients) patterns of tumor growth. 13 patients with endophytic tumors and 12 patients with exophytic ones were infected with HPV and Сhlamydia trachomatis (Ch.tr.). HPV infection was determined by Е7 protein expression, Ch.tr. – by IgG and IgА and antigen/DNA in ELISA and PCR. Intact cervical tissues obtained during hysterectomy from 22 non-infected women with endometrial cancer were used as the control. Results: Tumor tissues of the cervix without infection demonstrated increased levels of all sex steroids: estrogens by 3 times, androgens by 3.1 times and progestins by 1.8 times. Co-infected tissues were characterized by the sex-steroid imbalance. We observed reduced coefficients of estrogens to T and fT by 1.6 and 6 times, respectively, compared to intact tissues (most significant in a tumor with endophytic growth pattern) and an increase in the estrogens to P4 ratio by 1.5 times – only in endophytic growth pattern. Androgenic status in co-infected tumor tissues increased by 1.7 in endophytic and by 3.1 times in exophytic growth pattern. PRL level was increased only in co-infected tumors (by 2.5 times). Unchanged co-infected tissues, unlike non-infected samples, showed E2 increase by 2.6 times in exophytic and by 1.5 times in endophytic growth pattern, T increase by 1.6 times only in endophytic tumors and P4 decrease by 1.5 times and PRL increase by 1.8 times regardless the tumor growth pattern. Conclusions: Hormonal profile of both tumor and unchanged cervical tissues was dependent on HPV/Ch. tr. co-infection and tumor growth patterns. The changes could result from HPV and Ch. tr. interaction triggering malignant processes.
Effect of radiotherapy treatment modalities on survival in stage IIa prostate cancer: A National Cancer Data Base (NCDB) analysis.
Authors: Timothy Dean Malouff, Sydney Marsh, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2016)

5069 Background: Radiation therapy remains one of the most effective methods of treating stage IIA prostate cancer. Several retrospective studies have determined that external beam radiation therapy (EBRT) or brachytherapy (BT) are equivalent to prostatectomy for survival. Although a recent retrospective cohort study showed no significant difference in external and internal radiation when using a biochemical endpoint, there are few studies with a survival endpoint. To our knowledge, we are the largest retrospective analysis comparing EBRT and BT with a survival endpoint in stage IIA prostate cancer. Methods: Using the National Cancer Data Base, we analyzed 122,405 patients with stage IIA prostate cancer who underwent radiation therapy for treatment of the primary tumor between 2004-2013 and had sufficient survival data. Patients with previous hormone therapy or surgery were excluded. EBRT includes any form of external radiation. BT consists of any method of internal radiotherapy. Combination therapy (CT) refers to any combination of external and internal radiotherapies. Survival was determined by time of diagnosis to time of last contact or death. A Kaplan-Meier curve was constructed and pairwise comparisons were performed using the log-rank test. Results: The average ages for EBRT, BT, and CT are 69, 66, and 66, respectively. The average PSA scores were 12.1, 11.9 and 15.0 ng/ml. There was no difference in Charlson comorbidity index between groups, with an average score of less than 0.15. The average tumors in EBRT and BT were characterized as moderately differentiated, while CT was poorly differentiated. There was a significant difference in survival for EBRT vs BT (p<0.001) and EBRT vs CT (p<0.001). There was not a significant difference between patients treated with CT and BT alone (p=0.673). Conclusions: The method of radiotherapy used contributes to the survival of patients with stage IIA prostate cancer, with brachytherapy with or without EBRT having improved survival. Careful selection of the proper treatment regimen should be used. Survival data. Modality Patients Treated Average Survival (Months) 10-year Survival EBRT 54.3% 109 61.5% BT 35.2% 116 72.9% CT 10.4% 116 73.1%
Immunosenescence in testicular cancer survivors treated with chemotherapy.
Authors: Maria Teresa Bourlon, Hugo Eduardo Velazquez, Juan Hinojosa, Guadalupe Lima, Ricardo Rios-Corzo, Karina Jimenez-Martinez, Gabriela Zarco-Letzel, Luis Llorente, Yemil Atisha-Fregoso
Journal: Journal of Clinical Oncology (2017)

e16037 Background: Cytotoxic (Ctx) chemotherapy can cure patients with advanced testicular cancer. Notwithstanding, Ctx agents could promote molecular aging and induce cellular senescence in vivo. This phenomenon has been studied in breast cancer patients exposed to adjuvant chemotherapy, however, the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy remains unknown. Methods: Case-control study. Cases were 18-55 yo TCS, treated with chemotherapy (≥3 BEP cycles), disease-free for ≥3 m. Controls were healthy subjects matched by sex and age ± 1 y. Selected subpopulations of isolated peripheral blood mononuclear cells (PBMC) depicted in Table, were analyzed flow cytometry. Statistics: Adjusted counts or relative percentage for each population were compared using student-t test or Mann-Whitney U test as appropriate. Results: We included 15 TCS and 15 controls. Mean age was 32.6 yo (24-54 y). Mean time since last chemotherapy was 53.13 months (3-192 m). All 15 patients were treated with at least 3 BEP cycles ± TIP/VIP cycles. There were no differences in total leucocyte (5128 ± 1917 vs 5850 ± 2141, p=0.36), and lymphocyte (1539 ± 592 vs 1889 ± 825, p=0.4) counts among cases and controls. Cases have a diminished percentage of CD3+ (63 ± 10 vs 71 ± 11, p=0.05) and CD4+ cells (36±8 vs 43 ± 9, p=0.03). There were no differences in pct of CD8+ or CD19+. However, there was an increase in late differentiated CD8+/CD57+ cells (31 ± 14% vs 20 ± 11%, p=0.02); and a decrease in CD4+/CD28+ cells (90 ± 9% vs 97 ± 4%, p=0.02) in cases. We observed paradoxical changes in B cell subpopulations with an increment in naïve (79 ±10 vs 67% ± 14% p=0.02) and a decrease in memory (18 ± 9 vs 31 ± 13%, p=0.01) B cells. Conclusions: TCS after chemo develop changes compatible with immunesenescence in T cell (CD3+) compartment, and an increment in naïve B cells. [Table: see text]
Evaluation of anthracycline incuced cardiotoxicity by speckle tracking echocardiography.
Authors: Atalay Dogru, Devrim Cabuk, Tayfun Sahin, Ilhan Dolasik, Kazim Uygun
Journal: Journal of Clinical Oncology (2013)

e11585 Background: Anthracyclines have been widely used in the treatment of solid and hematologic malignancies. Cardiotoxicity is the most serious adverse effect that limits anthracycline treatment. Cardiotoxicity is classified by time of onset as acute, subacute and chronic. Conventional echocardiography is not sensitive enough for early detection of cardiotoxicity. In this study we aimed to evaluate anthracycline induced cardiac toxicity by speckle tracking echocardiography (STE) before left ventricular dysfunction occurs. Methods: The study included newly diagnosed breast cancer (BC) and lymphoma patients (pts) who were treated with an anthracycline containing chemotherapy (CT) regimen. They had examination with conventional echocardiyography, STE before and after anthracycline treatment. Longitudinal strain values were assessed by automated function image (AFI). Results: Thirty five pts with BC and 15 pts with lymphoma were included in the study. Ejection fraction (EF) and fractional shortening values were decreased in lymphoma pts receiving high dose anthracycline treatment (346 mg/m 2 ) compared to BC pts receiving low dose (168 mg/m 2 ) anthracycline. There was statistically significant increase in myocardial performance index in both groups after anthracycline CT (p=0.001 and p=0.004 for BC and lymphoma group respectively). In STE measurements, apical long axis, apikal 4 chamber and global peak systolic strain showed significant reduction in lymphoma group who had a post-therapy EF &lt;55% (p=0.002, p=0.041, and p=0.004, respectively). Apical long axis and global peak systolic strain were also significantly decreased among the lymphoma pts with normal systolic function after CT (p=0.01 and p=0.05, respectively). Conclusions: STE can display the effect of anthracycline induced cardiotoxicity early before left ventricular dysfunction occurs. Larger prospective studies are needed to verify these data and direct the treatment of pts receiving anthracycline.
Association of plasma cell-free DNA concentration [cfDNA] with outcome from taxane therapy (TT) for castration resistant prostate cancer (CRPC).
Authors: Niven Mehra, Rossitza Christova, Lorna Pope, Suzanne Carreira, Jane Goodall, David Lorente, Nuria Porta, Emma Hall, Penelope Flohr, Gunther Boysen, Diletta Bianchini, Oliver Sartor, Mario A. Eisenberger, Karim Fizazi, Stephane Oudard, Mustapha Chadjaa, Sandrine Macé, Johann S. De Bono
Journal: Journal of Clinical Oncology (2016)

5014 Background: Biomarkers are needed to guide CRPC treatment; we evaluated [cfDNA] pre- and post-TT, associating this with outcome. Methods: cfDNA was isolated and quantified from 1 mL of plasma, prospectively collected from CRPC patients (PTS) recruited to two phase III trials, utilizing QIAamp Circulating Nucleic Acid and Quant-IT Picogreen HS DNA kits. FIRSTANA (NCT01308567) compared docetaxel (D; 75mg/m2) with cabazitaxel (C; 20 or 25mg/m2) as 1st line TT; PROSELICA (NCT01308580) compared C at 20 or 25 mg/m2 as 2nd line TT. Results: 1400 samples from 315 FIRSTANA PTS and 1102 samples from 256 PROSELICA PTS were available. PTS with two baseline (BL) samples (taken 1-7 days apart prior to course 1 pre-TT), had a median coefficient of variation (CV) of 23.6%, with higher median [cfDNA] in 2nd line PTS (28.4 vs 16.2 ng/mL, p<0.001) and in PTS with visceral disease (27.5 vs 19.6 ng/mL, P=0.003). Prognostic factors associated with BL [cfDNA] included Hb (Spearman r=-0.45, n=570), LDH (r=0.40, n=566), ALP (r=0.37, n=570) and PSA (r=0.34, n=566), all p<0.001. In both studies the association of BL cfDNA with OS and rPFS was stronger than that of C2 and C4 changes. Median OS by BL [cfDNA] quartiles in FIRSTANA was 38.8, 29.9, 21.8 and 15.1 months (m) and in PROSELICA 18.1, 17.8, 12.1 and 9.3m. In FIRSTANA median rPFS by BL [cfDNA] quartiles was 16.8, 11.4, 9.7, and 10.8m, and in PROSELICA 16.4, 10.3, median not reached and 10.1m. The Table reports univariate (UVA) and multivariate (MVA) Cox regression analyses for BL [cfDNA] and outcome. 95% of PTS have sufficient cfDNA (>5ng/mL) for targeted next generation sequencing (NGS). Conclusions: High BL [cfDNA] associates with advancing disease, poor prognosis and shorter rPFS on TT. NGS of these samples is ongoing to further elucidate the clinical utility of cfDNA biomarker studies. Clinical trial information: NCT01308580 and NCT01308567.BL cfDNA (log10) UVA MVA† HR 95%CI P HR 95%CI P FIRSTANA OS 3.3 2.4-4.4 <0.001 2.0 1.4-3.0 0.001 rPFS 2.2 1.6-3.0 <0.001 2.0 1.3-2.9 0.001 PROSELICA OS 1.8 1.5-2.2 <0.001 1.5 1.1-2.2 0.023 rPFS 1.6 1.2-2.1 <0.001 1.3 0.9-2.0 0.208 Combined OS 3.1 2.6-3.8 <0.001 1.6 1.2-2.1 0.002 rPFS 2.4 1.9-3.0 <0.001 1.7 1.2-2.3 0.001 † Included ECOG, M1-site, Hb, Neu, Lym, Plt, ALP, Alb, LDH, PSA, BL pain.
Incidence and predictors of hypoalbuminemia in Indian patients with breast and cervical cancer.
Authors: Anubha Bharthuar, Samridhi Sharma, Shamit Chopra, Vikram Bansal
Journal: Journal of Clinical Oncology (2018)

e22197 Background: Serum albumin is a surrogate marker of the nutritional adequacy in an individual. In the Indian cancer patient socio-economic factors impact both access to cancer care and feasibility of therapy, as patients with inadequate nutrition may have increased treatment related adverse effects and inferior survival. With this background we decided to assess the incidence of hypoalbuminemia(HA; albumin < 3.5gm/dL) in Indian breast and cervical cancer patients undergoing chemotherapy (CT) and identify factors associated with the same. Methods: We performed an observational study from 1st March to 30th May 2017 where breast and cervical cancer patients were interviewed at the start of CT and 3 weeks later. Patients’ demographic and clinical information were obtained from their respective charts. They also had assessment of dietary practices, calculation of baseline protein intake and were provided dietary counseling. Results: The study included 65 patients. Median age 55 yrs (range 32-79 yrs).Median Weight 65 Kg (range 31-93 Kg). Average BMI 26.1. Despite normal/obese BMI (63/65 patients); 47.6% (30/63) had evidence of HA. Age, cancer site, clinical setting (adjuvant/definitive vs palliative), BMI, income, residence (rural vs urban), family type (joint vs nuclear), dietary practice (vegetarian vs non-vegetarian) were not significantly associated with HA. Stage (early vs advanced) was significantly associated with HA (p = 0.01) as was baseline hemoglobin < = 10gm/dL(p = 0.009). Despite apparent adequate protein intake at baseline 37.5 %(12/32) had albumin < 3.5gm/dL. Patients with serum albumin > = 3.5gm/dL at baseline had significantly lower probability of decrease in albumin as compared to those who had albumin < 3.5gm/dL (p = 0.04). Conclusions: A significant number of our breast and cervical cancer patients had evidence of HA at baseline. HA may exist despite a normal BMI and adequate protein intake. Such patients need to be identified at the outset and aggressive measures implemented to prevent deterioration of their nutritional status and decrease chemotherapy related morbidity and mortality. These patients require frequent follow-up and repeated counseling during therapy.
Atezolizumab (atezo) in first-line cisplatin-ineligible or platinum-treated locally advanced or metastatic urothelial cancer (mUC): Long-term efficacy from phase 2 study IMvigor210.
Authors: Arjun Vasant Balar, Robert Dreicer, Yohann Loriot, Jose Luis Perez-Gracia, Jean H. Hoffman-Censits, Daniel Peter Petrylak, Michiel Simon Van Der Heijden, Beiying Ding, Xiaodong Shen, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2018)

4523 Background: Platinum-based chemotherapy is a standard first-line approach for mUC, but many pts are ineligible for cisplatin, and progression is common. Atezo (anti–PD-L1) was approved for first-line cisplatin–ineligible and platinum-treated mUC pts following IMvigor210 results. Here we present more mature DOR and OS data in both populations. Methods: Cohort 1 (NCT02951767) pts were treatment naive for mUC, had ECOG PS ≤ 2 and were ineligible for cisplatin by at least one of the following: GFR > 30 and < 60 mL/min, ≥ G2 hearing loss or peripheral neuropathy or ECOG PS 2. Cohort 2 (NCT02108652) pts progressed after platinum and had ECOG PS ≤ 1 and GFR ≥ 30 mL/min. Atezo 1200 mg IV q3w was given until PD (Cohort 1) or loss of clinical benefit (Cohort 2). We evaluated the following efficacy endpoints: RECIST v1.1 ORR by central review (primary), DOR, OS. Results: 119 Cohort 1 pts (median follow-up, 29 mo) and 310 Cohort 2 pts (median follow-up, 33 mo) were evaluable as of July 12, 2017. In Cohort 1, ORR was 24% (95% CI: 16, 32), CR rate was 8%, and median DOR was not reached (95% CI: 30.4 mo to not estimable; 19 of 28 responses ongoing); in elderly pts (≥ 80 y; Cohort 1, n = 25), ORR was 28% (95% CI: 12, 49), and CR rate was 12%. Further characterization of outcomes in pts ≥ 80 y and subgroups with poor prognostic factors will be presented. In Cohort 2, ORR was 16% (95% CI: 13, 21), CR rate was 7%, and median DOR was 24.8 mo (95% CI: 13.8, 30.4). In both cohorts, sustained responses occurred among pts who discontinued atezo for reasons besides PD. In Cohort 1, median OS was 16.3 mo (95% CI: 10.4, 24.5), with 1-y OS of 58% (95% CI: 49, 67) and 2-y OS of 41% (95% CI: 32, 50); in Cohort 2, median OS was 7.9 mo (95% CI: 6.7, 9.3), with 1-y OS of 37% (95% CI: 31, 42) and 2-y OS of 23% (95% CI: 19, 28). Conclusions: With > 2 y median follow-up, responses to first-line atezo in cisplatin-ineligible mUC pts, including pts ≥ 80 y, appeared durable, resulting in continued improvement in OS since the primary analysis. For pre-treated pts, ORR and OS were in line with prior data, and taken together with DOR, data were consistent with Ph 3 results (IMvigor211, NCT02302807). Clinical trial information: NCT02951767 and NCT02108652.
TCT-562 Chemical Renal Denervation With Alcohol – The Post-Market Study Data And The Target BP Program
Authors: Felix Mahfoud, Sebastian Ewen, Alexandre Persu, Jean Renkin, Wojtek Wojakowski, Roland Schmieder, Markus van der Giet, Maximilian de Bucourt, Andreas Zirlik, Nicole Haratani, Helen Parise, Tim Fischell, Stefan Bertog, Kolja Sievert, Horst Sievert
Journal: Journal of the American College of Cardiology (2018)
TCT-341 Results of percutaneous coronary intervention in restenosis lesions with second-generation paclitaxel coated balloons at a long-term follow-up.
Authors: José Abellán-Huerta, Ignacio Sanchez-Perez, Fernando Lozano, Alfonso Jurado-Román, Juan Antonio Requena, Ramón Maseda Uriza, María López-Lluva
Journal: Journal of the American College of Cardiology (2018)
Neoadjuvant chemo/immunotherapy for the treatment of stages IIIA resectable non-small cell lung cancer (NSCLC): A phase II multicenter exploratory study—NADIM study-SLCG.
Authors: Mariano Provencio-Pulla, Ernest Nadal-Alforja, Manuel Cobo, Amelia Insa, Marinha Costa Rivas, Margarita Majem, Delvys Rodriguez-Abreu, Guillermo Lopez-Vivanco, Manuel Domine, Elvira Del Barco Morillo, Bartomeu Massuti, Rosario Garcia Campelo, Alexandre Martinez Marti, Reyes Bernabé, Fernando Franco, Maria Jove, Ricardo Arrabal, Paloma Martin, Joaquin Casal, Virginia Calvo
Journal: Journal of Clinical Oncology (2018)

8521 Background: The combination of chemotherapy and immunotherapy (CT-IO) has a high response rate and longer survival in unselected patients (pts) with metastatic non-small cell lung cancer (NSCLC). There are no data about this combination in the neoadjuvant setting. Methods: A Phase II, single-arm, open-label multicenter study of resectable stage IIIA N2-NSCLC adult patients with CT plus IO (nivolumab (NV)) followed by adjuvant treatment for 1 year. Neoadjuvant treatment: Three cycles of NV 360mg IV Q3W + paclitaxel 200mg/m2 + carboplatin AUC 6 IV Q3W. After completing neoadjuvant therapy, tumor assessment is performed in patients prior to surgery. Surgery is performed in the 3rd or 4th week after day 21 of the third cycle of neoadjuvant treatment. Adjuvant treatment: nivolumab 240mg IV Q2W for 4 months and nivolumab 480mg IV Q4W for 8 months (total one year) after surgical resection. The study aims to recruit 46 pts. The primary endpoint is Progression-Free Survival (PFS) at 24 months. Efficacy is explored using objective pathologic response criteria. We present preliminary data on patients that completed 3 cycles and underwent surgical assessment. Results: At the time of submission, 30 pts had been included and 13 underwent surgery. CT-IO was well-tolerated and surgery was not delayed in any patient. None of the pts withdrew from the study preoperatively due to progression or toxicity. Thirteen surgeries had been performed and all tumors were deemed resectable. 9 cases (69.2%) achieved complete pathologic response (CPR) (CI 95% 38.6-90.9%), and 2 had a major pathologic response (MPR),defined as < 10% viable tumor cells in the resection specimen. Considering both CPR and MPR, the overall response rate was 84.6% (95% CI 54.6-98.1%). Conclusions: This is the first multicentric study testing CT-IO in the neoadjuvant setting with promising antitumor activity. Neoadjuvant CT-IO with nivolumab in resectable IIIA NSCLC yields a complete pathologic response rate that has never been seen previously. The data will be updated at the time of the congress. EudraCT Number: 2016-003732-20 Clinical trial information: NCT03081689.
Thyroid dysfunction in disguise and treatment-related fatigue in the spotlight among metastatic colorectal cancer patients receiving regorafenib: Implications for clinical management.
Authors: Laura Orgiano, Fabiana Pani, Valeria Pusceddu, Giorgio Astara, Clelia Madeddu, Elena Massa, Alessio Cubeddu, Laura Demurtas, Alessandra Dessì, Eleonora Lai, Roberta Mascia, Simona Tolu, Grazia Pusole, Marco Puzzoni, Francesco Boi, Stefano Mariotti, Mario Scartozzi
Journal: Journal of Clinical Oncology (2016)

e15004 Background: Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved for the treatment of patients with metastatic colorectal cancer failing fluoropyrimidine-based chemotherapy in combination with oxaliplatin and irinotecan, bevacizumab and anti EGFR antibodies (if RAS wild type).The toxicity profile includes several side effects which make challenging the use of regorafenib in the clinical practice. Among these, thyroid dysfunctions although uncommon, might be relevant for their clinical implications. Methods: From November 2015, 14consecutive patients (4 males and 10 females; mean age 64±8.1) with metastatic colorectal cancer were studied at the start of regorafenib and at monthly intervals. In all cases a full haemogram, LDH, phosphocalcic metabolism levels (calcemia, phosphorous, parathormon, albumin, Vitamin D), FT3, FT4 and TSH were measured together with clinical assessment and thyroid morphology. Results: Fatigue represented the most commonside effect: 13/14 patients (92.8%) presented G1-G3 fatigue. Among all 5 patients developing G3 fatigue we also observed hypothyroidism (TSH 5.8±3.1, range 18.47-6.99). Interestingly 40% of patients showing G3 fatigue and hypothyroidism developed TPO Antibodies. Furthermore, in these patients we observed a trend towards a reduced phosphoremia (range 3.0-2.7; (p = ns) associated with a reduction of 25OH- Vit D. All patients who developed hypothyroidism received hormone replacement therapy with a prompt improvement of clinical symptoms, without regorafenib interruptions or dose modifications. Conclusions: These preliminary data suggest that in a non-negligible proportion of patients developing severe fatigue during regorafenib an accompanying hypothyroidism may be present. An early diagnosis and management of hypothyroidism is therefore mandatory for an effective clinical control of fatigue in most of the cases, in order to prevent unnecessary regorafenib dose reductions and modifications. Further and larger data are needed to confirm this hypothesis through a closer collaboration with endocrinologists in clinical practice.