tbuckley/cabot-search huggingface dataset:
Impact of prior platinum agent and site of primary in patients with advanced urothelial carcinoma (UC) receiving salvage therapy.
Authors: Guru Sonpavde, Joaquim Bellmunt, Jonathan E. Rosenberg, Dean F. Bajorin, Ashley Marie Regazzi, Toni K. Choueiri, Angela Q. Qu, Guenter Niegisch, Peter Albers, Andrea Necchi, Giuseppe di Lorenzo, Ronan Fougeray, Yu-Ning Wong, Srikala S. Sridhar, Yoo-Joung Ko, Matthew I. Milowsky, Matt D. Galsky, Gregory Russell Pond
Journal: Journal of Clinical Oncology (2014)

336 Background: The prognostic impact of prior platinum agent (cisplatin vs. carboplatin) and site of primary (bladder vs. other) in the context of salvage therapy for advanced UC is unknown. Methods: We pooled 10 prospective phase II trials of ≥ second-line therapy for advanced UC with data recorded for prior platinum agent and site of primary in addition to major prognostic factors: TFPC (time from prior chemotherapy), Hb (hemoglobin), PS (performance status), and LM (liver metastasis) status. Cox proportional hazards regression was used to evaluate the association of prior platinum agent and site of primary with overall survival (OS) and progression-free survival (PFS). Trial was included as a stratification factor throughout. Kaplan-Meier method was used to estimate PFS and OS. Results: Of 731 patients overall, 559 had received one prior chemotherapy regimen, 663 were evaluable for prior platinum regimen and 512 for site of primary. The overall median PFS and OS were 2.7 and 6.8 months, respectively. The trials evaluated vinflunine (N=151), docetaxel +/- vandetanib (N=148), paclitaxel-gemcitabine (N=98), sunitinib (N=77), volasertib (N=50), nab-paclitaxel (N=48), everolimus (N=45), pazopanib (N=43), cetuximab +/-paclitaxel (N=39) and paclitaxel-cyclophosphamide (N=32). Prior platinum was cisplatin in 501 (75.6%) and carboplatin in the rest. Prior carboplatin was associated with worse OS on univariate analysis (HR 1.23 [1.00-1.52], P=0.048) but not significantly associated with either OS or PFS on multivariate analysis. Bladder was the site of primary in 388 (75.8%). The site of primary was not significantly associated with PFS and OS in either univariate or multivariate analyses. Conclusions: Neither prior platinum agent (cisplatin vs. carboplatin) nor site of primary (bladder vs. other) were independently associated with OS or PFS in patients receiving salvage therapy for advanced UC. Trials of salvage therapy may continue to utilize the previously recognized prognostic factors, and could allow patients with all sites of primary disease and regardless of the prior platinum agent. These data need external validation.
The impact of zoledronic acid therapy in survival of bladder cancer patients with bone metastasis.
Authors: S. Hoshi, K. Numahata, K. Ono
Journal: Journal of Clinical Oncology (2010)

e15096 Background: Bone metastases occur in almost 40% of patients with bladder cancer. M-VAC chemotherapy to bone metastasis has been done and median survival time is 10 months. (Bajorin, JCO 17, 3173, 1999). Recent studies demonstrate a direct antiproliferative effect of 3rd generation bisphosphonates (BPs) on bladder tumors, which may influence the survival. Therefore, we examined the clinical impact of zoledronic acid (ZOL; Zometa), a 3rd generation BP, with a focus on the survival, time to progression and pain effect in bladder cancer patients with bone metastases. Methods: Bladder cancer patients (n = 30, Stage IV) with evidence of metastasis bone scan were included. Fifteen patients of 30 experienced bone pain and received ZOL, 4 mg i.v. every 28 days (Group A), whereas the other 15 patients received no ZOL (Group B). All patients were treated with a combination chemotherapy consisted of gemcitabine 1000 mg/m(2) and carboplatin AUC = 6. Results: It was found that Group A had a statistically significant longer survival (p =0.003) when compared to Group B. Median survival time of Group A and Group B was 16 months and 7 months, respectively. A statistically significant positive correlation was found between the number of cycles of therapy with ZOL and total patient survival (p < 0.01, Pearson correlation) and time to progression (p < 0.01). Pain effect of ZOL had no significant difference between the 2 groups of patients (p > 0.05). Urine N-telopeptide of type I collagen (NTx) levels decreased in patients with NTx < or = 29 nM BCE/mM creatinine at baseline after treatment with ZOL. Conclusions: The results of our study suggest that the addition of ZOL increases overall survival in bladder cancer patients with bone metastases. The longer period of receiving ZOL, the better effect on survival and time to progression. Further clinical investigation is warranted. No significant financial relationships to disclose.
Pulmonary hypertension in ARDS: inflammation matters!
Authors: Laura C Price, S John Wort
Journal: Thorax (2017)

The recognition of pulmonary vascular complications in acute respiratory distress syndrome (ARDS) spans more than 40 years. Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure of ≥25 mm Hg at right heart catheterisation. PH is a recognised consequence of ARDS, with a high prevalence in early studies. The pathogenesis of PH in ARDS is likely to be multifactorial and disease stage-dependent. Further to the modifiable effects of positive pressure ventilation,1 potential underlying mechanisms of PH in ARDS include vessel obliteration, microthrombosis and pulmonary vasoconstriction due to hypoxia, hypercapnia and vasoactive mediator imbalance. Pulmonary vascular remodelling occurs later.2 Sepsis-related right-sided and also left-sided ventricular myocardial dysfunction may also contribute. Whatever the cause of PH, the resulting right ventricular (RV) dysfunction is associated with increased morbidity and mortality,3 ,4 although it is not actually proven that RV failure is a mode of death in ARDS. Trials of pulmonary vasodilators, such as inhaled nitric oxide and prostacyclin, have met with disappointment in terms of outcomes, although there is fair criticism of the design of the studies and the heterogeneity of the populations involved. Notably, these studies targeted oxygenation rather than pulmonary haemodynamics; so, any potential contribution of improved RV function to better outcomes is untested. What is clear is that outcome has improved in ARDS with a parallel apparent reduction in prevalence of PH and RV dysfunction. Both may be due to changes in ventilation practice following the landmark protective ventilation studies, as limiting ventilator airway pressures directly reduces RV dysfunction through physiological mechanisms.5 However, even with the use of ‘modern era’ lower airway pressures, RV dysfunction remains in the region of 20%–25%3 ,4 and interestingly appears to be associated with sepsis.3 So, what is the role of sepsis and, …
Oncologic impact of monocarboxylate transporter 4 (MCT4) in pancreatic cancer.
Authors: Sung Hwan Lee, Chang Moo Kang, Ho Kyoung Hwang, Woo Jung Lee
Journal: Journal of Clinical Oncology (2015)

319 Background: Transporters for monocarboxylate play an integral role in cancer metabolism in terms of the regulation of intracellular pH. The aim of our study is to check the oncologic impact of Monocarboxylate Transporter 4 (MCT4) expression in pancreatic cancer. Methods: To identify oncologic impact of MCT4 in pancreatic cancer, we performed immunohistochemical (IHC) stains for MCT4 in paraffin embedded block of resected pancreatic cancer tissue. MCT4 expression was correlated with short-term and long-term oncologic outcomes. Results: Fifty patients were enrolled to this study and formalin-fixed, paraffin-embedded (FFPE) tissue block of surgically resected pancreatic cancer and survival data were used for identify the oncologic impact of MCT4. Overall expression of MCT4 in pancreatic cancer was observed (84.5% above intensity grade 1) compared to normal pancreatic tissue in immunohistochemical stain. High expression of MCT4 was observed in twenty-two patients (44%). There were no statistical difference regarding tumor size, T-stage, N-stage, perineural invasion, lymphovascular invasion, tumor grade, R0 resection, and postoperative adjuvant treatment between high and low MCT4 expression group (p&gt;0.05). However, high MCT4 expression group showed significantly poorer cancer-specific survivals than low expression group (median survival; 15 vs. 32 months, p=0.001). Conclusions: The expression of monocarboxylate transporter 4 (MCT4) was identified as poor prognostic factor in pancreatic cancer. Further study to identify the possibility of MCT4 as a potential therapeutic target for treating pancreatic cancer is mandatory.
A phase I trial of erlotinib and bexarotene as a targeted combination therapy for aerodigestive tract cancers
Authors: K. H. Dragnev, W. J. Petty, S. Shah, M. A. Carey, W. M. Disalvo, I. Williams, J. R. Rigas, E. Dmitrovsky
Journal: Journal of Clinical Oncology (2005)

7093 Background: We previously reported the overexpression of the epidermal growth factor receptor (EGFR) and cyclin D1 as early events in lung carcinogenesis. All-trans-retinoic acid (RA) suppressed EGFR expression through a transcriptional mechanism and cyclin D1 through proteasome-dependent proteolysis. Non-classical retinoids such as the rexinoid, bexarotene (B), repress both cyclin D1 and EGFR expression but signal independent of RAR-beta, which is often deregulated in lung carcinogenesis. Combining an EGFR tyrosine kinase inhibitor, erlotinib (E), with B induced at least additive suppression of growth and cyclin D1 expression in RA-resistant human bronchial epithelial cells which had silenced RAR beta and in some lung cancer cell lines. Methods: A phase I trial of E and B was conducted in patients (pts) with advanced aerodigestive tract cancers. Primary objective - maximum tolerated dose. Secondary objectives - toxicities, efficacy, and surrogate markers of response (cyclin D1) in buccal swabs from pts at the highest dose. 3 dose levels - 1: B 300 mg/m2, E 100 mg; 2: B 300 mg/m2, E 150 mg; 3: B 400 mg/m2, E 150 mg. At least 3 pts were enrolled at each level. All pts received atorvastatin for elevated triglycerides. Results: Twenty-four pts were enrolled including 46% women and 79% with NSCLC. The median age was 61 years, 62% had first-line and 21% second line chemotherapy, one third had KPS of 70, and 67% were former smokers. Toxicities were mild with frequent hypertriglyceridemia and skin rash. No cases of pancreatitis were observed. Two DLTs were observed: CPK elevation and systemic pain. Four objective partial responses were seen in pts with NSCLC, eight pts (5 NSCLC, 3 head/neck) had stable disease. Median time to progression was 2.23 months, median overall survival was 14.1 months, and one-year survival was 59%. EGFR sequencing revealed no activating mutations in exons 18, 19, and 21 for two responding cases. Cyclin D1 protein expression was repressed in buccal swabs from 5/6 pts. Conclusions: The recommended phase II doses are erlotinib 150 mg and bexarotene 400 mg/m2 daily. This regimen is well tolerated and shows preliminary evidence of activity for the treatment of advanced aerodigestive tract cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Genentech, Ligand Genentech, Ligand
Real-world treatment patterns among patients with advanced gastric cancer in South Korea.
Authors: Gebra Cuyun Carter, Anna Kaltenboeck, Jasmina Ivanova, Astra M. Liepa, Alexandra San Roman, Maria Koh, Hyun Jung Lee, Narayan Rajan, Shaila Ballal, Howard Birnbaum, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2014)

152 Background: This study explored treatment patterns, and cancer-related resource use of patients with metastatic and unresectable gastric cancer (MGC) in South Korea. Methods: Charts of patients ≥ 18 years old were reviewed by 30 physicians to collect de-identified data on MGC or gastroesophageal junction adenocarcinoma [diagnosis on or after January 1, 2009]. Patients received platinum/fluoropyrimidine first-line therapy followed by second-line therapy or best supportive care, had no other primary cancer, and did not participate in a clinical trial following MGC diagnosis. Patient characteristics and treatment patterns were summarized using descriptive statistics. Results: Of 198 patients, 74% were male; 78% were diagnosed with MGC after age 55 (mean=61 yrs); 47% were current or former smokers and 48% reported light to moderate alcohol consumption. The majority of tumors were located in the antrum/pyloris (52%); metastatic sites most often occurred in the peritoneum (54%), lymph nodes (48%), and liver (39%). At diagnosis, the mean Charlson comorbidity index was 0.4 (std dev=0.6). The most common comorbidities were chronic gastritis (23%) and cardiovascular disease (19%). Most patients (80%) received second-line treatment (ECOG scores: 0 -10%, 1 -66%, 2 -22%); 20% received best supportive care only. Single-agent fluoropyrimidine was reported for 22% of patients receiving second-line treatment; 20% were treated with irinotecan with a fluoropyrimidine or platinum agent. Second-line treatment was chosen mainly according to national guidelines (81%) and physician experience (35%). The most common symptoms during second-line treatment were nausea/vomiting (45%) and pain (11%), with antiemetics (45%), analgesics (37%) and nutritional support (11%) most often used as supportive care. Two-thirds of inpatient hospitalizations (30% of second-line patients had ≥ one) were for chemotherapy infusion. Outpatient hospitalization (16%) and visits to the oncologist (38%) were common among second-line patients. Conclusions: Most patients received second-line treatment, though regimens varied. Understanding MGC patient characteristics and treatment patterns in Korea will help address unmet needs.
A cross sectional study on intestinal and bladder symptoms in gynecologic malignancies.
Authors: K. Pushpalatha, P. K. Julka, J. B. Sharma, K. Sunesh Kumar, K. K. Roy, D. Sharma, L. Kumar
Journal: Journal of Clinical Oncology (2010)

5115 Background: To find out the prevalence of various intestinal and bladder problems in gynaecologic malignancies as compared with benign conditions. Methods: All participants (case study group n = 200, control group n = 200) were addressed with a questionnaire covering various urinary and bowel symptoms. Between October 2008 and October 2009, 200 patients with history of gynaecologic cancer, treated with surgery, chemotherapy or radiotherapy, attending gynae cancer clinic, IRCH, AIIMS under study group and 200 patients under control group with benign gynaecological conditions were included. Results: The mean age was 50.8 years in study group and 48.8 years in control group with mean parity of 4.1 and 3.8 respectively. Among gynaecological cancers, there were cancer cervix (n = 100), ovarian cancer (n = 50), endometrial cancer (n = 30), vulvo-vaginal cancer (n = 20). Among benign cases, there were chronic cervicitis (n = 55), fibroid uterus (n = 60), pelvic inflammatory diseases (n = 35), endometriosis (n = 25),prolapse uterus (n = 25). We found increased frequency of urine (> 10 per day) (25% vs. 5.4%), nocturia (30% vs. 5.6%), burning micturition (25% vs. 3%), UTI (7.5% vs. 1.6%), urinary hesitancy (2.5% vs. 1.6%), urinary incontinence (36.5% vs. 22.4%), hematuria (15% vs. 1.7%). Among urinary incontinence, urge incontinence was seen in 1% vs. 2.9%,stress incontinence in 27.3% vs. 18%, true incontinence was seen in 7.5% vs. 0.03% and mixed incontinence in 0.7% vs. 1.47%. Among bowel symptoms, there was frequency of stool (35.8% vs. 5.3% ), constipation (30% vs. 7.4% ), gas incontinence (28.9% vs. 5.8%), incontinence of loose stools(44% vs. 2.4%), underwear soil by stool leakage(27% vs. 0.03%), use of any pads (21% vs. 0.03%), feeling of incomplete emptying (37% vs. 4.6%), return to toilet within one hour of defecation (35% vs. 0.02%), inability to defer defecation for > 10 mins (28.9% vs. 4.5%), inability to distinguish between gas and stool (25% vs. 0.03%), associated abdominal pain (30% vs. 6.5%). Conclusions: There is a high prevalence of urinary and bowel problems in gynaecological malignancies. No significant financial relationships to disclose.
Suspected immunosuppression and increased micronucleus frequency in patients with testicular seminoma 7 years after radiotherapy.
Authors: A. Fucic, M. Gamulin, J. Katic, M. Grgic
Journal: Journal of Clinical Oncology (2011)

e15075 Background: In addition to therapeutic efficiency and survival rate, the success of radiotherapy is also measured by side effects and long-term health risks. Secondary cancer incidence and immunosuppression are parameters in estimating the health risk of radiotherapy (RT) in seminoma patients (pts). Testicular seminoma pts undergo significant lymphocyte genome damage during and after radiotherapy. The aim of this study was to see if there is genome damage and immunosuppression detectible by micronucleus (MN) assay seven years after radiotherapy. Methods: This study followed up 10 testicular seminoma stage I pts aged 23-49 years who were analyzed for genome damage and mitotic index (MI) using the MN assay (Fenech, 1985) 7 years after tumour removal and RT with the total dose of 25 Gy/16 daily fractions. For reference 10 healthy, age-matched men was used. Statistical analysis of differences between the groups was performed by the Mann-Whitney U-test. Results: MN frequency in binuclear lymphocytes did not differ significantly between pts and controls (6.03/1000 vs. 4.70/1000 cells; P<0.05). Patients showed a significantly higher MN frequency in mononuclear lymphocytes (2.88/1000 vs. 0.33/1000; P<0.05 ). In addition, their MI was significantly lower than in controls (1.19 vs 1.50; P<0.05). Conclusions: This is the first study to show increased MN frequency in mononuclear lymphocytes of testicular seminoma pts 7 years after radiotherapy. Our study stresses the significance of scoring MN frequency in both mono and binuclear lymphocytes in order to avoid false findings. Detected genome instability may be related with possible secondary cancer risk. Disturbances in the mitotic apparatus and suspected immunosuppression, expressed as low MI, suggest that it is necessary to run also immunologic surveillance of cancer pts after RT. As phytohaemagglutinin is used for stimulation of T lymphocyte proliferation in MN assay, our findings of decreased MI are in concordance with depletion of CD 4 T lymphocytes reported in survivors of nuclear bomb. Future studies should investigate the possible differences in radiosensitivity between lymphocyte subtypes in these pts and health risks they involve.
Multimodal analgesia combined with intravenous administration of acetaminophen in perioperative management of esophagectomy using modified ERAS protocol.
Authors: Takashi Ogata, Tetsushi Nakajima, Kazuki Kano, Kenki Segami, Yukio Maezawa, Tsutomu Sato, Haruhiko Cho, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2016)

94 Background: In perioperative management of esophagectomy, we have performed modified ERAS protocol including preoperative oral rehydration, early enteral nutrition, early mobilization, intestinal peristalsis promotion, pain control, and so on. We think these elements are related closely and useful in reducing complication and early recovery after surgery in case of high invasive surgery such as esophagectomy with 3 field lymph node dissection. And we think pain control is particularly close relationship with early mobilization, so multimodal analgesia is very important for postoperative pain control. Methods: We evaluated whether it is possible to reduce postoperative breakthrough pain by using postoperative pain control combined with acetaminophen IV. 124 patients were treated by esophagectomy with 3-field LN dissection from January 2013 to June 2015. Before May 2014, 49 patients were treated without acetaminophen IV protocol (Group A), and after May 2014, 75 patients were treated with acetaminophen IV protocol (Group B). We compared the number of analgesic drug until postoperative day 7, and compared the ratio of liver dysfunction in both groups. Both groups were used epidural anesthesia as postoperative pain management, and intravenous administration of acetaminophen 1000mg/day has been added between day3 to day 7 in Group B. Results: The number of analgesic drug use due to breakthrough pain(Group A / Group B) were day3:1.12/0.55, day4:1.58/0.83, day5:1.76/0.57, day6:1.24/0.49, and it was reduced significantly in Group B (p &lt; 0.01). And liver damage as a side effect by acetaminophen IV, the rise of ALT(Group A / Group B) were seen 32.7%/66.7% in day6, and seen 20.4%/62.7% in day 8, and it was significantly higher in Group B at day6 and day8 (p &lt; 0.01), but was no significant difference in day 30 between both groups. Conclusions: In perioperative management of esophagectomy, pain control combined with acetaminophen IV was useful as multimodal analgesia. Also was ALT rise is seen by liver damage, but it was the minor change in the acceptable range for natural healing.
Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in the CLEOPATRA study.
Authors: Michael Ewer, José Baselga, Emma Clark, Mark Benyunes, Graham Ross, Sandra M. Swain
Journal: Journal of Clinical Oncology (2012)

533^ Background: Addition of trastuzumab (T) to chemotherapy has transformed outcomes in pts with HER2-positive breast cancer. In pts who had received anthracyclines (A), T has been associated with cardiac dysfunction. Monitoring cardiac tolerability of anticancer drugs is important, including that of a new regimen combining T with a second anti-HER2 antibody that inhibits HER2 dimerization, pertuzumab (P). In CLEOPATRA, efficacy and safety of P+T+docetaxel (D) were studied in HER2-positive 1 st -line MBC (Baselga 2012). Methods: CLEOPATRA, a randomized, double-blind, placebo-controlled, ph III trial, enrolled 808 pts; 804 were included in the safety population. A baseline (BL) LVEF ≥50%, no history of congestive heart failure, and no LVEF decline to &lt;50% during/after prior T were required. Treatment was administered q3w until disease progression or unmanageable toxicity (P/placebo [Pla]: 840 mg, followed by 420 mg; T: 8 mg/kg, followed by 6 mg/kg; D [≥6 cycles recommended]: 75 mg/m 2 , escalating to 100 mg/m 2 if tolerated). LVEF was assessed by ECHO or MUGA at BL, every 9 wks during treatment, at discontinuation, and up to 3 yrs thereafter. Adverse events (AE) were monitored continuously and graded according to NCI-CTCAE v3.0. Results: The incidence of any cardiac disorder (grade ≥1) as assessed by the investigators was similar with Pla+T+D (16.4%) and P+T+D (14.5%). LVSD (grade ≥1) was the most frequent cardiac AE and more common with Pla+T+D. At the time of data cutoff for this analysis, 8/11 symptomatic LVSD events had resolved; none fatal. All pts who developed symptomatic LVSD had ≥1 potential cardiac risk factor (prior A, prior T, radiation, smoking, diabetes, hypertension, other). Compared to the overall pt population, only prior A and radiation were higher in pts who developed symptomatic LVSD. Conclusions: CLEOPATRA provides evidence that P+T+D does not increase overall cardiac disorders, specifically symptomatic LVSD, compared to Pla+T+D. [Table: see text]