tbuckley/cabot-search huggingface dataset:
Does severity of underlying chronic liver disease (CLD) affect treatment outcome of hepatocellular carcinoma (HCC) patients undergoing systemic chemotherapy (CT)?
Authors: W. Yeo, F. K. Mo, E. P. Hui, K. C. Lam, W. M. Ho, J. Koh, B. Ma, T. Mok, A. Chan, S. L. Chan
Journal: Journal of Clinical Oncology (2009)

e15513 Background: HCC is a common cause of morbidity and mortality. CT has been one of the treatments offered to patients (pts) who are not candidate of curative surgery. Treatment of HCC could be complicated by underlying CLD. In this study, we aimed to assess pre-CT severity of CLD on treatment outcome of HCC pts who were entered into our previously reported phase III prospective randomized CT study (J Natl Cancer Inst 2005). Methods: The severity of CLD for each pt was arbitrary assessed by adopting the Child-Pugh's classification. Patients’ characteristics were compared. Treatment outcomes in terms of responses, survival and treatment-related toxicities (NCI CTC) were compared. Results: 160 were Child's A; 28 were Child's B. Proportion of pts with cirrhosis (45% vs 71%, P=0.01) and pre-CT bilirubin level (11 vs. 15 umol/l, p=0.02) were significantly higher, while age (52 vs 45 yrs, p=0.05) and albumin level (35 vs 30 g/l, p&lt;0.0001) were significantly lower among Child's B pts. For Child's A and B pts: the median no. of CT cycles received were 4.0 vs 2.5 (p=0.01), the response rates were 17% vs 8.3% (p=0.28), the median survival were 21 vs 10.7 months (p= 0.002). When toxicity during CT were compared, Child's B pts had significantly higher rate of grade 3/4 neutropenia (0.6% vs. 7.1%, p=0.05), hyperbilirubinaemia (11.9% vs. 28.6%, p=0.02), hyponatremia (3.1% vs. 3.6%, p=0.001) and gastrointestinal bleeding (3.1% vs. 17.9%, p=0.001). Conclusions: Child's B HCC pts experienced increased treatment-related toxicities during CT. This has probably led to a shorter duration of CT and a lower response rate to CT. Their shorter survival could also be attributed to the severity of underlying CLD. Future trials on systemic therapy in HCC patients may need to consider stratifying patients according to severity of CLD. No significant financial relationships to disclose.
Abstract 13345: Programmed Necrosis Mediates Adverse Remodeling after Myocardial Infarction
Authors: Mark Luedde, Natalie Carter, Matthias Lutz, Justyna Sosna, Dieter Adam, Hans-Joerg Hippe, Mathias Heikenwaelder, Norbert Frey
Journal: Circulation (2012)

Objective: Programmed necrosis (necroptosis) represents a newly identified mechanism of cell death combining features of both apoptosis and necrosis. Like apoptosis, necroptosis is tightly regulate...
Capecitabine-based chemotherapy versus primary treatment for patients with advanced stages of undifferentiated nasopharyngeal carcinoma (UCNT): Preliminary results of a phase II study
Authors: H. Djedi, K. Bouzid
Journal: Journal of Clinical Oncology (2009)

e17049 Background: The combination of cisplatin and 5-fluorouracil (5-FU) is considered to be the standard treatment in induction chemotherapy for patients with undifferentiated nasopharyngeal carcinoma (UCNT). Capecitabine is an oral fluoropyrimidine. The aim of our study is to evaluate overall response and toxicity of this drug as a primary chemotherapy based-regimen for patients with advanced stages of UCNT. Methods: From January 2008 through December 2008, 34 chemo-naives patients with UCNT were included, mean age: 45.2 years (range 14–61 years), 12F/22M. One patient was stage IIB, nine patients stage III, 17 patients stage IVA, five patients stage IVB, and two patients stage IVC. All patients received at least 3 to 4 courses of neoadjuvant chemotherapy. The treatment plan included cisplatin at dose of 75 mg/m2 on D1 every 21 days, followed by capecitabine at a dose of 1,000 mg/m2 twice daily from D2 to D 15, with a 1-week rest period. Five patients received this scheme plus docetaxel at a dose of 75 mg/m2 on D1 with prophylactic granulocyte colony stimulating factors: lenograstim or filgrastim. All patients had a clinical evaluation of objective response and toxicity before at each cure . A CT scan was done at the end of treatment before radiotherapy. Results: After a total of 114 courses, all patients (34 pts) were evaluable for toxicity and 26 patients were evaluable for response (8 pts have not yet achieved their treatment). A clinical benefit was obtained for all patients since the first cure of chemotherapy. The overall objective response (CR+PR) was achieved in 96% of cases (25/26pts ), one patient had a stable disease. One of the two patients with stage IVC had a complete response on hepatic metastasis after 3 cures. Grade 3/4 toxicity included: diarrhea 5.2%, nausea/vomiting: 9.6%, hand-foot syndrome 3.5%, febrile neutropenia 4.3%, cardiac toxicity: 0.8%, thrombocytopenia 1.75%. Chemotherapy was interrupted for one patient after only one cure because of the cardiac toxicity. Conclusions: Capecitabine based chemotherapy is a safety and an effective regimen in patients with UCNT. However a longer follow-up is needed to confirm the benefit on disease-free survive (DFS) and overall survivor. No significant financial relationships to disclose.
CYTAR: A randomized clinical trial evaluating the preventive effect of doxycycline on erlotinib-induced folliculitis in non-small cell lung cancer patients.
Authors: G. Deplanque, J. Chavaillon, A. Vergnenegre, L. Falchero, G. Fraboulet, R. Gervais, B. Taviot, P. J. Souquet, C. Robert, O. Chosidow
Journal: Journal of Clinical Oncology (2010)

9019 Background: The most common toxicity with EGFR inhibitors is folliculitis (acneiform rash) which may have a negative impact on quality of life and treatment compliance. Several reports have suggested that doxycycline is effective in preventing or reducing the severity of these cutaneous reactions. No controlled trials evaluating this strategy have been reported in non-small cell lung cancer (NSCLC). Methods: This open label, prospective, stratified, randomized trial assessed the effect of doxycycline in reducing the incidence of erlotinib-induced folliculitis during the first 4 months of treatment (primary endpoint) and its severity (secondary endpoint). Patients with advanced NSCLC to be treated with erlotinib after failure of 1st- line chemotherapy were eligible. Patients were randomly assigned to erlotinib 150 mg with (arm A) or without (arm B) oral doxycycline 100 mg/d and were monitored for folliculitis, skin specific quality of life index, and other adverse events (AE) using the Common Terminology Criteria for Adverse Events v3.0 (CTC AE). Serial photographs were taken for blind review. To detect a 25% absolute difference in folliculitis incidence in favor of arm A (50% vs. 75%) with a 5% significance threshold and 80% power, 73 patients per arm were required. Results: Between November 2007 and January 2009, 147 patients were included. Groups were comparable for baseline characteristics. Folliculitis incidence was 71% in arm A and 82% in arm B in the intent to treat (ITT) population (p = 0.117). Incidence was 68% in arm A vs. 82% in arm B (p = 0.055) when patients randomized to arm A who did not take doxycycline were excluded from analysis. Doxycycline decreased folliculitis severity: proportions of grade 1/2/3/4 CTC AE were 61/35/4/0% in arm A versus 18/62/18/2% in arm B (p<0.001). Doxycycline was also associated with a significant decrease in the severity of other cutaneous AEs (p = 0.006). Noncutaneous AEs and serious AEs (SAE) were comparable across the 2 groups and no doxycycline-related SAE was observed. Conclusions: Doxycycline did not significantly reduce the incidence of erlotinib-induced folliculitis, but significantly reduced their severity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Roche
A new approach for the treatment of adrenal cancer: Testing an adrenal-specific adenovirus suicide gene therapy vector in an adrenal cancer xenograft model system
Authors: Merrill Goldsmith, William Waud, Tito Fojo
Journal: Cancer Research (2007)

3312  Although adrenal cortical cancer affects only a small number of patients and is initially responsive to treatment, the majority of patients eventually succumb to their disease. Therefore new approaches to treatment of adrenal cancer are needed. To develop a new therapy for adrenocortical cancer, we constructed an adrenal-specific adenoviral construct encoding the suicide gene thymidine kinase. We previously demonstrated preferential expression in adrenal cancer cells of constructs driven by the CYP11B1 (11β-hydroxylase) promoter. CYP11B1 directs the synthesis of the final enzyme in cortisol synthesis. Inserting the enhancer element of the P450scc (cholesterol side chain cleavage) gene, that catalyzes the first step in steroid hormone synthesis, further increased adrenocortical preference and strength of expression. In vitro in the presence of the prodrug ganciclovir the adrenal-specific adenovirus is preferentially cytotoxic to adrenal cancer cells. To test the adrenal-specific adenovirus in vivo, we developed an adrenal xenograft model system using the human NCI-H295R adrenal cancer cell line. This adherent line retains many adrenal characteristics. The cells in matrigelTM were implanted in NOD-SCID mice and xenografts formed in all of the engrafted mice and grew to 400-1000 mg in 40 days. Adenovirus was administered to the mice systemically via tail vein injection. The mice were treated systemically 24 h prior to adenovirus administration with 0.2 ml clodronated liposomes to suppress the removal of adenovirus by Kupffer cells in the liver. In a LOX IMVI melanoma xenograft model system a similar clodronated liposome treatment of athymic mice resulted in a greater than 10-fold increase in the adenovirus transgene expression in the treated xenografts compared to untreated ones. The mice with adrenal xenografts were injected with 5E10 viral particles of the adrenal-specific adenovirus. Semi-quantitative RT-PCR analysis of mRNA isolated from the xenografts 24 h following adenovirus administration showed expression of the thymidine kinase viral transgene with xenografts from animals treated with clodronated liposomes showing higher expression. These results indicate that the cells in the NCI-H295R xenografts maintained sufficient adrenal characteristics to activate the adrenal-specific promoter nucleotide sequences that direct thymidine kinase synthesis. This adrenal-specific adenoviral gene therapy construct provides a new approach to targeting adrenal cancer cells relative to normal liver. While this adrenal xenograft model system is useful to test our adenoviral vector, it should also be useful for the analysis of other therapies for adrenal cortical cancer.
Abstract 14816: Competing Risk of Myocardial Infarction vs Stroke in the Elderly Treated for Hypertension: A Meta-analysis of Randomized Trials
Authors: Georges El-Hayek, Sripal Bangalore, Saurav Chatterjee, Abel Casso Dominguez, Patricia Chavez, Eyal Herzog, Alexandre Benjo, Franz Messerli
Journal: Circulation (2014)

Background: Several trials have reported beneficial effects of systolic blood pressure (SBP) control in the elderly in reducing cerebrovascular events. However, concerns regarding a possible J-curve relationship between diastolic blood pressure (DBP) lowering and incident myocardial infarction (MI) warrant against aggressive DBP lowering. Therefore, it remains unclear if the risks of MI outweigh those of stroke at the BP achieved and whether more aggressive BP control is safe.

Methods: We searched PubMed and Scopus databases from inception until May 2014 for randomized controlled trials (RCTs) in which elderly patients (>65 years) were randomized to different antihypertensive treatments or to placebo and achieved different levels of BP control. A comparative estimate was made for the combined rates of MI and stroke in the framework of a meta-analysis and expressed as risk ratios (RRs) and 95% confidence intervals.

Results: We included 49,296 patients from 13 RCTs. In the overall population, the rates of stroke (4.6%) were significantly higher than the rates of MI (2.9%) (RR: 2.01, 95% CI, 1.64 to 2.45; p< 0.00001). In the less aggressive management group, the range of BP achieved was 142-178/72-97 mmHg and the risk of stroke exceeded the risk of MI (RR: 2.71, 95% CI, 1.77 to 4.14; p<0.0001). Similar results were found in the group treated more aggressively with achieved BP range of 136-159/68-85 mmHg (RR: 1.70, 95% CI, 1.36 to 2.12; p<0.00001).

Conclusion: Regardless of the BP level achieved, the risk of stroke far outweighed the risk of MI in the elderly treated for hypertension suggesting need for more specific and/or aggressive antihypertensive therapy.

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Randomized phase II trial of melanoma peptides with Montanide ISA 51 and different doses of IL-12 with Alum for resected stages IIC/III and IV melanoma
Authors: J. S. Weber, J. Snively, S. Sian, J. Delto, S. Groshen, C. Gee, R. Scotland
Journal: Journal of Clinical Oncology (2005)

2506 Background: Based on a prior study (Lee et al, J Clin Oncol 19: 3836 2001), we attempted to augment immune responses to defined melanoma antigens with IL-12 and/or GM-CSF added to a multi-peptide vaccine. Methods: Sixty patients with high-risk resected stages IIC/III and IV melanoma in an ongoing study were randomly allocated to receive melanoma peptides gp100 209–217 (210M), MART-1 26–35 (27L), and tyrosinase 368–376 (370D) with adjuvant Montanide ISA 51 and either: IL-12 at 30 ng/kg, with alum, (group A) IL-12 at 100 ng/kg with alum (group B), or IL-12 at 30 ng/kg with 250 mcg of GM-CSF (group C). Vaccinations were given subcutaneously every other week four times, then every four weeks three times, then eight weeks later, then again six months later for nine total injections. Results: Median age was 50, with 35 males and 25 females; 3 patients had stage IIC, 49 stage III and 8 stage IV melanoma. One patient had grade III colitis and discontinued therapy with resolution of symptoms; one patient had grade III headache that resolved after stopping IL-12 but continued the peptides. All other toxicities were grades I/II and resolved rapidly. Forty-four patients are evaluable so far for immune response by ELISPOT assays of fresh peripheral blood cells. A higher rate of immune response to gp100 and MART-1 was observed in group B (14/15) versus groups A (8/16) or group C (1/13) (p=0.005 for gp100 and 0.02 for MART-1). The mean amplitude of response to gp100 and MART-1 was also higher in group B (for gp100, 131 spots per 105 post- vs. 10 spots pre-vaccine) compared with groups A (60 vs. 6 spots) or C (16 vs. 11 spots). With a median of 13 months of follow-up, 5 patients of 60 have died, four in the low dose IL-12 groups, and one in the high dose IL-12 group. Sixteen patients have relapsed; 12 in the low dose IL-12 groups, and only 4 in the high dose IL-12 group. Immune responses to gp100 and MART-1 heteroclitic and wild-type peptides were similar and were also maintained at the 12 month boost. Conclusions: Higher doses of IL-12 are well-tolerated, are effective vaccine adjuvants, and augment an immune response to melanoma antigens that might correlate with clinical benefit. No significant financial relationships to disclose.
Socioeconomic and geographic disparities in immediate reconstruction after mastectomy in the United States.
Authors: Barbara A. Wexelman, Xiangji Ma, Alison Estabrook, Ayemoethu Ma
Journal: Journal of Clinical Oncology (2012)

63 Background: Disparities are found in breast cancer diagnosis, treatment, and outcomes. We seek to determine if socioeconomic and geographic disparities exist nationally in immediate reconstruction type after mastectomy. Methods: This retrospective study compares socioeconomic and geographic features for 14,986 women who underwent mastectomy in 2008 using the Nationwide Inpatient Sample (NIS), an all-payer stratified statistical sample of all US hospital discharges. Statistical analysis was performed to understand variations between three groups: patients without reconstruction (NR), patients who underwent breast implant/ tissue expander reconstruction (TE), and patients with advanced reconstruction techniques such as free or pedicled flaps (FLAP). Results: The majority of women (63%) had no reconstruction (NR), while 25.3% had TE and 12% underwent FLAP. Compared to patients with NR, women with TE or FLAP were younger (64.9 years vs. 51.3 &amp; 51.1 years, p&lt;0.001), had fewer chronic conditions (3.85 NR vs. 2.60 TE &amp; 2.54 FLAP conditions, p&lt;0.001), and higher mean hospital charges ($22,300 NR vs. $42,850 TE and $48.680 FLAP, p&lt;0.001). The length of stay was longest for FLAP patients (3.62 days) compared to the NR group (2.02 days) and the TE group (1.90 days), p&lt;0.001. Caucasians were disproportionately more likely to undergo both TE and FLAP compared to Black and Hispanic women. Patients with FLAP reconstruction were more likely to have private insurance (81.1%), than TE (80.1%) and NR (35.2%) while women without reconstruction were more likely to have Medicare and Medicaid insurance. Compared to NR, those undergoing reconstructions were more likely to live in zip codes with higher average incomes and more likely to live in or near a major city (&gt;1 million people). The states with the highest rates of FLAP reconstruction are New Hampshire (52.9%), Kansas (22.6%), New York (20.9%), and New Jersey (20.0%). Conclusions: This is the first national study analyzing patients of all insurance types and regions of the US to show statistically significant disparities in the type of immediate reconstruction after mastectomy based on age, race, insurance type, and geographic location.
CPT11/FA/5-FU versus ELF in chemonaive patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: A randomized phase II study
Authors: M. H. Moehler, J. Siebler, T. Hoehler, J. Janssen, A. Wein, M. Menges, D. Flieger, T. Junginger, P. R. Galle, M. Heike
Journal: Journal of Clinical Oncology (2004)

4064 Background: Combinations of irinotecan (CPT11) with continuous folinic acid (FA) and 5-fluorouracil (5-FU) have shown promising activity in advanced or metastatic gastric cancer (AGC). We prospectively evaluated toxicity, efficacy and survival of CPT11/FA/5-FU (arm A) versus Etoposide/FA/5-FU (ELF; arm B) in AGC. As ELF was not inferior to FAMTX or Cisplatin/5-FU in a recent EORTC trial, ELF served as control arm. Methods: Metastatic or locally advanced adenocarcinoma of the stomach or gastroesophageal junction; performance status (PS) 0–2; no prior chemotherapy. Patients (pts) were eligible and randomized to arm A with CPT11 80 mg/m2, FA 500 mg/m2, 24h-5-FU 2000 mg/m2, d 1,8,15,22,29,36, q7w or to arm B with E 120 mg/m2, FA 300 mg/m2, 5-FU 500 mg/m2, d1–3+22–24, q6w. Results: From Nov 2000 to Apr 2003, (A/B) 56/58 pts were randomized. Median age (61/63 y), gender, distribution of tumors of gastric origin and esophageal junction, rate of surgical pretreatment (52/53%), PS, localization and numbers of metastatic sites were comparable for both arms. Median treatment duration were 14.1 (0.1–90) and 6.4 (0.3–61) weeks. All pts were eligible and evaluable for toxicity, 48/52 pts for response in A/B, respectively. Grade 3/4 toxicity per pt for A/B (%): neutropenia 7/47, neutropenic fever 7/7, diarrhoea 20/0, nausea 16/7, emesis 7/5, asthenia 2/7, 1 death occurred in A due to pt incompliance after 5 days diarrhoea, 2 deaths due to cerebrovascular events in B. Best overall response (% of pts) for A/B: CR 4/0, PR 40/17, NC 14/12, tumor control rate (CR+PR+NC) 58/29. Median progression-free time for A/B: 129 (CI95% 8–693) and 63 (0–545) days. Overall survival has not yet been reached. Conclusions: CPT11/FA/5-FU is highly effective in advanced or metastatic gastric cancer. CPT11/FA/5-FU can safely be given on an outpatient basis with proper management of adverse events. Cardiovascular deaths occurred only with ELF. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Germany
Effect of co-morbidity burden on survival following salvage re-irradiation for patients with recurrent or second primary squamous cell carcinoma of the head and neck
Authors: T. Tanvetyanon, T. Padhya, J. McCaffrey, D. Boulware, R. C. DeConti, T. McCaffrey, M. El-Deiry, A. Trotti
Journal: Journal of Clinical Oncology (2008)

6051 Background: Salvage re-irradiation (ReRT) is a treatment option for squamous cell carcinoma of the head and neck (SCHN) that recurs in a previously irradiated area. ReRT, though toxic, can produce long-term survival, even when tumor is unresectable or poor prognostic feature is present after salvage surgery. The degree to which patient co-morbidities serve as a predictor of survival following re-RT has not been studied to date. Methods: Patients (pts) with SCHN who underwent ReRT with an overlapping target to previous RT during 1998–2007 at our institution were eligible. Co-morbidity burden was assessed by Charlson Index (CI), measuring frequency of co- morbid diseases as score 2–27, and Adult Comorbidity Evaluation-27 (ACE-27), measuring frequency & severity of co-morbid diseases as score 0–3. Results: 69 total pts, including 25 who had salvage surgery, had a median age of 62 yrs. Most common site was oropharynx (48%). Median time since previous RT was 35 mos. Of 41 pts with measurable disease, median tumor bulk was 3 cms. ReRT was delivered at a median of 60 Gy. IMRT/3-D RT was used in 51%; Concurrent chemotherapy, in 78%. Median survival (MS) was 18.3 mos (95% CI 14–30); PFS 13.4 mos. Comorbidity burden by CI showed that 58% of pts had a score >2 (i.e. had ≥1 comorbid disease other than the current cancer). By ACE-27, 20% of pts had a score of 2 or 3 (mod or severe decompensation). Higher co-morbidity scores predicted worse survival. By CI, MS was 30 mos if score ≤2 vs. 14 mos if score >2 (p=0.003). By ACE-27, MS was 19 mos if score 0–1 vs. 12 mos if score 2 or 3 (p=0.004). Using Cox model, this remained significant after adjusting for ReRT dose and tumor bulk, which were also survival predictors (p=0.007, 0.001). Time from previous RT, new primary, IMRT/3-D RT, or salvage surgery were not significant predictors. Grade ≥3 toxicities were 36% at baseline & 68% at follow-ups (dysphagia most common). Late toxicities including trismus, fistula, and soft tissue necrosis occurred in 7, 2, and 4 pts. Conclusions: Co-morbidity burden is a strong, independent predictor of survival among selected pts undergoing salvage ReRT. This information, along with other prognostic factors, may help refine patient selection and improve future treatment outcome. No significant financial relationships to disclose.