tbuckley/cabot-search huggingface dataset:
Analysis of the relationship between Karnofsky performance status (KPS) and tumor response in the RECORD-1 phase III trial of everolimus in patients with advanced renal cell carcinoma (RCC).
Authors: C. Porta, B. Escudier, T. E. Hutson, R. A. Figlin, E. Calvo, V. Grünwald, S. Osanto, A. Ravaud, A. Panneerselvam, J. J. Knox, R. J. Motzer
Journal: Journal of Clinical Oncology (2011)

4610 Background: In the RECORD-1 phase III trial of patients with metastatic RCC who failed initial sunitinib or sorafenib, everolimus reduced tumor burden in 47% of patients (vs 10% on placebo). Notably, everolimus also prolonged the time to KPS deterioration (≥10%) (5.78 vs 3.84 months). This retrospective analysis of RECORD-1 further explores the relationship between KPS deterioration and response (as measured by best percent change in tumor size, best overall response, and progression-free survival [PFS]). Methods: Eligible patients had baseline KPS ≥70% and measurable mRCC that progressed on initial sunitinib or sorafenib. Patients received everolimus 10 mg/day (n = 277) or placebo (n = 139) plus best supportive care. Tumor response was assessed centrally according to RECIST. KPS was determined at baseline, day 1 of each 28-day cycle, and end of study treatment. Results: Mean baseline KPS for all patients was 88%. At study end, everolimus-treated patients showed less deterioration in KPS than placebo-treated patients (mean ΔKPS = −8.08 vs −13.09; P = 0.025). Patients in either arm who achieved a partial response (PR, n = 5) or stable disease (SD, n = 229) had less deterioration of KPS than patients with progressive disease (PD, n = 131): mean ΔKPS = −2.00, −7.03, −14.50, respectively; P = 0.002 for SD vs PD. In everolimus-treated patients, however, the change in KPS was not correlated with best percent change in tumor size (Pearson correlation coefficient, 0.050; P = 0.489), suggesting that even patients with minimal or no reduction in tumor burden may derive KPS benefit from everolimus. In the subgroup of patients with no deterioration in KPS at the end of study treatment (ΔKPS ≥0), everolimus significantly prolonged PFS vs placebo (4.90 vs 3.48 months, HR = 0.44, P < 0.001). Conclusions: In RECORD-1, everolimus delayed and reduced the degree of KPS deterioration versus placebo. Furthermore, in patients with stable KPS, everolimus was associated with improved PFS over placebo. These results provide further evidence of the efficacy and tolerability of everolimus in patients with mRCC who fail initial sunitinib or sorafenib.
Induction and concurrent chemoradiotherapy with cetuximab for patients with locally advanced nasopharyngeal carcinoma.
Authors: G. F. Ho
Journal: Journal of Clinical Oncology (2011)

e16031 Background: EGFR receptors are overexpressed in 80% of nasopharyngeal carcinoma (NPC) and have been associated with more advanced tumors at presentation. Inhibition of EGFR on NPC xenograft suppresses tumor growth as well as potentiates the chemotherapy effect. Addition of cetuximab to chemotherapy may increase the cure rate of locally advanced NPC. Methods: Patients with histologically confirmed, newly diagnosed locally advanced (UICC/AJCC stage III to IVB) nasopharyngeal carcinoma were treated with 2 cycles of induction chemotherapy with cisplatin 75 mg/m2 D1, 5FU 1000 mg/m2/day D2-5, and weekly cetuximab (400 mg/m2 initial dose, then 250 mg/m2 weekly), followed by 7 weekly doses of cisplatin (30 mg/m2) and cetuximab (250 mg/m2), concurrent with radiation. Radiotherapy was delivered using conformal technique to total dose of 70Gy in 35 daily fractions for 7 weeks. Primary endpoints were safety and feasibility. Study was approved by local medical ethics committee. Results: 20 patients were targeted in this phase 2 study, but the trial was halted after recruitment of 3 patients due to safety concern. First patient developed pancytopenia and recurrent bacterial infections after 2 cycles of induction chemotherapy with cetuximab, and failed to complete the radiation treatment, eventually died of neutropenic sepsis. Second patient completed induction and concurrent chemoradiotherapy and was well after 6 month follow up. The third patient completed planned treatment on schedule but had grade 4 skin toxicity and died of unknown cause at home a month of completing therapy. The study was halted by the medical ethics committee due to these significant complications. Conclusions: Induction and concurrent chemotherapy with cetuximab and conformal radiotherapy remains an unproven strategy and carries potential significant risks. Intensity modulated radiotherapy technique may be required due to a potential cord sensitisation effect of the conrrent regimes with the conventional technique.
Prognostic significance of double-stranded RNA-activated protein kinase (PKR) expression in small-size peripheral adenocarcinoma of the lung
Authors: M. S. Roh, H.-C. Kwon, T. H. Hwang, P. J. Choi, S.-H. Cho
Journal: Journal of Clinical Oncology (2005)

7281 Background: We investigated the protein expression of double-stranded RNA-activated protein kinase (PKR), which was identified by using a previous cDNA microarray study. We wanted to discover PKR’s correlations with several pathologic parameters, and we also wanted to elucidate its role in neoplastic transformation and progression of lung adenocarcinomas. Methods: Immunohistochemistry for PKR was performed and a semiquantitative scoring method was calculated based on staining intensity and percentage of immunoreactive tumor cells (high vs. low) for investigating one bronchioloalveolar carcinoma (BAC), 16 adenocarcinomas consisting of BAC and invasive carcinoma (mixed) and 21 invasive adenocarcinomas without BAC (invasive). Results: The BAC showed high-grade expression (100%) and the mixed type tended to more frequently show high-grade expression (56.3%) than the invasive type (14.3%) (P = 0.028). There were no significant associations with age, tumor size, lymph node metastasis, lymphovascular invasion or the pathologic stage. The Kaplan-Meier survival curves demonstrated that the patients with high-grade PKR expression had significantly shorter survival periods than those patients with low-grade PKR expression (P = 0.018). Conclusions: These results do not support the concept of PKR as a tumor suppressor, but instead they indicate that PKR overexpression might be associated with a much earlier step in carcinogenesis. This might imply an important role for PKR for cancer progression in small-size peripheral adenocarcinomas of the lung. No significant financial relationships to disclose.
Biomarker distribution and characteristics for the first 100 patients in MAVERICC, a randomized phase II study of mFOLFOX6-bevacizumab (BV) versus FOLFIRI-BV in previously untreated metastatic colorectal cancer (mCRC).
Authors: Alexander Starodub, Sachdev P. Thomas, Fa-Chyi Lee, Vallathucherry Harish, Han A. Koh, Edith P. Mitchell, Romeo Ang Mandanas, Sang Y. Huh, Suprith Badarinath, Angelique Mittan, Larry Leon, Tobias Vogt, Christiane Langer, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2013)

483^ Background: Retrospective analyses have suggested that ERCC1 is a chemo-resistance marker to platinum compounds; a median tumoral ERCC1 level of 1.7 × 10 –3 ERCC1/β-actin mRNA has been reported in metastatic colon cancer (Grimminger et al, Pharmacogenomics J, 2011). MAVERICC is the first prospective study of tumoral ERCC1and plasma VEGF-A as potential biomarkers for oxaliplatin- and BV-containing regimens, respectively. We present data from a planned interim biomarker distribution assessment of the first 100 patients (pts) in MAVERICC. Methods: In this randomized, open-label, phase II study, pts (N=360) with histologically or cytologically confirmed CRC and ≥1 measurable metastatic lesion are stratified at screening by tumoral ERCC1 mRNA expression (low vs high, cutoff of ≤ vs &gt;1.7). Stratified pts are randomized 1:1 to mFOLFOX6-BV or FOLFIRI-BV administered in 2-week cycles. The primary objectives are: 1) to assess ERCC1 and VEGF-A as biomarkers of progression-free survival (PFS) for oxaliplatin- and BV-containing 1st-line regimens, and 2) within ERCC1 high pts, to test whether FOLFIRI-BV is associated with a prolonged 1st-line PFS vs mFOLFOX6-BV. Results: With a data cutoff of June 19 2012, 100 pts have been enrolled. Of these, 75 pts were stratified to the ERCC1 high group and 25 pts to the ERCC1 low group. The median ERCC1 mRNA expression was 3.00 (range, 1.73–13.16) and 1.32 (range, 0.70–1.70) in the ERCC1 high and low stratification groups, respectively. Among all pts, the median ERCC1 mRNA expression was 2.37. Pt demographics by group are shown (Table). Plasma VEGF-A evaluation is ongoing. Conclusions: An analysis of the first 100 pts in MAVERICC showed that the median tumoral ERCC1 expression level was higher than the predefined cutoff, providing an adequate population of ERCC1 high pts to assess PFS by treatment regimen. Clinical trial information: NCT01374425. [Table: see text]
Prediction of the therapeutic response in colorectal cancer patients using the Spheroid Microtumor Technology
Authors: M. Joka, V. Heinemann, R. Issels, K. Jauch, B. Mayer
Journal: Journal of Clinical Oncology (2008)

22178 Background: Colorectal cancer (CRC) is the third most common malignancy and the fourth most frequent cause of cancer death worldwide. Despite significant advances in conventional therapeutic approaches, the five-year overall survival rate of CRC patients with an intended curative resection (R0) is less than 50%. Therefore, the development of a relevant preclinical drug testing model is essential to identify novel therapeutic strategies. Methods: The Spheroid Microtumor Model was established using primary tumor tissue samples from CRC patients. The spheroids were treated in vitro with both standard cytostatic drugs and molecular therapeutics, e.g. 5-FU, oxaliplatin and Cetuximab. The predictivity of the Spheroid Microtumor Model used in drug testing for the clinical situation is currently validated in a monocenter cohort study in the surgical clinic-Großhadern. Thus, using log rank statistics with a power of 80% and a type I error of 5%, 58 patients with a CRC stage II (high risk) and stage III will be randomized through a period of 24 months. An interim analysis will be done after 11 patients failing standard therapy. Results: The Spheroid Microtumor Model closely mimics the tumor biology of microtumors in cancer patients, i.e. tumor differentiation, low tumor cell proliferation, tumor heterogeneity, interaction with stromal cells and drug resistance. Therefore, this test system allows the selection of the most therapeutically relevant drug candidates, i.e. cytostatics, antibodies and small molecules in different concentrations, combinations and sequences. We have shown the loss, changes and mutations of the most prominent indicators for 5-FU sensitivity, i.e. thymidylate synthase, thymidine phosphorylase and a higher activation of the dihydropyrimidine dehydrogenase in a variety of CRC tumors. Conspicuously, target proteins have been upregulated, such as EpCAM, CEA, MUC-1, EGF-R and CD44v6. Conclusions: The Spheroid Microtumor Model represents a valid test system for ex vivo testing of conventional and molecular therapeutic strategies for the clinical situation. The combination of molecular target profiling and functional drug testing is a prerequisite for individualized cancer therapy. No significant financial relationships to disclose.
Toxicity symptom reporting by patients and clinicians during phase III trial comparing androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in hormone-naïve metastatic prostate cancer (GETUG-AFU 15/0403).
Authors: G. Gravis, K. Fizazi, B. Esterni, C. Protiere, M. Habibian, M. Soulie, I. Latorzeff, F. Priou, F. Joly, S. Oudard
Journal: Journal of Clinical Oncology (2010)

6155 Background: During chemotherapy or trials it is common practice for clinicians to report toxicities using standard criteria. Our aim was to compare this evaluation to patients (pts) self reporting symptoms, in the context of a phase III trial with docetaxel (D) in hormone-naive metastatic prostate cancer (HNMPC) pts. Methods: Pts with HNMPC were randomly assigned to arm A (ADT plus D: 75mg/m2/q3w, 9 cycles) or arm B (ADT alone). Clinician (common toxicity criteria (NCICTC V3.0) and patient symptom self-assessment (specific questionnaire) were reported at 3 months of treatment. Data were collected for 17 symptoms. Results: From 10/2004 to 12/2008, 385 pts were accrued. Participation rates in pts self assessment was 58% with 95% compliance rates in completion questionnaire. Clinicians reported assessment was 90%. As a mean for the 17 side effects (SE) assessed in both arms, patients declared 35% of SE, while clinicians declared only 8,4% (27% differences mean). Whole SE where more frequently reported by patients than by physicians. The subjective SE for which the patients are the only source of information (fatigue, hot flushes etc) the difference mean is much higher (30%) than for objective SE (21%). Interestingly two SE exhibit a specific reporting pattern between patients vs physicians: hot flushes for which the difference for physicians is 17% vs. 55% for patients in arm A (p < 0.0001) and 72% vs. 79% in arm B (p = 0.26). Nail loss (only observed in arm A) was evaluated respectively by physicians and pts at 3 months: 1.1% and 3.7% (p = 0.21) and at 6 months 33% vs. 25% by pts: 25%, no differences. From this observation, it was apparent that physicians under-evaluate the frequency of SE except specific toxicity like nail loss. Conclusions: Pts provided information which was captured less frequently by the physicians. Due to high variability/difference between patients and physicians assessment of side effects, the process of drug validation/authorization could be improved if the data about patients self evaluation is also integrated. No significant financial relationships to disclose.
Risk factor assessment of hospice patients who are readmitted within 7 days of acute care hospital discharge.
Authors: Anthony E Wilson, Diana Martins-Welch, Bridget Earle, Andrzej Kozikowski, Lori Attivissimo, Lisa M Rosen, Renee Pekmezaris
Journal: Journal of Clinical Oncology (2015)

121 Background: Although 20% of adults 65 and older are re-hospitalized within 30 days of discharge, there is a dearth of research investigating readmission of patients discharged to hospice and the predictors of the readmissions. The study aim was to identify risk factors for hospital readmission within 7 days of discharge to home hospice. Methods: This was a retrospective case control study with cases being patients discharged to home hospice that were readmitted to the hospital within 7 days. Controls were patients discharged to home hospice and not readmitted to the hospital within 7 days. Descriptive statistics were used to describe demographic and clinical characteristics. The chi-square or Fisher’s Exact test were used to compare categorical predictors between cases and controls. The two-sample t-test or the Mann-Whitney test were used to compare continuous predictors between cases and controls. Results: There were 163 subjects; 46 cases (28.22%) and 117 controls (71.78%). The most frequent hospital diagnosis was cancer (56.4%). There was a significant association between 7-day readmission (i.e., case) and age (P &lt; 0.0041), race (P &lt; 0.0008), language (P &lt; 0.0007) and insurance (P &lt; 0.0001). Specifically, cases were significantly younger than controls (69.5 vs. 77.0). Cases were more likely to be Hispanic (15.2 vs. 5.1), Asian (15.2 vs. 5.1) and other (13.0 vs. 2.6) when compared to controls. Cases were more likely to speak Spanish (13.3 vs. 3.5) or other (20.0 vs. 5.3) and less likely to speak English (66.7 vs. 91.2). Cases were less likely to have Medicare (8.7 vs. 82.9) and more likely to have Medicaid (32.6 vs. 4.3), private insurance (13.0 vs. 10.3) or other form of insurance including dual eligibility (45.7 vs. 2.6). Gender, marital status, religion, hospital diagnosis, discharge day, family support at home, symptoms and emergency contact relationship were not significantly association with 7-day readmission. Conclusions: Our data highlights four risk factors, namely age, race, language and insurance status as factors predicting readmission within seven days of acute care hospital discharge. Further study of these predictors may identify opportunities for interventions to obviate these readmissions.
Disparities in the availability of and access to antiemetics recommended by the international antiemetic guidelines in Serbia, Japan, and Nepal.
Authors: Snezana Bosnjak, Ana Zilic, Bishal Gyawali
Journal: Journal of Clinical Oncology (2016)

117 Background: Guideline-consistent antiemetic therapy requires 4 classes of antiemetics (AEs) to be available and accessible for the optimal prevention of chemotherapy induced nausea and vomiting (CINV): serotonin3 receptor antagonists (5HT3RAs), neurokinin 1 receptor antagonists (NK1RAs), dopamine receptor antagonists (DOPRAs) and dexamethasone. To evaluate disparities in the availability and accessibility of AEs recommended by the international antiemetic guidelines for the prevention of CINV inpatients treated in governmental hospitals in Nepal (low), Serbia (upper-middle) and Japan (high-income). Methods: Availability was evaluated by the formulary availability and marketing authorization (MA) in Serbia (RS), Japan (JP) and Nepal (NP). Accessibility was assessed by the National Health Insurance Fund (NHIF) coverage in Serbia and Japan and by the affordability in Nepal. Off-label use of medications is not legitimate in Serbia and Japan. Results: Barriers are presented in Table. Serbia has no access to NK1RAs and palonosetron for the prevention of CINV after HEC-AC and carboplatin. There are no barriers in Japan to provide all 4 classes of AEs. In Nepal all AEs are payed out of pocket and the guideline implementation completely depends on the affordability. Olanzapine is accessible in Nepal, but not in Japan and Serbia due to restricted off-label use of medications. Conclusions: The real life implementation of antiemetic guidelines for the prevention of CINV in various countries depends on the availability of and access to AEs recommended by the guideline. Identified barriers in Serbia and Nepal preclude physicians from providing optimal supportive care. [Table: see text]
Exploratory study of monoterpene perillyl alcohol intranasal administration in patients with recurrent gliomas
Authors: C. O. Da Fonseca, T. Q. Santos, D. Futuro
Journal: Journal of Clinical Oncology (2008)

14650 Background: This work discusses intranasal delivery of perillyl alcohol (POH) as a potential therapeutic strategy for patients with relapsing malignant gliomas. The proposed mechanism of action involves inhibition of post-translational isoprenylation of p21-Ras. Deregulated p21-Ras function, contributes to growth of malignant gliomas. Intranasal delivery is a practical and non-invasive approach that allows therapeutic agents which do not cross the blood-brain barrier to enter the Central Nervous System, reducing unwanted systemic side effects. Patients and Methods: Applying this method we performed a phase I/II study of POH in patients with relapsed malignant gliomas after standard treatment. POH was administrated in concentration 0.3% volume/volume (55mg) 4 times daily. The objective of this study was to evaluate the toxicity and progression-free survival after 6 months of treatment. The cohort consisted of thirty-seven patients including 29 with GBM, 5 with AA and 3 with AO. Neurological examination and suitable image analysis (MRI) established disease progression. Complete Response was defined as neurological stability or improvement conditions, disappearance of MRI tumor image and corticosteroid withdraw; Partial Response defined as ≥ 50% reduction of MRI tumor image, neurological stability or improvement conditions and corticosteroid requirement; Progressive Course was defined as ≥ 25% increase MRI tumor image or appearance of a new lesion; Stable Disease was defined as lack of any changes in the MRI tumor image or neurological status. Results: After 6 months of treatment it was observed: Partial Response: 3.4% (n=1) with GBM and 33,3% (n=1) with AO; Stable Disease: 44.8% (n=13) with GBM, 60% (n=3) with AA and 33.3% (n=1) with AO; Progressive Course: 51.7% (n= 15) with GBM, 40% (n=2) with AA and 33.3% (n=1) AO. The progression free survival was 48.2% for patients with GBM, 60%, 66.6% for AA patients and 66.6% for AO patients. Conclusion: The present work indicates that POH intranasal administration is a safe, non invasive, low cost and regression of tumor size in some patients is suggestive of antitumor activity. No significant financial relationships to disclose.
Octreotide prescribing patterns in the palliation of symptomatic inoperable malignant bowel obstruction patients at a single U.S. academic hospital.
Authors: Eric Roeland, Michael Hwang
Journal: Journal of Clinical Oncology (2013)

563 Background: Medical management is the cornerstone of malignant bowel obstruction (MBO) therapy and includes antisecretory agents such as octreotide. Currently, little data exist regarding octreotide prescribing patterns in U.S. academic hospitals in the palliation of inoperable MBO. Methods: This retrospective chart review evaluated inpatient with inoperable MBO receiving octretodie at a single academic US hospital (2008-2011). The prescribing primary service (medical vs. surgical), days to initiation of octreotide, daily dose, cumulative dose, length of stay (LOS), and overall survival (OS) were analyzed. Multiple linear regression was used to assess if the association between dose and LOS was significant. Kaplan-Meier curves and log rank test were used to evaluate OS. Results: A total of 767 patients received octreotide. 134 had diagnosis of cancer, and 37 (24 female, 13 male; mean age 56.7 years) had a confirmed inoperable MBO. The mean LOS was equivalent on both services (17 days). The mean octreotide dose was 201.2-μg medical vs. 119-μg surgical. Mean time to initiation was 8.4 days (7.9 medical vs. 8.8 surgical). Earlier initiation was associated with a shorter LOS (Spearman’s correlation= 0.76, p&lt;0.0001). No statistically significant association was demonstrated between OS octreotide dose. Conclusions: Early initiation of octreotide may lead to shorter LOS; the association remains after adjustment for patient age. Timing and dose of octreotide use was not significantly associated with survival.