tbuckley/cabot-search huggingface dataset:
Survival with cetuximab/FOLFOX or cetuximab/FOLFIRI of patients with nonresectable colorectal liver metastases in the CELIM study.
Authors: Gunnar Folprecht, Thomas Gruenberger, Wolf Bechstein, Florian Lordick, Hauke Lang, Jürgen Weitz, Thomas Suedhoff, Joerg Thomas Hartmann, Torsten Liersch, Claus-Henning Kohne
Journal: Journal of Clinical Oncology (2012)

540 Background: Non-resectable liver metastases (mets) can be resected if they responded to systemic treatment. Cetuximab increases response rates in patients with k-ras wild type (wt) tumours. Methods: Patients (pts) with non-resectable liver mets (defined as technically non-resectable or ≥ 5 liver mets) were randomized to cetuximab/FOLFOX (arm A) or cetuximab/FOLFIRI (arm B). Resectability was re-evaluated after four and then every 2 months. Resection was offered to pts who became resectable during treatment. (Folprecht et al, Lancet Oncol 2010) Progression free survival (PFS) and overall survival (OS) were analysed in June 2011. Results: One hundred nine pts were randomized to cetuximab/FOLFOX or cetuximab/FOLFIRI, 106 evaluable for response. The median OS in all pts was 33.1 months [95% CI: 25.8-40.4], 35.7 [29.9-41.6] mo. in arm A and 29.0 [18.1-39.8] mo. in arm B (HR 1.09 [0.69-1.72]). The 4-year OS was 28% in all pts. The PFS was 11.2 [7.2-15.3] and 10.5 [8.9-12.2] mo. in arm A and B, respectively (HR 1.15 [0.77-1.70]). According to the k-ras mutational status, the OS and PFS was 36.1 [24.4-47.8] and 11.9 [8.25-15.6] in k-ras wt, 27.4 [15.7-39.1] and 9.9 [4.5-15.2] in k-ras mutant pts. In the k-ras wt subset, the OS was 35.8 [30.2-41.4] and 41.6 [24.8-58.5] mo. in arm A and B (HR 1.01 [0.55-1.86]), the PFS 12.1 [5.2-19.1] and 11.5 [8.8-14.1] mo. in arm A and B (HR 1.09 [0.66-1.79]). Pts with R0 resection had a significantly longer OS (median 46.7 [30.7-62.7] mo.) than pts without (median OS: 27.3 [21.2-33.3] mo, p=0.002). In R0 resected pts, the 3- and 4 year OS was 64% and 49%. The median disease free survival (DFS) was 9.9 mo after R0 resection, the 2 year DFS 19%. According to a review of CT/MRI scans which was performed by surgeons blinded to all clinical data, there was no survival difference between “resectable” pts and pts not categorized as “resectable” at baseline (HR 0.81 [0.44-1.50]), but a significantly better OS was observed for pts regarded as “resectable” after treatment vs. other categories (HR 0.47 [0.27-0.83], p=0.007). Conclusions: Pts had a favourable overall survival which was longer in R0 resected pts. Resectability after treatment seems to be important for the pts outcome.
Assessement of the pathogenic role of <i>MSH2</i> missense variants in HNPCC syndrome
Authors: L. Belvederesi, F. Bianchi, E. Galizia, R. Catalani, R. Bracci, C. Loretelli, M. Amati, R. Cellerino
Journal: Journal of Clinical Oncology (2008)

22154 Background: Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is associated with inherited defects in genes involved in postreplicative DNA MisMatch Repair (MMR), mainly MLH1 and MSH2. A significant proportion (20–25%) of the reported variants consists of missense mutations: a single amino acid change with uncertain pathogenetic significance. Up to date a validated test, able to clarify the role of MSH2 missense mutations, is not available. This arouses uncertainty regarding clinical surveillance for patients and families carrying MSH2 missense variants. We analysed 3 non-truncating MSH2 mutations (G162R D167H R359S), found in clinically suspected HNPCC families, in order to assess in a human expression system their ability to correctly localize into the nucleus. Methods: Clinical data were correlated with nature of AA change, MSI (Micro Satellite Instability) and IHC (ImmunoHystoChemistry). Localization assay: the 3 missense variants were cloned into the pEGFP-N1 eucariotic expression vector in frame with the EGFP (Enhanced Green Fluorescent Protein) encoding gene. Wild type and a pathogenetic variant were used as controls. Subcellular localization of controls and mutated MSH2-EGFP fusion proteins was analysed in the human 293 MMR proficient cell line by direct fluorescence microscopy. Results: See Table. Conclusions: Localization analysis seems to be of aid in order to establish a pathogenetic role of MSH2 missense mutations and could represent a useful tool in clinical practice and in genetic counselling. Age/sex Family history AA change Nature AA change MSI IHC MSH2 IHC MLH1 Localization Pathogenetic 55/F Bethesda G162R nonpolar→ Basic 60% − + Altered (Nucleus+ cytoplasm) Likely 42/M Bethesda D167H Acidic→ Basic ND + − Normal (Nucleus) Unlikely 59/F Amsterdam R359S Basic→ Uncharged polar 80% − + Altered (Cytoplasm) Likely No significant financial relationships to disclose.
Tremelimumab, a monoclonal antibody against CTLA-4, in combination with subtotal ablation (trans-catheter arterial chemoembolization [TACE], radiofrequency ablation [RFA] or cryoablation) in patients with hepatocellular carcinoma (HCC) and biliary tract carcinoma (BTC).
Authors: Austin G. Duffy, Oxana V. Makarova-Rusher, Drew Pratt, David E Kleiner, Suzanne Fioravanti, Melissa Walker, Stephanie Carey, William Douglas Figg, Seth M. Steinberg, Victoria Anderson, Elliot Levy, Venkatesh Krishnasamy, Bradford J. Wood, Tim F. Greten
Journal: Journal of Clinical Oncology (2016)

270 Background: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and results in inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. Transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA) and cryoablation (CA) have been shown to induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment in patients with advanced HCC. Methods: Patients with HCC [Childs Pugh A/B7; BCLC B/C; ECOG 0/1; post-sorafenib (BCLC stage C only)] or refractory BTC were enrolled in a study of Tremelimumab combined with subtotal TACE, RFA or CA performed on week 6. All BTC patients received RFA as the immune-stimulant in combination with tremelimumab. Tumor biopsies were performed at baseline and at time of RF/TACE. Results: 34 pts enrolled (28 HCC, 6 BTC). Characteristics: M:F 26:8; Median age 54(range 42-76); In HCC pts cirrhosis present in 17pts, BCLC Stage B/C: 9/19; Hepatitis B/C/neg: 4/15/9. 13 pts received TACE, 16 underwent RFA (inc 6 BTC pts), 3 CA during week 6 of tremelimumab therapy. 2 pts did not receive an ablative procedure. No DLT encountered. Most common toxicity was pruritus. One patient developed pulmonitis and was taken off study but remained disease-free at 16m. Of N = 17 pts evaluable for response outside of TACE/RFA-treated lesion 4 (23.5%) achieved confirmed partial responses. 8 of 9 pts with quantifiable HCV experienced a marked reduction in viral load. 6-week tumor biopsies showed immune cell infiltration on all evaluable patients. Median PFS for the evaluable HCC population (N = 25) was 5.7m. Conclusions: Tremelimumab in combination with subtotal TACE, RFA or CA in patients with advanced HCC and BTC is safe and feasible. Obtaining tumor biopsies at baseline and at the time of RFA/TACE is safe. Evidence of immune cell infiltration was seen on evaluable patients. Encouraging clinical activity seen with objective confirmed responses, PFS 5.7m and possibly surrogate reductions in HCV viral load. Clinical trial information: NCT01853618.
Comparative study on the protective effect of different bisphosphonates in decreasing bone mineral density in patients submitted to androgen deprivation therapy. A placebo controlled study
Authors: P. Rodrigues, F. Hering, A. Meler, Y. Afonso, A. Azoubel, J. Campaganri
Journal: Journal of Clinical Oncology (2005)

4643 Background: Androgen deprivation therapy (ADT) to treat hormone-refractory prostate cancer (HRPC) patients can promote bone demineralization. Bisphosphonates is an emerging therapy to treat this condition. We prospectively evaluated 100 randomized patients concerning 3 treatments plans after androgen ablation Methods: 97 men were enrolled in 3 arms after receiving LHRH-agonists or orchiectomy (3). 34 patients received no bone protection (control group), 39 were assigned to receive monthly I.V. clodronate (39) or monthly I.V. zoledronic acid (27). Average age was 63 years-old. The patients were followed with usual exams (PSA, serum testosterone, Plain X-ray, bone scintigraphy) and dual-energy x-ray absorptionmetry w/ densitometer every 6 months. The patients were studied in a cross-sectional study after a minimum follow-up of 36 months. Results: Patients who did not receive bone protection from bisphosphonates were more prone to bone mineral density (BMD) losses. The average time to develop osteopenia or osteoporosis after ADT for control, clodronate or zometa was 6, 24 and 18 months and 24, 28.3 and 28.5 respectively. Conclusions: Bisphosphonates has become a gold-standard to bone protection in those patients assigned to ADT in the of treatment of hormone-refractory-prostate cancer. No significant financial relationships to disclose.
Phase I study of enzastaurin (ENZ) and bevacizumab (BV) in patients with advanced cancer
Authors: L. P. Resta, S. Ermisch, C. Collins, S. J. Nicol, D. K. Armstrong, T. Wang, Z. Zhang, D. Thornton, M. A. Carducci
Journal: Journal of Clinical Oncology (2008)

3529 Background: ENZ is an oral kinase inhibitor that suppresses tumor growth through PKC and PI-3 kinase/AKT. BV is a monoclonal antibody that binds VEGF and inhibits angiogenesis. Since ENZ and BV complement each other in inhibiting angiogenesis, we conducted a Phase I study of ENZ and BV in advanced cancer patients (pts). Methods: Eligible pts had advanced cancer, adequate organ function and no co-morbidities suggesting increased risk of drug-related toxicities. Six pts were enrolled per cohort; if ≤ 1 DLT occured the next cohort opened. A treatment cycle consisted of 28 days (Dose Levels [DL] 1, 2 and 2a) or 21 days (DL 3 and 3a). A loading dose of ENZ 1125mg was given on Day 1, Cycle 1 for each cohort. DL 1 consisted of ENZ 500mg po daily and BV 5mg/kg IV on Days 1 and 15 of each cycle. Pts were then alternately assigned to DL 2 (BV 10mg/kg IV on Days 1 and 15) or DL 3 (BV 15mg/kg IV on Day 1 every 21 days). The ENZ dose remained 500mg daily. Additional pts were then alternately assigned to DL 2a (ENZ 250mg bid and BV 10mg/kg IV on Days 1 and 15) or DL 3a (ENZ 250mg bid and BV 15mg/kg IV on Day 1 every 21 days). DLT was defined as any of the following occurring in Cycle 1: Grade (G) 4 neutropenia ≥ 7 days, febrile neutropenia, G 3 thrombocytopenia with bleeding or G 4 thrombocytopenia, G 3 non-hematological toxicities, and toxicities associated with BV. Results: 24 pts (13 with ovarian cancer) are evaluable for toxicity through at least one cycle (6 each at DL 1, 2, 3 and 3 each at DL 2a and 3a). Fifteen are evaluable for response. One DLT (G 3 transaminitis) occurred after the first cycle at DL 2. This resolved after decreasing ENZ for 1 cycle, and the pt continues on study at full doses. No apparent increase in ENZ or BV toxicity was seen. One SAE (deep venous thrombosis) occurred at DL 3 after 3 cycles. Common toxicities included fatigue, chromaturia, dry/sore mouth, nausea and diarrhea. Eight pts (53%) had partial response (PR) or stable disease (SD) as best response. Seven of these pts remain on study with a range of duration of PR or SD of 8–24 weeks. Conclusions: The addition of ENZ to BV in any of the currently approved BV dosing schedules is well tolerated and clinically active in advanced cancer pts. The combination of ENZ and BV may be appropriate for further study in pts with NSCLC, colon or ovarian cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Genentech Eli Lilly
Survival and prognosticators of gastric cancer patients with only positive peritoneal lavage cytology.
Authors: Kazuki Kano, Tsutomu Sato, Yukio Maezawa, Kenki Segami, Tetsushi Nakajima, Kousuke Ikeda, Toru Aoyama, Tsutomu Hayashi, Takanobu Yamada, Takashi Oshima, Yasushi Rino, Munetaka Masuda, Takashi Ogata, Haruhiko Cho, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2016)

16 Background: Treatment strategies for only positive peritoneal lavage cytology findings have not yet been established. The objective of this retrospective study was to clarify the survival and prognosticators in these patients. Methods: Overall survival (OS) rates were examined in 39 patients with gastric cancer who underwent a curative resection and had positive peritoneal cytology in the absence of overt peritoneal metastases between January 2000 and June 2015. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model. Results: A total of 39 patients were evaluated. The median overall survival was significantly longer in the 34 patients who received chemotherapy after surgery than that in the 5 who did not (19.1 vs 5.9 months, p &lt; 0.01). Among the patients who received chemotherapy after surgery, univariate and multivariate analyses showed that pN3b was an independent significant prognosticator (hazard ratio of 4.169 with 95% CI: 1.108-15.684, p = 0.035). The median OS was 15.8 months when the patients diagnosed with N3b was 33.1 months when the patients diagnosed with N3a or lower. Conclusions: The prognosis of gastric carcinoma with positive peritoneal lavage cytology without peritoneal metastasis is still poor and need more aggressive treatment. The lymph node metastasis was a significant prognosticator in these patients.
Anorexia profile changes according to conditioning regimens in cancer patients underwent high-dose chemotherapy and stem cell transplantation.
Authors: A. Ozet
Journal: Journal of Clinical Oncology (2010)

e17006 Background: Patients that underwent high-dose chemotherapy (HDC) stem cell transplantation experience anorexia frequently. This study was done to evaluate the frequency and severity of anorexia in the early period of transplantation and the relation of conditioning regimens with anorexia. Methods: Patients with haematologic or solid tumors who underwent APSCT or ABMT were asked to score anorexia severity daily in the first 10 days after stem cell reinfusion. Scoring was performed according to a five-grade scale (0: no symptom; 1: mild; 2: moderate; 3: severe; 4: very severe). Total anorexia score (TAS) was defined as the addition of symptom severities of anorexia in 10 days. A total of 123 patients, 86 men (70%) and 37 women (30%) were included in to the study. Median age of patients was 33 (range 15-78) years. The most frequent three diagnosis were non-Hodgkin's lymphoma (29%,n=36), Hodgkin's lymphoma (25%, n = 25), and multiple myeloma (12%, n = 15). BCNU, etoposide, cytarabine, and melphalan (BEAM) (38%, n = 47), ifosfamide, carboplatin, and etoposide (ICE) (24%, n = 29), melphelan 200 mg/m2 (M200) (12%, n = 15) and total body irradiation + cyclophosphamide (TBI+C) (29%, n = 24) were used as conditioning regimens. Results: All of the patients experienced anorexia at any grade. TAS in the sixth day was higher than TAS in the first day (p < 0.05). Patients with multiple myeloma experienced anorexia especially more than those with other diagnoses on days 1, 2, 5 and 6; Women experienced anorexia more than men on days 3 and 4. TAS on days 1-3 and on days 7-10 was more severe in patients underwent M200 than in patients underwent BEAM. TAS on days 1-2 was more severe in patients underwent ICE than in patients underwent BEAM (p < 0.05). The mean percentages of patients who scored severe or very severe anorexia in 10 days was 22,3% in BEAM, 24,5% in ICE, 52% in M200 and 24,3% in TBI+C groups. Conclusions: All patients that underwent HDC faced anorexia. TAS in the sixth day was higher than TAS in the first day after stem cell reinfusion. The M200 conditioning regimen caused more frequent and severe anorexia compared to BEAM, ICE and TBI+C regimens. No significant financial relationships to disclose.
Relationship between differences in RNA or protein expression and the effects of race/ethnicity on breast cancer outcomes.
Authors: M. Chavez-MacGregor, S. Liu, H. Chen, K. Do, L. Pusztai, W. F. Symmans, G. N. Hortobagyi, G. B. Mills, F. Meric-Bernstam, A. M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2011)

157 Background: Race is associated with distinct outcomes for breast cancer patients. The purpose of this study was to evaluate whether there were differences in gene or protein expression patterns between breast cancers according to race/ethnicity and cancer subtype [(triple-negative (TN), estrogen receptor-positive/HER2-negative (HR+) and HER2-positive/with any ER status (HER2+)]. Methods: Fine needle aspirates from primary breast cancers were obtained under a prospective tissue collection protocol. Transcriptional profiling was performed using Affymetrix HG-U133A platform in 376 patients and reverse phase protein array analysis (RPPA) was done for 177 distinct proteins in 255 patients from a separate cohort. Unsupervised clustering was conducted, as well as supervised comparison by race and tumor subtype. BRB-Array tools and Ingenuity Pathways software packages were used to analyze the data. Results: Median age was 50 years in both cohorts. In the RPPA cohort 54.5% of the tumors were HR+, 20.7% HER2+ and 24.71% TN. One hundred and forty-seven (57.6%), 47 (18.43%), 46 (18.1%) of the patients were white, Hispanic, and black, respectively. Unsupervised hierarchal clustering of the protein expression data showed no distinct clusters by race (permutation p values were 0.492, 0.489 and 0.494 for the HR+, HER2+ and TN tumors respectively). In the gene expression cohort, 54.2% of the tumors were HR+, 16.5% HER2+ and 29.3% TN. Two hundred and sixteen (57.5%), 111 (29.52%), and 32 (8.52%) patients were white, Hispanic and black, respectively. No probe set with an FDR &lt; 0.05 showed any association with race by breast cancer subtype; similar results were obtained using pathway and gene set enrichment analysis methods. Conclusions: These results indicate that there are no large scale gene and protein expression differences between breast cancers of different races. The study size is too small to confidently exclude small scale expression differences in a limited number of proteins or RNAs. This analysis also did not examine the potential differential distribution of DNA nucleic acid polymorphisms, somatic mutations, gene rearrangements or copy number aberrations by race-ethnicity.
Development of chemotherapy-induced extravasation management algorithm to facilitate and improve care of cancer patients.
Authors: Sara S Kim, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2014)

224 Background: Chemotherapy administration has up to a 6% incidence of extravasation, which can cause ulcer formation, tissue necrosis and loss of limb function, requiring surgical intervention (debridement and skin grafting). Because of its rare occurrences and the lack of uniform consensus on management strategies, much time is spent on decision making process by the patient care team and treatments are often delayed. To facilitate and improve the care of cancer patients in cases of chemotherapy extravasation, a task force was created to develop chemotherapy extravasation management algorithm. Methods: Chemotherapy extravasation management task force comprised of oncology pharmacy and oncology nursing leaderships. Literature search (limited to English language) was performed in PubMed (through April 2014) and of 34 “hits”, 13 articles on management of chemotherapy extravasation were reviewed. An algorithm was developed which contained 7 distinct intervention pathways dependent upon the drug involved in extravasation. The treatment algorithm was adopted after review by the cancer institute’s QI committee and oncology pharmacy and therapeutics subcommittee. Results: Chemotherapy extravasation algorithm provides the following guidance to nurses and providers: (1) Initial steps for nurses to follow in case of chemotherapy extravasation; (2) Chemotherapeutic agent-specific recommendations for cold or hot compress with antidote if indicated; (3) Nursing instruction for documentation of the adverse event and recommendation to photograph the site of extravasation; (4) Preparation and administration instruction of the antidotes (hyaluronidase, dexrazoxane, sodium thiosulfate, and DMSO). Finalized chemotherapy extravasation algorithm was made available in all oncology treatment areas and included in each extravasation kit. Conclusions: The development of algorithm for chemotherapy extravasation management provides clear and comprehensive instructions to oncology nurses and oncology providers on management and shortens the time to initiate management, thereby minimizing the risk of potentially debilitating sequelae from delayed management.
Molecular diagnosis with the 92-Gene Assay (92-GA) and decision-impact on treatment: Final results from a prospective, multi-disciplinary study.
Authors: Sachdev P. Thomas, Fadi S. Braiteh, Lauren Jacobson, Anthony R. Victorio, Karen Ann Cherkis, Theresa N. Operana, Nichole Renee Blatner, Brock Schroeder, Catherine A. Schnabel
Journal: Journal of Clinical Oncology (2016)

205 Background: Metastatic lesions with unknown or differential diagnoses pose significant challenges leading to suboptimal treatment and outcomes. Molecular diagnosis with the 92-GA has shown improved accuracy compared to IHC and improved survival in pts treated based on assay results. The following prospective, multi-institutional study assessed the utility and impact of the 92-GA in diagnosis and treatment decision-making in community clinical practice. Methods: Over 18 months, physicians (68 medical oncologists, 25 pathologists) completed standardized, discipline-specific questionnaires via a web-based data portal for 444 cases in which the 92-GA was ordered as part of routine clinical care for pts with unknown or differential diagnoses. Physician-reported utility and impact were characterized for oncologists and pathologists. Results: 92-GA molecular diagnoses included 22 different tumor types: pancreaticobiliary (21%), lung squamous (9%), lung adenocarcinoma (9%), and intestinal (9%) were most common. Factors contributing to ordering the 92-GA were interdisciplinary: for oncologists, no primary following clinical review and imaging (42%), pathology report of a differential diagnosis (21%) or unknown primary (20%), and differentiation between a new cancer or recurrence (16%) were most common; for pathologists, IHC inconclusive (50%; median 9 IHC stains) and oncology ordered due to unknown primary (30%) were most common. Oncologists reported that the diagnosis provided by the 92-GA resulted in changing the treatment option in 46% of cases. 75% of pts received therapy with a median time from biopsy to treatment of 25d. Following the 92-GA, predictive biomarkers (eg, EGFR, ALK) were ordered in 81% of cases diagnosed as lung and 67% diagnosed as colorectal cancer. Conclusions: This study demonstrated significant clinical utility of the 92-GA: changing treatment options in approximately half of pts. Clinical utility spanned a spectrum of diagnostic uncertainty for oncologists and pathologists, and helped narrow differential diagnosis. Additional biomarker testing was common after a diagnosis of lung or colorectal cancer was rendered by the 92-GA.