tbuckley/cabot-search huggingface dataset:
Cost-effectiveness analysis of cetuximab as third-line treatment in metastatic colorectal cancer
Authors: M. Romeo, G. Soler, M. Martínez Villacampa, B. Laquente, A. López Doriga, A. Pisa, M. Rey, C. Santos, R. Salazar, J. R. Germà Lluch
Journal: Journal of Clinical Oncology (2008)

15090 Background: Cetuximab monotherapy provides 1.5 month survival improvement against best supportive care (BSC) in metastatic colorectal cancer (mCRC) (Jonker et al NEJM 2007; 357: 2040–48). Cetuximab-irinotecan combination prolongs time to progression but its effect on survival has no been ellucidated in fase III trials. New drugs have increased expenses in oncological departments. Cost- effectiveness analysis are needed. Methods: Retrospective comparative study of 35 patients treated with weekly cetuximab- irinotecan versus 30 consecutive historic controls treated with BSC, after progression to 5-fluorouracil, irinotecan and oxalipatin in mCRC. Primary end-points were analysis of survival (time from progression to second line treatment or start of cetuximab until death) and the cost of each week gained with cetuximab-irinotecan. Data analysed were number of blood analysis, CT scans, Rx, MRI, medical outpatient visits, hospital admissions and emergency episodes. Nonparametric tests were used. Results: Both groups were well-balanced as for gender, age (median 59), stage, adjuvant treatment and primary tumour location. All 65 patients received 2 palliative lines. No statistically significant differences in median number of cycles were found. One site only metastatic location was present in 43.3% controls and 22.9% cases. PS was higher or equal to 2 in 63.4% controls and 8.6% cases (p<0.001). Median number of cetuximab infusions were 6 (range 35). Eighty percent cases progressed on cetuximab treatment. The most common toxicity was dermathologic (88.6%), and the most common grade 3–4 toxicities were G-I and constitutional (each 40%). Median survival was 6.99 months (range 17.91) for cases and 3.02 (range 27.89) for controls (p<0.03). Cost of one week of life since start of cetuximab (cases) or since last progression to chemotherapy (controls) was 473.69 euros (range 1232.16) for cases and 173.04 (range 1781.19) for controls (p<0.001). Conclusions: The control group had worse predefined prognosis than the treatment group due to lower PS. The cost of survival benefit of cetuximab-irinotecan as third line treatment will be compared against an extended control cohort with well-balanced prognostic factors including PS. Results of these analysis will be presented. No significant financial relationships to disclose.
Pan-HER tyrosine-kinase inhibitors (TKI) dacomitinib and afatinib in penile squamous cell carcinoma (PSCC): Results from an ongoing open-label, single-group, phase 2 trial of dacomitinib in chemonaive patients (pts).
Authors: Daniele Raggi, Andrea Necchi, Patrizia Giannatempo, Nicola Nicolai, Maurizio Colecchia, Giuseppina Calareso, Elena Togliardi, Flavio Crippa, Luigi Mariani, Federica Perrone, Giuseppe Pelosi, Roberto Salvioni, Guru Sonpavde
Journal: Journal of Clinical Oncology (2016)

483 Background: Prognosis of pts with advanced/metastatic PSCC is poor and chemotherapy exerts a low efficacy. Targeting HER pathway is rational and promising in PSCC. Two companion trials are enrolling in the 1st-line/neoadjuvant setting (Dacomitinib, NCT01728233) and salvage setting (Afatinib, NCT02541903). Here we present the ongoing results of the former study. Dacomitinib is a potent, irreversible TKI of human EGFR/HER1, HER2 and HER4. Methods: 37 pts with clinical N 2-3 or M1 disease receive oral Dacomitinib 45 mg daily until surgery or disease progression (PD)/unacceptable toxicity. No prior systemic therapy is allowed. Computed tomography and PET scan are repeated q2 months. Simon’s Optimal 2-stage design is applied. The primary endpoint is the objective response-rate (ORR = CR/PR according to RECIST v1.1: H0 ≤ 5%, H1 ≥ 20%, α and β = 10%). Next generation sequencing (NGS) with “Hot-spot cancer panel” (Ion Torrent, Life Technologies) is being performed for all enrolled pts. Results: From 06/13 to 05/15, 14 pts were treated. Median age was 57 yrs (IQR: 54-72). 4 had received inguinal/pelvic lymphadenectomy, 4 had inguinal+pelvic nodes, 10 bilateral disease, and 4 distant mets. Two pts achieved a PR (ORR: 14.3%), 8 a SD, 4 a PD. 8 pts (57.1%) had a metabolic PR. 9 pts underwent post-Dacomitinib lymphadenectomy: &gt; 90% necrosis was seen in one patient. After a median follow-up of 6.97 months, 6 pts (42.8%) were progression-free (median PFS was 4.47 months). Median OS was 11.9 months, 1-year OS was 50% (95%CI: 8.05-82.63). Skin toxicity was observed in 7 pts (6 G1, 1 G3), G2 diarrhea in two, and bleeding of cutaneous mets in one. Tissue from one PR pt harbored missense mutations in FBXW7 (R505S), PTEN (A3T), and TP53 (R273H, loss of function mutation) genes. Conclusions: Dacomitinib is endowed with antitumor activity in PSCC. Results are pending confirmation in the whole sample size. Dacomitinib and Afatinib trials will provide insights into the targeting of HER pathway in PSCC based on prior chemotherapy administration. Preliminary data on molecular alterations linked to clinical benefit are being observed. Clinical trial information: NCT01728233.
A randomized phase II trial comparing two paclitaxel (P)-cisplatin (C) containing chemoradiation (CRT) regimens as adjuvant therapy in resected gastric cancer (RTOG Intergroup #0114)
Authors: G. K. Schwartz, K. Winter, B. Minsky, N. Janjan, P. Schaefer, J. Thomson, A. Rani, H. Gross, C. Willett, D. Kelsen
Journal: Journal of Clinical Oncology (2005)

4020 Background: The adjuvant arm of INT 0116, a 5-fluorouracil (5-FU)/LV containing CRT regimen, is the standard treatment for resected gastric cancer in the US. However, overall grade (gr) 3 or greater toxicity (tox) is 73% [32% gastrointestinal (GI) and 53% hematologic (heme)]. Death occurs in 1% of treated patients. The benefit and safety of newer regimens remain to be tested. Methods: We performed a randomized phase II study comparing two P-C regimens, one with (Arm 1) and the other without (Arm 2) 5-FU. The primary objective was to show a 15% improvement in 2 year DFS, as compared to INT 0116. The secondary objective was to determine whether the toxicity rates were the same or better than INT 0116. An early stopping rule was designed to close a study arm if gr 3/4 GI toxicity exceeded 47%. RT was the same on both arms (45 Gy in 1.8 Gy fractions, 5 days/wk for 5 weeks) and was started within 6 weeks of completing the post-op chemotherapy (CT). The two regimens were as follows: Arm 1, post-op 5-FU 600 mg/m2 as continuous infusion (CI) days 1–5, 29–33, C 15 mg/m2 days 1–5, 29–33 and P 175 mg/m2 days 1 and 29. CT with the RT: 5-FU 300 mg/m2 as a 5 day CI, weeks 1 to 5, and P 45 mg/m2 days 1, 8, 15, 22, 29. Arm 2: post-op P 175 mg/m2 and C at 75 mg/m2 days 1, 29. CT with the RT: P 60 mg/m2 as a 96 hour CI weeks 1–5, and C 30 mg/m2 days 1, 8, 15, 22, 29. Results: From 5/01 until 2/04 (study closure), 78 patients entered this study from 28 institutions. At the planned interim analysis, it was found that on Arm 1 17/28 (60%) patients had gr 3 and 1 had gr 4 GI tox. In addition, 6/28 (21%) had gr 3 and 13/28 (46%) had gr 4 heme tox. Since this exceeded the preset levels of acceptable tox, Arm 1 was closed to patient entry (5/03). Accrual continued to Arm 2. On Arm 2, 10/46 (22%) had gr 3 and 3/46 (7%) had gr 4 GI tox. Gr 3 and 4 heme tox was 10/46 (22%) and 4/46 (9%), respectively. Overall, gr 4 tox was 15/28 (54%) on Arm 1 and 9/46 (20%) on Arm 2. Conclusions: Arm 2, containing P and C but no 5-FU, appears to be safe and well-tolerated in patients with resected gastric cancer. If the 2 year DFS is 67% (available for analysis by 2/06), then this CRT regimen will be proposed as the investigational arm for future randomized phase III trials. No significant financial relationships to disclose.
A second peritoneal cytology as a prognostic factor in epithelial ovarian cancer.
Authors: S. Sirop, M. Kanaan, D. Wiese, N. Dutt, V. Karla, T. T. Singh, S. Nagpal, M. L. Arora, S. Saha
Journal: Journal of Clinical Oncology (2011)

e15558 Background: A positive (+ve) peritoneal cytology (PC) is an important prognostic factor with impact on survival in ovarian cancer (OvCa). The role of a second (2nd) PC after debulking surgery is unknown. Methods: A retrospective analysis of OvCa patients (pts) between 2001-2009 who underwent debulking surgery with two PC: one before beginning and one after debulking surgery was undertaken. Primary outcome was overall survival. For survival analysis only stage III and IV pts were included. Results: Of 50 pts included in our study, 21 (gp A) had both PC -ve, 19 (gp B) had the first PC +ve and the 2nd PC -ve, and 10 (gp C) had both +ve for malignancy. All pts reveived platinium based chemotherapy. There was no significant difference in demographics or grade of disease. There was more serous histology in gp B, compared to gp A and C. Bowel resection was done in 42%, 44%, and 80% in gp A, B, and C respectively; whereas, optimal cytoreduction rates were achieved in 83%, 75% and 60% respectively. Minimum and median follow-up was 12 and 23 months respectively. The percentage of persistent/recurrent disease was 33%, 44%, and 70% in gp A, B, and C respectively. There was improved median overall survival in gp A as compared to gp B (48 vs. 32 months) and in gp A as compared to gp C (48 vs. 13 months). Conclusions: This is the first study to show that a 2nd -ve PC after debulking surgery following an initial +ve or -ve PC is a possible independent prognostic factor. Hence a 2nd PC should be obtained during surgical treatment of ovarian cancer. Demographics, stage, histology, perioperative outcome, and survival of group A versus group B versus group C. Variables Group A Group B Group C Demographics Total No. of pts Mean age (years) 21 61.2 19 65.6 10 69.6 Stage I II III IV 38% 4.7% 47.8% 9.5% 0% 16% 53% 31% 0 0 80% 20% Histology (most common type) Serous histology 38% 95% 60% Peric-operative outcome LOS EBL (ml) OCR 9 300 83% 10.1 700 75% 11.75 400 60% Only stage III and IV disease Radical bowel resection 42% 44% 80% Neoadjuvant chemotherapy 67% 69% 90% Median CA-125 328 143 365 Follow-up Lost to follow-up Persistence/recurrence Median survival (months) 16.6% 33% 48 12.5% 44% 32 10% 70% 13 Abbreviations: Pts, patients; LOS, length of stay; EBL, estimated blood loss during surgery; OCR, optimal cytoreduction.
Bone mineral density in patients with thyroid cancer on suppressive therapy after total thyroidectomy.
Authors: B. Spanikova, S. Spanik, P. Hnilica
Journal: Journal of Clinical Oncology (2011)

e19739 Background: The standard therapy of thyroid carcinomas (TC) consists of total or nearly total thyroidectomy. Then the whole-life substitution therapy by oral thyroxine (T4) is given. Another goal of this therapy is to suppress serum thyroid stimulating hormone (TSH) to prevent the growth factor-like effect of TSH on TC cells. The recommendation is to administer supraphysiologic amounts of oral T4. This leads to hyperthyroidism, which is subclinical. Thyroid hormones are also involved in regulation of bone metabolism and longstanding subclinical hyperthyroidism may result in increased bone turnover and decreased bone mineral density (BMD). The aim of the study was to assign the damage of bone metabolism in TC patients. Methods: Bone mineral density (BMD) was measured by dual energy photon x-ray absorptiometry in the lumbar spine and hips. BMD was classified using T score in postmenopausal women and more than 50 years old men. We classified Z score in premenopausal women and younger than 50 years men. C-terminal cross-linked telopeptides of type I collagen (CTX) were measured using ELISA. Additionally serum TSH and fT4 (free T4) were measured. Relationships between baseline characteristics (age, menopausal status in women, TSH levels and duration of suppressive therapy) and BMD were assessed using univariate and multivariate analysis tools. Results: We included 165 TC patients in the study. There were 13 men and 152 women, the mean duration of thyroid suppressive therapy was 7. 2 years (0 – 24 years). The patients exhibit osteporosis in 31%, whereas 30% had normal BMD. The incidence of osteoporosis appeared to increase with age but did not correlate with duration of thyroid suppressive therapy. TSH levels slightly correlated with decrease in BMD. Conclusions: The long term survivors from TC after total thyroidectomy on thyroid suppressive therapy have higher risk of osteoporosis and therefore we recommend BMD testing and appropriate measures according to results.
Endpoints for Colon Adjuvant Clinical Trials (CACT): Recommendations based on individual patient data (IPD) from 20898 patients (pts) and 18 randomized trials
Authors: D. J. Sargent
Journal: Journal of Clinical Oncology (2005)

3512 Background: The traditional endpoint for CACT is OS, with 5 years (yr) used to demonstrate adequate follow-up (f-u). We have shown previously that disease free survival (DFS) outcomes after 3 yr minimum (min) f-u are excellent predictors of OS results. Here we explore shorter term DFS and OS endpoints, and the stage (stg) dependency of the concordance. Methods: IPD from 18 phase III CACT involving 25 treatment comparison conducted from 1978–96 were pooled. Trials included 43 arms: 9 no chemotherapy (CT) arms and 34 5-FU based CT arms; the pooled sample size was 20898 pts. Concordance measures included correlation (corr) of rates within arms, corr of hazard ratios (HR) from within study comparisons (comp), trial level significance (sig) comp (via log-rank testing), and trial level association from a formal surrogacy model. Results: The table presents primary results for DFS and OS at different time points. DFS with 3yr median (med) (opposed to min) f-u remained an excellent predictor of 5 yr OS. DFS at earlier time points was less accurate in predicting OS, but 2 YR DFS remained a strong predictor. No within trial comp without a sig difference in 1 yr min DFS was sig for 5 yr OS. OS with 3 yr min f-u was the most accurate predictor for 5 yr OS; OS with < 3 yr min f-u suffered from poorer prediction. Association between 3 yr DFS and 5 yr OS was greater for stg III pts; corr of HR within trials was 0.92 for stg III pts, 0.65 for stg II, likely due to a larger proportion of deaths without recurrence for stg II pts (17% stg III, 32% stg II, p < 0.001). Conclusions: DFS outcomes after 2 or 3 yr med f-u are excellent predictors of 5 yr OS outcomes. OS with 3 yr min f-u is the strongest predictor of 5 yr OS, but OS concordance degrades quickly with less f-u. 1 yr DFS comp detected all sig differences in 5 yr OS. DFS results are maximally relevant for trials where the majority of pts are stg III. DFS after 2 or 3 yr med f-u should be considered in designing future CACT. No significant financial relationships to disclose.
Impact of Molecular HLA Matching for Allogeneic Stem Cell Transplantation from Unrelated Donors.
Authors: Yves Chalandon, Joerg Halter, Tayfun Guengoer, Andre Tichelli, Grazia Nicoloso de Faveri, Bernard Chapuis, Reinhard Seger, Urs Schanz, Alois Gratwohl, Eddy Roosnek, Jean-Marie Tiercy, Jakob R. Passweg
Journal: Blood (2004)
Changes of pulmonary function test and development of non-infectious pneumonitis in patients with metastatic renal cell carcinoma treated with everolimus.
Authors: Kwon-Oh Park, Jae-Lyun Lee, Jin-Hee Ahn, In Gab Jeong, Cheryn Song, Bum-Sik Hong, Jun Hyuk Hong, Hanjong Ahn
Journal: Journal of Clinical Oncology (2014)

530 Background: The aim of this study was to evaluate the changes of pulmonary function test (PFT) during everolimus treatment and to assess whether the change of PFT is associated with the development of non-infectious pneumonitis in patients with metastatic renal cell carcinoma. In addition, we tried to determine whether everolimus-associated pneumonitis could affect the efficacy of everolimus. Methods: Patients with mRCC who had received everolimus (10 mg dose once daily) after failure to VEGF-TKI treatment and underwent baseline PFT with regular PFT follow up were included in this study. The diffusing capacity divided by the alveolar volume (DL CO /VA) was used among various parameters of PFT. Repeated-measures ANOVA was used to describe changes of DL CO /VA. A Cox proportional hazard model with pneumonitis onset as a time-dependent covariate used to assess the prognostic role of pneumonitis. Results: This study included 36 patients. Nine patients (30%) developed everolimus-associated pneumonitis (pneumonitis group) and 27 were included in non-pneumonitis group. Five patients (14%) among pnemonitis group were symptomatic. The baseline DL CO /VA of patients was 90.0%. It decreased to 80.2%, 76.4%, 76.0%, and 72.1% after everolimus treatment of 6, 12, 18, and 24 weeks, respectively. DL CO /VA declined significantly as the treatment duration becomes longer (p &lt; 0.001). There was no significant difference in change of DL CO /VA between patients with pneumonitis and those without pneumonitis (p =0.435). On time-variant Cox analysis, the decrease of DL CO /VA was not correlated with the efficacy of everolimus in terms of progression free survival (PFS, HR=1.0, p=0.94) and overall survival (OS, HR=0.98, p=0.18), while development of pneumonitis was associated with poor PFS (HR=4.60, p=0.005). Conclusions: Although the eveolimus treatment decreased DL CO /VA, the decline of DL CO /VA was not associated with the development of pneumonitis. Changes in DL CO /VA were not related with efficacy of everolimus, while the development of pneumonitis was a prognostic factor for PFS.
Successful Percutaneous Coronary Intervention Improves Cardiopulmonary Exercise Capacity in Patients With Chronic Total Occlusions
Authors: Kambis Mashayekhi, Hans Neuser, Anna Kraus, Matthias Zimmer, Jörg Dalibor, Ibrahim Akin, Gerald Werner, Toma Aurel, Franz-Josef Neumann, Michael Behnes
Journal: Journal of the American College of Cardiology (2017)
Frequency of mutations associated with targeted therapy in malignant melanoma patients.
Authors: S. Cheng, P. Chu, M. Hinshaw, K. Smith, J. Maize, A. Sferruzza
Journal: Journal of Clinical Oncology (2011)

8597 Background: BRAF, RAS, KIT, and TP53 genes are frequently mutated in primary malignant melanomas, and activating mutations involving RAS and BRAF V600, as well as imatinib-sensitive KIT mutations, have been exploited for targeted therapy. Here we studied the prevalence of mutations in these four genes in primary malignant melanoma samples to establish a strategy to identify patients who might benefit from targeted gene therapy. In addition, results were cross-referenced with pathological and histogenetic indicators. Methods: 198 confirmed formalin-fixed, paraffin embedded (FFPE) primary melanoma tissue samples were screened for mutations in BRAF (exons 11, 12 and 15), RAS (H-, K-, N-, exons 1 and 2), KIT (exons 8, 9, 11, 13, and 17), and TP53 (exons 4-9) using direct DNA sequencing. Results: Overall, 140 (70.7%) of the 198 melanoma samples had mutations in one or more of the genes analyzed. BRAF mutations were the most prevalent, with the majority involving codon V600 (Table). Among the BRAF V600 mutations, 66% were V600E and 30% were V600K. NRAS and KIT had similar mutation frequencies. Most NRAS mutations occurred at position Q61, of which 50% were Q61L and 33% were Q61R. About one-third of the KIT mutations were those likely to be sensitive to imatinib. BRAF V600, NRAS Q61, and imatinib-sensitive CKIT mutations were mutually exclusive. TP53 mutations were observed in approximately one-third of samples, often concurrent with other mutations. Conclusions: BRAF, NRAS, CKIT, and TP53 genes are frequently mutated in primary malignant melanomas. The predominance of BRAF V600, NRAS Q61, and imatinib-sensitive KIT mutations signifies the potential for targeted therapeutic strategies in melanoma patients. The high percentage of BRAF V600K mutation illustrates the importance of expanding clinical trials of BRAF inhibitors to include patients with V600K and possibly other V600 mutations. The mutually exclusive pattern of mutations also provides a hierarchical screening strategy for samples that have limited tissue availability. Gene Prevalence, % Predominant mutations BRAF 44.9 V600 (88%) NRAS 18.7 Q61 (89%) CKIT 17.1 Imatinib sensitive (33%) TP53 34.6 None
Occurrence of sarcopenia in patients with non-small cell lung cancer (NSCLC) treated with erlotinib with normal or increased body mass index (BMI).
Authors: J. Hadoux, B. Besse, E. Lanoy, F. Fayard, L. Martin, V. E. Baracos, S. Antoun
Journal: Journal of Clinical Oncology (2011)

e19613 Background: Sarcopenia (S), defined as a skeletal muscle wasting, is an independent prognostic factor in patients (pts) with solid tumors. Inhibition of Akt/mTOR pathway (modulated by erlotinib) can inhibit muscle anabolism and favor muscle atrophy. Characteristics of NSCLC pts at erlotinib initiation and evolution of sarcopenia under treatment is unknown. Methods: We have retrospectively investigated S and muscle loss in 32 NSCLC pts treated with erlotinib with or without everolimus in 2nd or 3rd line. CT image analysis was used to define change in total skeletal muscle. The 3rd lumbar vertebra (L3) was chosen as a landmark. Images were analyzed using Slice-O-Matic software V4.3 (Tomovision). Tissue cross-sectional areas (cm2) were computed. S was defined by L3 muscle index < 55.4cm²/m² (men) or 38.9 cm²/m² (women) on CT scan analysis. Results: There were 17 men and 15 women, 40.6% were never smokers. 75% had an adenocarcinoma. 17 pts received erlotinib alone and 15 pts combined with everolimus. Median weight was 67 (interquartile range (IQR)=53-81) kg, 62% had a BMI within normal range (18.5-25), 19% were overweight (25-29.9), and 19% were obese (≥30.0). We identified 46.9% of pts. as sarcopenic. Serum albumin was within the normal range (35-40g/l) in 52.9% of pts without S vs 33.3% of pts with S (p=0.37). CT scan analysis revealed a 3.8% (IQR=0.3-9.1) decrease in muscle surface area during the first 6 weeks of treatment (W6), which correlated with weight loss, r=0.603 (p<0.002). We identified 25% of pts with elevated serum creatine phosphokinase at W6 (normal level at baseline) but no correlation with muscle loss could be determined due to small number of pts. Digestive toxicity was grade 1 (25%) and grade 2 (6.25%) diarrhea. Conclusions: Our data show that despite normal or high BMI, S is present in about a half of NSCLC pts. Muscle loss could be explained by rhabdomyolysis (25% of increase CPK), decreased dietary intake, or inhibition of muscle anabolism with targeted therapy. S will be further evaluated in pts with long exposure to erlotinib.