tbuckley/cabot-search huggingface dataset:
Correlation between changes in 2- or 3-year disease-free survival (DFS) and 5-year overall survival (OS) in adjuvant breast cancer trials from 1966–2006
Authors: R. C. Ng, G. R. Pond, P. A. Tang, P. W. MacIntosh, L. L. Siu, E. X. Chen
Journal: Journal of Clinical Oncology (2007)

581 Background: Although disease-free survival (DFS) is accepted as a valid endpoint in adjuvant breast cancer trials, improvement in 2- or 3-year DFS has never been formally established as an adequate surrogate for 5- or 10-year overall survival (OS). We set out to establish if changes in 2- or 3-year DFS can be used to accurately predict changes in 5- or 10-year OS. Method: We conducted a systematic Medline search for phase III randomized adjuvant breast cancer trials published between 1966–2006 with &gt;100 patients per arm with data for 2- and 3-year DFS as well as 5- or 10-year OS. Only trials of systemic therapies (e.g. chemotherapy, hormonal therapy) were included. We excluded studies investigating the effects of surgery, radiotherapy and neoadjuvant treatment. A univariate regression model weighted by trial sample size was constructed to determine if changes in 2-year DFS between treatment arms within trials were predictive of changes in 5- year OS. Computations of the correlation coefficient, proportion of variation, predicted estimates and 95% prediction interval were undertaken. Results: 126 studies containing 149 treatment arms met the inclusion criteria. Median sample size per trial was 533 and median follow up time was 81 months. Only 26 trials provided 10-year OS data thus association with 10-year OS was not attempted. Results were similar between analyses using either 2- or 3-year DFS, hence only 2-year DFS statistics are reported. 2-year DFS was a significant predictor of 5-year OS regardless of what other covariates were included (p&lt;0.001). For every 1% increase in difference between treatment arms in 2-year DFS, the estimated difference in 5-year OS increased by 0.52%. The proportion of variation explained (R2) ranged from 0.38 to 0.49, with a wide prediction interval. Indeed, if a future trial accrued 1,000 patients and the 2-year DFS in the experimental arm was better than the control by 10%, the 95% prediction interval would still range from -0.2% to 11%. Conclusion: There is a statistically significant correlation, of moderate strength, between changes in 2-year DFS between treatment arms and changes in 5-year OS but the wide prediction intervals mean that the correlation is not strong enough to be used as a surrogate. No significant financial relationships to disclose.
Capcitabine and oxaliplatin (XELOX) in the treatment of advanced gastric cancer
Authors: R. Quek, W. T. Lim, K. F. Foo, W. H. Koo, H. C. Toh
Journal: Journal of Clinical Oncology (2006)

14089 Background: Effective 1 st line chemotherapy that is easily delivered and tolerable is important in patients with advanced gastric cancer (AGC). This study aimed to evaluate the toxicity and efficacy of combination capecitabine and oxaliplatin (XELOX), given 3 weekly, in patients with AGC. Methods: Twenty-seven patients with AGC, were treated with XELOX at the National Cancer Centre Singapore between June 2003 and December 2005. Capecitabine was given 2000 mg/m 2 /day, days 1–14, and oxaliplatin was given 130 mg/m 2 on day 1, every 21 days. Results: The median age was 61 years with 22% of patients ≥ 70 years. One-third of patients had ECOG 2 - 4, and 33% of patients had signet ring cell histology. Median doses of capecitabine and oxaliplatin achieved were 1500 mg/m 2 /day (1200 - 2400) and 130mg/m 2 (80 - 130) respectively. A median of 5 cycles (range 1 - 8) of XELOX was administered. All 27 patients had toxicity assessment. Toxicities were infrequent and mild. There were 3 cases of grade 3/4 toxicities (thrombocytopenia, neutropenia and fatigue). Twenty-two patients had measurable disease for response evaluation. Complete (CR) and partial (PR) response rates were 9 and 50% respectively. Overall response rate was 59%. Chemo-naïve patients had better responses (80% vs 25%). Four of the remaining 5 patients had reduction in non-measurable disease or in tumor marker levels. Of the 9 patients with ECOG &gt; 1, there was radiological CR in 1 patient and 5 PR; 1 had normalization of CEA, another reversal of disseminated intravascular coagulation and the third decreased ascites. The median time to progression and overall survival were 5.9 months and 7.6 months respectively. Conclusions: XELOX regimen is safe, active and well tolerated in AGC even in patients with poor ECOG status. It is easily administered without requiring a central venous catheter. This regimen should be investigated further in a prospective manner. No significant financial relationships to disclose.
Electrochemotherapy with bleomycin: A local treatment with possible systemic implication.
Authors: A. Testori, F. Verrecchia, J. Soteldo, G. Spadola, C. Martinoli, S. Gandini, C. Passoni, F. Cataldo, A. Di Pietro, P. Ferrucci
Journal: Journal of Clinical Oncology (2010)

8589 Background: A new, promising application of bleomycin was discovered and developed by Mir in 1991, combining the drug with electroporation. This new technique was called electrochemotherapy (ECT). The new treatment is based on the increased bleomycin delivery into tumor cells after cell membrane permeabilization by electric pulses administered locally at the site of superficial tumor localizations. Since 1991 more than 300 articles were published on the argument and experiences from many institutes in Europe seems to be very promising. Actually ECT is used for the treatment of cutaneous and subcutaneous tumoral lesions from different tumoral types. Favorable results in treating superficial metastatic lesions have been published with a complete response rate for treated nodules raging from 70% to 90%. Methods: In our Institute we treated 75 consecutive patients from 2006 to 2009 for superficial cancer lesions, especially metastatic melanomas (58 patients) and squamous or large basal cell carcinomas (15 patients). Results: We obtain an overall response rates (OR) of 90% with complete response rates (CR) of 72% in melanoma lesions and OR of 88% and CR of 65% in non melanoma lesions. Only 8/75 patients experienced relapse in the treatment field. The treatment was well tolerated either under general or local anesthesia with minimal side effects or discomfort for patients. Conclusions: We conclude that ECT is a safe and well tolerated procedure with quality of life improvement specially in palliative setting. Furthermore we are currently evaluating development of immune responses elicited by ECT, by comparing serum levels of pro- inflammatory cytokines, and frequency and activation of T cell populations in peripheral blood of selected patients, before and after therapy. This data will be presented and discussed. No significant financial relationships to disclose.
A follow-up study of rape victims
Authors: C C Nadelson, M T Notman, H Zackson, J Gornick
Journal: American Journal of Psychiatry (1982)

Of 130 women initially seen in a general hospital emergency room after being raped, the authors were able to interview 41 of the women 1-21/2 years after the rape. Half of the women continued to fear being alone and three-quarters reported still being suspicious of others. Many also felt restricted in their daily lives and had self-reported episodes of depression and sexual problems, which they attributed to the rape; none had a history of mental or emotional disturbance. The authors recommend that short-term, issue-oriented therapy be made available for all rape victims, as well as resources for the treatment of long-term symptoms.
Combination chemotherapy with sunitinib (IND 74019; NSC 736511) for untreated extensive-stage small cell lung cancer (SCLC): CALGB 30504 phase IB safety results.
Authors: N. Ready, F. Dunphy, H. Pang, R. Heinze, J. Crawford, E. E. Vokes
Journal: Journal of Clinical Oncology (2010)

7056 Background: CALGB conducted a phase IB trial to determine the dose of sunitinib that can be safely combined with cisplatin and etoposide in extensive SCLC. Methods: Patients with PS 0-1, adequate organ function and extensive SCLC were eligible. The treatment plan was cisplatin 80 mg/m2 d1 and etoposide 100 mg/m2 d1-3 every 21 d up to 6 cycles. Three cohorts of 6 patients at dose levels of 25, 37.5, or 50 mg/day days 1-14 every 21 days were planned. Every 2 week conference calls were held to assess toxicity. Toxicity during cycle 1 was evaluated for dose limiting toxicity (DLT). In cohort 1 prophylactic granulocyte growth factor support was not allowed. Results: In cohort 1, there were no protocol defined DLTs. However most patients had prolonged neutropenia and required delayed start of ≥ cycle 2 chemotherapy. In cohort 1, two patients requiring treatment delays for neutropenia were given granulocyte growth factor support during cycles 3-6 and were able to receive therapy as scheduled without DLT. The trial was amended to give prophylactic granulocyte growth factor support to all patients from cycle 1 onward while repeating the sunitinib 25 mg d 1-14 level 1 dose for cohort 2. Of 6 patients on cohort 2, two patients died from complications of febrile neutropenia and a third had febrile neutropenia with neutrophil count of zero cycle 3 d 10. When the second patient died on cohort 2, sunitinib concurrent with chemotherapy in this setting was deemed unsafe, and sunitinib was immediately and permanently stopped for all remaining patients. The trial has been amended to a randomized phase II trial in which maintenance sunitinib after chemotherapy is being evaluated. Conclusions: The combination of sunitinib 25 mg/day days 1-14 to standard dose cisplatin and etoposide appeared to cause prolonged neutropenia and an unacceptable rate of treatment-related mortality. Granulocyte growth factor given after chemotherapy in this setting did not prevent severe neutropenia and infections. This combination of chemotherapy and sunitinib is not recommended, even with growth factor support. No significant financial relationships to disclose.
Correlation of specific cytokine profiles with high blood neutrophil-to-lymphocyte ratio and outcome in metastatic colorectal cancer.
Authors: Zhi-Yu Chen, Christopher Hanyoung Lieu, Zhi-Qin Jiang, Cathy Eng, Jean-Nicolas Vauthey, George J. Chang, Wei Qiao, Jeffrey Morris, David S. Hong, Paulo Hoff, Hai T. Tran, John Heymach, Michael J. Overman, Scott Kopetz
Journal: Journal of Clinical Oncology (2012)

3598 Background: High blood neutrophil-to-lymphocyte ratio (NLR) has been previously identified as a poor prognostic marker in patients with metastatic colorectal cancer (mCRC). However, the underlying pathophysiology associated with this marker is not well defined. We validated this biomarker and investigated the relationship between circulating cytokines and high NLR. Methods: NLRs were calculated retrospectively from the ratio of peripheral blood absolute neutrophil and lymphocyte counts, and segregated based on previously determined cutoff of ≤5 and &gt;5. Four cohorts with a total of 805 CRC pts were evaluated to confirm the prognostic clinical significance of NLR. Plasma cytokine levels were evaluated in exploratory (n=39) and validation cohorts (n=166) of previously untreated mCRC patients using multiplex-bead assays, and correlated with NLR. Results: High NLR is present in 20% of CRC patients and is associated with poor prognosis, independent of known prognostic factors (Table). Expression of 6 cytokines (IL-6, IL-8, IL-2Ra, HGF, M-CSF and VEGF) correlated with NLR&gt;5 in both the exploratory and validation cohort. In the validation cohort, an additional 14 cytokines correlated with NLR&gt;5, including high EREG,AREG, and TGF-α, and low TRAIL. By hierarchial clustering, these 20 cytokines fall into 3 overlapping major clusters: angiogenic cytokines, inflammatory cytokines, and epidermal growth factor ligands. In the validation cohort, pts with a composite cytokine score below the median have longer survival than patients with high scores (40.0 mo vs 20.0 mo, HR = 2.24; 95% CI=1.47–3.41; P&lt;0.001). Conclusions: High peripheral blood neutrophil/lymphocyte ratio (NLR) is associated with poor outcomes independent of other known prognostic features. NLR correlates with discrete sets of cytokines which may reflect important biological features in poor prognosis mCRC. [Table: see text]
Association of <i>ABCG2</i> polymorphisms with exposure and toxicity of sunitinib in a patient with renal cell carcinoma.
Authors: T. Mizuno, T. Terada, T. Kamba, M. Fukudo, T. Katsura, E. Nakamura, O. Ogawa, K. Inui
Journal: Journal of Clinical Oncology (2010)

e15037 Background: Sunitinib, an oral multitargeted tyrosine kinase inhibitor, shows good clinical benefits in patients with renal cell carcinoma (RCC), but adverse events with a high frequency leading to the discontinuation of sunitinib therapy are considered as serious problem in the clinical practice. We experienced a RCC patient who showed severe toxicity and high exposure of sunitinib. To elucidate the cause of abnormal pharmacokinetics of sunitinib in this patient, we carried out pharmacogenomic analysis and transport experiments focusing on ABCG2 that is an efflux transporter expressed in the small intestinal epithelial cells. Methods: Five RCC patients treated with sunitinib of 50 mg once daily were enrolled in this study. Blood concentrations of sunitinib were measured by HPLC. Genetic polymorphisms of ABCG2 were examined by the direct sequencing. Transport of sunitinib by ABCG2 was assessed by cellular accumulation and efflux by HEK293 cells transiently expressing ABCG2. Results: One patient (patient 1) showed severe adverse events, such as hypertension (grade 3), facial acne (grade 3), elevation of amylase (grade 3), hypothyroidism (grade 2), thrombocytopenia (grade 2) and hyperpigmentation (grade 2). Area under the concentration-time curve (AUC0-24) of sunitinib in the patient 1 was approximately 2.5-fold higher compared with the other 4 patients (patients 2-5). Cellular accumulation of sunitinib was significantly lower in the ABCG2-expressing cells than in the control cells. This result suggests that sunitinib is exported by ABCG2. Efflux studies also suggest that sunitinib is transported by ABCG2. Genotype of ABCG2 421C>A, which reduces the transport function of ABCG2, was homozygous variant in the patient 1, and heterozygous variant (n=1) or wild-type (n=3) in the patients 2-5. Conclusions: This is the first demonstration that ABCG2 421A/A genotype is associated with increased absorption of sunitinib, and severe toxicity is caused by high drug exposure. Genetic polymorphisms of ABCG2 could be a risk factor for abnormal pharmacokinetics and severe adverse effects of sunitinib. No significant financial relationships to disclose.
Repeat transurethral resection of bladder tumors T1 G3
Authors: L. Boccon-Gibod, V. Boublil, M. Toublanc, V. Ravery
Journal: Journal of Clinical Oncology (2005)

4772 Objectives: To evaluate the diagnostic yield of repeat transurethral resection of bladder in patients diagnosed pT1 G3 bladder tumors. Patients and Methods: It is a retrospective study of 20 patients aged 53–84 diagnosed in our institution between 2000 and 2003 with a pT1 G3 bladder tumor assessed on the basis of submucosal invasion without extension into the muscular wall of the bladder documented on the pathologic slides. All these patients were submitted in the following 2 months to repeat transurethral resection interesting the site of the initial tumor as well as other detected lesions elsewhere in the bladder: with the aim to detect residual or a precocious recurrent tumor. Results: Out of these 20 patients, only 6 were free from tumor (pT0), 2 patients had an infiltrative bladder cancer pT2 G3, 2 had carcinoma in situ (CIS), 1 associated with a pTa G3 tumor, and 10 had a persistant/recurrent pT1 G3 tumor. If the understaging related to the initial TUR (10%) is low, it is important to note that in 14 patients (70%) residual tumor was documented. In 9 patients, out of 14 (64%) the tumor was detected on the site of the primary tumor, whereas in 5 cases out of 14 (36%), the tumor was located elsewhere in the bladder, and had probably in over looked during the first TUR. Conclusion: In our experience, a repeat transurethral resection after a primary diagnosis of a pT1 G3 bladder tumor is mandatory as residual tumors will be detected in almost 70% of the patients, in a significant proportion, the detected tumor had probably been overlooked at the primary endoscopy. No significant financial relationships to disclose.
Heterogeneous monitoring for and management of bevacizumab (BE) toxicity (T): Develpment of standardized guidelines for monitoring (mon) and treatment (tre) of the BE toxicity syndrome (BETS)
Authors: B. Ebrahimi, C. L. Martel, R. C. Horns, G. H. Upadhyaya, M. J. Vakil, L. D. Bosserman, C. A. Presant
Journal: Journal of Clinical Oncology (2005)

8224 Background: BE is widely used for managing metastatic colorectal cancer and is in widespread trials including breast, lung, renal and lymphoid malignancies. Analysis of patients (pts) receiving BE since FDA approval demonstrated hypertension (HTN) in 19%, proteinuria (PTN) in 19%, and both in 16%. Since there was a significant association of HTN and PTN (p<0.0005), we proposed the term BETS for this syndrome. We evaluated the pattern of mon and tre of BETS by different physicians in this pt cohort. Methods: 31 consecutive pts receiving BE following FDA approval in 6 cancer centers were evaluated for types of tests performed and frequency, and type of drugs used in tre. 10 oncologists and 3 nurse practitioners were surveyed for their preferences in HTN tre, and these were compared to national evidence based medical recommendations. Results: Mon of PTN was diverse, from pts with no evaluations to pts with urinalysis dipstick tests, to pts with 24 hr urine protein excretion. None had microalbumin determinations. BP was always monitored at the time of BE tre, but at no other times. Disparate tre were observed. Different classes of antihypertensives were used. Some pts with HTN received no tre, others had BE stopped. A standardized guideline for mon and tre was developed: mon before BE and q2wk with dipstick, 24 hr urine protein and microalbumin, and weekly BP check: and tre with ACE inhibitors for any PTN or for BP >130 systolic or >80 diastolic. Frequency of BETS pre and post standardization will be presented. Conclusions: BETS is common and may reduce duration of BE therapy if HTN or PTN become severe. Mon and tre require standardization to optimize BE dosing and duration of BE tre, and to reduce T. A standardized guideline has been proposed. 1767 characters without spaces Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech
Time to platinum resistance (TTPR) as a novel surrogate end-point for trials in ovarian cancer.
Authors: I. Pokataev, A. Tryakin, D. Kanagavel, A. Tjulandina, M. Stenina, M. Fedyanin, S. Tjulandin
Journal: Journal of Clinical Oncology (2010)

5082 Background: Planning new trials with overall survival (OS) as the primary end-point requires a long period of f.-up, with delay in results and increase in the cost of trials. This issue demands the necessity of introducing new surrogate end-points in clinical practice. Progression-free survival (PFS) does not always correlate with OS and should be used with caution as the primary end-point in ovarian cancer. The aim of this study was to evaluate and validate a novel surrogate end-point –TTPR defined as a period of time from start of first-line chemotherapy (CT) to date of platinum-resistant recurrence. Methods: The retrospective analysis included pts with ovarian cancer stages I-IV, who received platinum-based CT from 1995 to 2008 in our center. Pearson coefficients of correlation were calculated between PFS and OS and between TTPR and OS. Then both the TTPR and PFS were assessed as independent variables in a multiple linear regression with OS as a dependent variable. Only pts with known date of death were included in the analyses, which is a peculiarity of the used statistical methods. Results: Out of 320 pts included in the study 151 (47%) pts died. With median f.-up of 32 months, median PFS was 12 months, median TTPR - 21 months, median OS (expected) – 45 months. Pearson coefficient of correlation between PFS and OS was 0.66, between TTPR and OS – 0.82. There was statistically significant difference between two coefficients, p = 0.02. A multiple linear regression revealed that only TTPR can significantly predict OS (p < 0.001), impact of PFS in prediction of OS was statistically non-significant (p = 0.85). Conclusions: TTPR correlates with OS better than PFS. TTPR is longer than PFS but still much shorter than survival time. We expect that using TTPR as the primary end-point instead of OS will result in shortening of f.-up time and decrease number of pts in treatment arms. No significant financial relationships to disclose.
Surgical salvage of pelvic recurrences from colorectal tumors
Authors: M. Chacon, M. Varela, E. Huertas, E. Roca, F. Sanchez Loria, J. Kaplan, A. Pairola, J. O’Connor, C. Chacon, R. D. Chacon
Journal: Journal of Clinical Oncology (2006)

13580 Background: The morbidity of pelvic recurrences from colorectal tumors (PRCT) represents a challenge for the oncology multidisciplinary team. Surgical treatment is the best option for palliation and in several series it offers long term local control in 30% of the cases. Objective: To perform a retrospective analysis of patients (pts) surgically resected for PRCT in terms of: time to progression after surgical salvage (TP) and specific suvival (SS). Correlatives studies were performed with clinic and pathologic factors, surgical procedures (SP), and postoperative complications in terms of TP and SS. Methods: 64 pts treated (June 1994 - February 2005) were identified (women: 30), median age 63 years, site of the primary: rectum 48, sigmoid 16; Median number of resected nodes: 8 (r: 2 - 20) in pts with negative nodes and 15 (r: 6 - 42) in pts with positive nodes; primary treatment: surgery (S): 22 pts, S + chemotherapy (CT): 18, S + radiotherapy (RT): 4, S + CT/RT: 17, CT + S: 2 pts, QT/RT + CX: 1; in 7/64 a Miles procedure was performed as primary therapy, median disease free interval: 15 months; site of initial recurrence: locoregional 58 (90%), locoregional + systemic 10%. Pain and bleeding were the most frecuent symptoms. Results: The strategy in PRCT was: S: 29 pts, S + RT: 15, S + CT/RT: 9, CT/RT + S: 7, S + CT: 2, CT + S: 1, RT + S:1; IORT: 18/64; external beam RT: 17/64, 6 pts required Miles; type of resection: R0: 50/64 (78%), R1: 8/64 (12%), R2: 3/64 (5%) and 3 (5%) unknown. Median duration of surgery: 4 hours, abscesses and fistulas were the complications most frequently observed. Median time to progression (TP): 12 months, site of recurrence (56/64 pts) post salvage surgery: pelvic: 22 pts, extrapelvic: 6 pts, combined: 10 and unknown 18. Eleven pts are free of disease. In 16 pts more than one surgical salvage was perfomed. The specific survival was 21 months (IC 95% 37 - 61 m). Conclusions: In this serie surgical salvage of PRCT showed one year of local control disease, even in pts with R2 and with moderate morbidity. The surgical decision must be individualized and in the context of a trained surgical team. No significant financial relationships to disclose.