tbuckley/cabot-search huggingface dataset:
Pharmacogenomic trial of CPT-11-docetaxel in untreated patients (P) with advanced non small cell lung cancer (NSCLC). A phase II study of the Spanish Lung Cancer Group (SLCG). Correlation with the single nucleotide polymorphisms (SNPs) of UGT1A1, XPD2 and XRCC1
Authors: M. Domine, D. Isla, M. Cobo, C. Camps, N. Batista, J. Almenares, I. Barneto, J. L. Ramirez, J. J. Sanchez, R. Rosell
Journal: Journal of Clinical Oncology (2005)

7201 Background: The role of non-platin combinations has not yet been fully demonstrated. CPT-11 and docetaxel (Taxotere) have additive activity in vitro and in vivo. The optimal timing of administration of both drugs is not yet well defined. UGT1A1 has been shown to be the isoform responsible for SN38 (the major active metabolite of CPT-11) glucuronidation. XPD and XRCC1, are essential components in DNA repair system. The present study assessed whether these SNPs could influence the response, toxicity and survival in irinotecan-taxotere-treated advanced NSCLC P. Methods: Treatment consisted in CPT-11: 80 mg/m2 followed by Docetaxel 40mg/m2 d 1 and 8, administered every 3 weeks. TaqMan 5’ nuclease assay was used to examine SNPs in genomic DNA obtained from peripheral blood lymphocytes. 69 P were enrolled, 58 male and 11female. Median age was 66 years (range 39 - 79); 31 P had adenocarcinoma, 24 squamous cell carcinoma and 14 undifferentiated large cell carcinoma. 10 had stage IIIB and 59 stage IV. 248 courses have been administered (median 3, range 1- 8). To date all P were evaluable for toxicity and SNPs assessment and 59 for efficacy. Results: 13 (22%) P achieved a partial remission, without complete remissions. 18 (30.5%) showed stable disease and 28 (47.5%) progression. With a median of follow-up of 3,7 months the median time to progression (mTTP) was 4.8 months (95% C.I: 2.6–6.9) and median survival (MS) 6.9 months (95% C.I: 4 -9.8). Grade 3–4 toxicity was as follows: diarrhea 43%, neutropenia 15%, nausea and vomiting 16%, asthenia 12% of the P. Other toxicities were less common, and grade 1–2. Dose reduction was required in 23% of P with 10% of cycles delayed. However, the median of relative dose intensity was 0.95 for both drugs. No differences in toxicity, reponse rate, mTTP and MS were observed according to SNPs analyzed. Conclusions: CPT-11 - Docetaxel is active in untreated advanced NSCLC. The profile of toxicity was acceptable. This combination seems to be a good alternative to a platin-based chemotherapy. To date no differences in outcome were observed according to SNPs assesed. No significant financial relationships to disclose.
Role of adjuvant chemotherapy in locally advanced rectal cancer with ypT0-3N0 after neoadjuvant chemoradiation therapy.
Authors: Chang-gon Kim, Minkyu Jung, Inkyung Jung, Sang Joon Shin, Seung Hoon Beom, Joo Hoon Kim, Su Jin Heo, Ji Hyung Kim, Woong Sub Koom, Hyuk Hur, Byung Soh Min, Nam Kyu Kim, Ho Geun Kim, Joong Bae Ahn
Journal: Journal of Clinical Oncology (2016)

760 Background: Clinical benefit of adjuvant chemotherapy (AC) is still controversial in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiation therapy (CRT) followed by total mesorectal excision (TME). We aim to explore the role of adjuvant chemotherapy with fluoropyrimidine for ypT0-3N0 patients. Methods: Patients with ypT0-3N0 rectal cancer after neoadjuvant CRT and TME were included using retrospective cohort of Yonsei Cancer Center. Patients were categorized according to receipt of adjuvant chemotherapy (AC vs. no AC). Disease free survival (DFS) and overall survival (OS) between treatment groups were compared using all patients’ cohort (APC) and propensity score-matched patients’ cohort (PSMPC). Results: total of 339 patients were evaluated. Of all, 87 patients (25.7%) did not receive AC. There was no difference in DFS between two groups [hazard ratio (HR) = 1.079, p-value = 0.782 in APC; HR = 1.22, p-value in PSMPC]. Also there was no difference in OS between two groups (HR = 1.140, p-value 0.717 in APC; HR = 1.366, p-value 0.472 in PSMPC). Advanced T stage and positive resection margin were associated with inferior DFS and OS by multivariate analysis. In subgroup analysis by baseline characteristics, we could not find any group with benefit of adjuvant chemotherapy. Conclusions: AC did not improve DFS and OS of patients with ypT0-3N0 rectal cancer after neoadjuvant CRT followed by TME. The role of AC in LARC with ypT0-3N0 after preoperative CRT should be evaluated in prospective randomized trials with larger sample size.
Is metronomic cyclophosphamide (mCTX) a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) in the era of new agents (NAs)? A retrospective multicenter Italian study.
Authors: Orazio Caffo, Ugo De Giorgi, Francesco Ferraú, Maddalena Donini, Gaetano Facchini, Marco Maruzzo, Marcello Tucci, Vincenza Conteduca, Francesca Maines, Lorena Rossi, Antonello Veccia, Enzo Galligioni
Journal: Journal of Clinical Oncology (2016)

326 Background: Several NAs, such as abiraterone acetate (AA), cabazitaxel (CABA), and enzalutamide (ENZ), are able to significantly prolong mCRPC pts survival after docetaxel (DOC) failure. Nevertheless, all pts eventually show progressive disease with NAs and several pts may require further treatment. mCTX was considered as a feasible and tolerable therapeutic option after DOC failure before the introduction of NAs in the clinical practice. The present retrospective study describes the clinical outcomes of mCTX, used in mCRPC pts after the failure of both DOC and at least one NA. Methods: We retrospectively reviewed the clinical records of all mCRPC pts treated in 8 Italian hospitals after the introduction of NAs in the clinical practice. We considered as eligible for the present analysis all pts who received mCTX after DOC and at least one NA. All pts were treated with CTX 50 mg po daily until disease progression. Results: From December 2011 to June 2015, a consecutive series of 48 mCRPC pts, median age 72 yrs (56-90), with bone (94%), nodal (67%) or visceral (25%) mets, was treated with mCTX. All pts have previously received a DOC-based chemotherapy followed by only one NA in 21 cases, two NAs in 20, and all three NAs in 7. The median duration of the treatment was 10.4 wks (range 3.6-61.1). Recorded grade 3-4 toxicities were: anemia (5 pts), leucopenia (1), thrombocytopenia (2), fatigue (2), and anorexia (1). Seven pts (14%) achieved a PSA reduction ≥ 50% and 2 (4%) an objective response. The median progression free survival (PFS) was 3.5 mos with 7 pts (14%) showing a PFS ≥ 9 mos. The median overall survival was 6.9 mos. Conclusions: In our experience, mCTX was a feasible and well tolerated therapeutic option in heavily pre-treated pts with very advanced mCRPC. Despite its activity was limited, the clinical outcomes of this cheap treatment are similar to those observed with NAs administered in third/fourth line with a quote of pts experiencing a prolonged disease control. Prospective studies are needed to define the therapeutic role of mCTX after NAs in mCRPC pts.
Surgery in patients with metastatic colorectal cancer in western Europe.
Authors: Z. Zhao, E. M. Pelletier, B. Barber, M. Bhosle, S. Wang, D. Klingman, S. K. Gao
Journal: Journal of Clinical Oncology (2011)

e16529 Background: The objective of the study was to assess the rates of cancer-related surgery in patients with metastatic colorectal cancer (mCRC) following mCRC diagnosis in clinical practice in five European countries. Methods: This cohort study used the LifeLink Oncology Analyzer Database from IMS Health for patients with mCRC from five European countries (France, Germany, Italy, Spain and the United Kingdom [UK]). The database included full treatment history from diagnosis to current treatment, including cancer-related surgical procedures. All patients aged ≥21 years at mCRC diagnosis and with data collected during 2009 were included. Surgical procedures were examined descriptively by the purpose and location of surgery. Results: The study sample included 3249 patients with mCRC; 515, 862, 656, 649 and 567 were from France, Germany, Italy, Spain and the UK, respectively. Following mCRC diagnosis, at least one cancer-related surgical procedure for any purpose was seen in 30.5% (UK), 35.2% (Germany), 35.6% (Spain), 36.3% (France),and 38.4% (Italy) of patients, with a mean of 1.3 (UK) to 1.6 (France) procedures. The rate of surgery for curative purposes was the highest in Italy (13.4%), followed by France (12.8%), Spain (10.3%), Germany (9.2%), and was the lowest in the UK (7.2%). Surgery performed on the primary tumour (12.4-27.1% of patients, depending on the country) and on the metastatic sites (6.4-14.6%) made up the majority of all surgical procedures. Conclusions: Cancer-related surgery is highly prevalent during the treatment of mCRC, suggesting an important role in meeting the goals of mCRC treatment. The role of pharmacological treatment options and their potential to interfere with both surgery use and surgical outcomes should be considered when evaluating mCRC treatment strategies.
Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancer
Authors: Y. L. Tham, C. Gutierrez, H. Weiss, S. Mohsin, S. Hilsenbeck, R. Elledge, G. Chamness, C. K. Osborne, D. C. Allred, J. C. Chang
Journal: Journal of Clinical Oncology (2005)

780 Background: Studies have shown that taxanes have improved clinical outcome and survival. The goal of this study was to define the clinical efficacy of docetaxel in treatment-naïve large locally advanced breast cancers. Clinical and pathological responses were evaluated, and changes in biomarkers by immunohistochemistry (IHC) were assessed to better understand docetaxel’s mechanism of action. Methods: 48 patients were enrolled. Patients received 4 cycles of docetaxel (100mg/m2 q3weeks) followed by surgery and 4 cycles of doxorubicin and cyclophosphamide (60/600 mg/m2 q3weeks). Radiation and hormonal therapy were given if clinically indicated. Clinical responses were assessed at completion of neoadjuvant docetaxel. Pathological responses were considered complete (pCR) if no tumor cells were identified in the surgical specimen or near complete (npCR) if only occasional scattered tumor cells were seen. Proliferation (Ki67) and apoptosis (cleaved caspase-3) were measured by IHC at baseline and in the surgical specimens. Results: The median tumor size was 9 cm (range 4–36 cm). Response rate was 75% with clinical complete response in 27%, partial response in 48%, and stable disease in 25% of patients. pCR/npCR was reported in 20% of patients. With a median follow up of 28 months, 89% and 71% of the patients were disease-free at 12 and 24 months, respectively. Overall survival at 24 months was significantly improved in patients who achieved a clinical response, 85% vs. 51%, p=0.008, but pCR/npCR was not a significant predictor of outcome. Apoptosis was induced in clinical responders (change from 2.6% to 3.8%, p=0.002), while the proliferation index did not change significantly. In patients who had no clinical response to docetaxel, neither apoptosis nor proliferation changed significantly. Conclusion: Neoadjuvant single agent docetaxel is effective in treating patients with large locally advanced breast cancer, giving durable clinical and pathological responses, and good survival outcome in patients with clinical responses. Docetaxel appears to primarily affect apoptosis in responders. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Definitive radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer: A retrospective analysis.
Authors: Akira Nakamura, Keiko Shibuya, Kyoichi Takaori, Yoshiya Kawaguchi, Michio Yoshimura, Yukinori Matsuo, Satoshi Itasaka, Masahiro Hiraoka
Journal: Journal of Clinical Oncology (2012)

366 Background: Only surgical resection can provide a chance of long-term survival for patients with pancreatic cancer, but loco-regional recurrence has been a major challenge which inevitably results in poor prognosis and loss of patients’ quality of life. Curative reoperation is seldom attainable but has been suggested to have benefits on overall survival. We hypothesized that definitive radiotherapy could offer a good control for the unresectable local recurrence and improve survival. The primary objective of this retrospective analysis is to evaluate the efficacy and tolerability of definitive radiotherapy for patients with isolated locally-recurrent pancreatic cancer. Methods: A total of 26 patients, who developed local recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2011, were retrospectively analyzed. The isolated local recurrence was diagnosed with the radiological images (CT/MRI/PET) and tumor marker relapse. The overall survival (OS) and local control rate (LC) were calculated from the start day of radiotherapy and estimated by Kaplan-Meier method. The responses in tumor size and tumor markers were evaluated. The treatment-related toxicity was assessed according to CTC-AE (ver. 4.0). Results: The median total dose of radiotherapy was 50.4 Gy (range, 39.6–54 Gy). Concurrent chemotherapy consisted of gemcitabine (62%), S-1 (19%), and 5-fluorouracil (4%). At a median follow-up time of 13 months, the 1-year OS and median survival were 75% and 21.6 months, respectively. The 1-year local control rate was 59%. Objective radiological response was not seen. The tumor marker reduction and ≥ 50% reduction were observed in 65% and 12%. Grade≥3 hematological toxicity was seen in 62%. Grade ≥ 3 of acute gastrointestinal toxicity was not observed. At a late phase, Grade 3 ileus observed in one, and Grade 3 gastric bleeding ulcer was seen in one patient. Conclusions: Definitive radiotherapy resulted in encouraging local control and overall survival for patients with isolated locally-recurrent pancreatic cancer. This treatment strategy should be further evaluated prospectively.
The impact of guideline treatment nonadherence on survival for colorectal cancer patients: Propensity score calibration via a validation cohort.
Authors: Robert Brooks Hines, Sue Min Lai, Joaquina Celebre Baranda, Kimberly K. Engelman, Frank Dong, A. Rana Bayakly, Tracie Collins
Journal: Journal of Clinical Oncology (2016)

308 Background: The quality of cancer care has been the focus of ongoing concern for cancer researchers, providers, and policy makers. The objectives of this study were: 1) to evaluate nonadherence with National Comprehensive Cancer Network treatment guidelines for colorectal cancer (CRC) patients and the impact on survival, and 2) to obtain error-corrected estimates of effect by means of propensity score calibration via a validation cohort. Methods: CRC patients identified by the Georgia Comprehensive Cancer Registry for the years 2000-07 were eligible (N = 18,388). Naïve propensity score (PS n ) adjustment and PS calibration (PSC) via a validation cohort were utilized to obtain hazard ratio estimates for the impact of guideline treatment nonadherence on 5-year overall survival. The validation cohort contained additional information on comorbidity and payer status which was used to obtain error-corrected estimates of effect by PSC. Results: Treatment nonadherence conferred a large increased risk of death early in the follow-up period which declined over time (Table 1). Comparison of results from the PS n and PSC models indicated moderate to large bias due to unmeasured confounding in the PS n model (data not shown). Conclusions: PSC produced attenuated estimates and had an impact on study conclusions in the latter follow-up period. For CRC patients, health services research into the quality of care received by cancer patients is necessary to continue the improving trend in CRC-related mortality. [Table: see text]
The CAIRO4 study: The role of surgery of the primary tumour with few or absent symptoms in patients with synchronous unresectable metastases of colorectal cancer—A randomized phase III study of the Dutch Colorectal Cancer Group (DCCG).
Authors: Johannes H.W. de Wilt, Cornelis Verhoef, Cornelis J. A. Punt, Jorine HW 't Lam-Boer, Mette Yilmaz, Linda Mol, Miriam Koopman
Journal: Journal of Clinical Oncology (2016)

TPS782 Background: There is no consensus regarding resection of the primary tumour with few or absent symptoms in patients with synchronous unresectable metastatic colorectal cancer. A potential benefit of resection of the primary tumour is to prevent complications of the primary tumour in later stages of the disease. Retrospective studies also show a potential survival benefit for patients undergoing resection. However, surgery can cause severe morbidity and mortality in this patient group. We hereby propose a randomized trial in order to demonstrate that resection of the primary tumour improves overall survival. Methods: The CAIRO4 study is a multicentre, randomized, phase III study of the Dutch Colorectal Cancer Group (DCCG). Patients with synchronous unresectable metastases of colorectal cancer and few or absent symptoms of the primary tumour are randomized 1:1 between systemic therapy only, and resection of the primary tumour followed by systemic therapy. Patients will be stratified according to location of the primary tumour (colon versus rectum), WHO performance status (0-1 versus 2), hospital of inclusion, serum LDH (normal versus abnormal) and number of metastatic sites (single versus multiple). To demonstrate a survival benefit of 6 months in the experimental arm, a total of 218 events are needed (80% power, significance lever 0.05). Accounting for accrual time and follow-up, we need a total of 360 patients (180 patients per arm). Systemic therapy will consist of fluoropyrimidine-based chemotherapy in combination with bevacizumab. The primary objective of this study is to determine the clinical benefit in terms of overall survival of initial resection of the primary tumour. Secondary endpoints include progression free survival, surgical morbidity, quality of life and the number of patients requiring resection of the primary tumour in the control arm. Accrual has started in September 2012. As of January 2015, 64 centres in the Netherlands and Denmark are participating in the CAIRO4 study. Clinical trial information: NCT01606098.
Genomic evolution in total therapy 2 (TT2) and total therapy 3 (TT3) for newly diagnosed multiple myeloma (MM): Comparison of baseline (BL) and relapse (REL) gene expression profiling (GEP) signatures.
Authors: A. Hoering, J. D. Shaughnessy, J. Haessler, R. Sexton, F. Van Rhee, Y. Alsayed, S. Waheed, B. P. Nair, J. Crowley, B. Barlogie
Journal: Journal of Clinical Oncology (2010)

8120 Background: Little is known about the genomic progression in MM. GEP provides the most comprehensive insight into global gene expression. With access to BL and REL MM samples in TT2 and TT3, we are reporting on changes occurring from BL to REL. Methods: From our data base, 128 patients were identified who had paired BL-REL samples, 76 from TT2 and 52 from TT3 and TT3-like regimens. GEP information included 70-gene model-based risk status (low/high) and risk scores (RS), molecular subgroup designation (MOL) as well as amp1q21, del1p and delTP53. Results: 61 patients retained low-risk with a median RS increase from -0.27 to 0.01; 26 moved from low- to high-risk with a median RS increase from 0.29 to 1.11; 7 switched from high- to low-risk with a median RS decrease from 1.12 to 0.47; and 34 remained high-risk with a median RS increase from 1.14 to 1.57. MOL status remained stable in 93 (74%); a switch to PR occurred in 22 from CD-1 (5), HY (6), MY (7), MS (2) and 1 each from LB and MF. Amp1q21 was acquired in 15 patients from a BL of 60, of which 6 normalized at REL; delTP53, present in 15 at BL, normalized in 14 at REL and was acquired in 16 of 106 normal cases at REL. Post-relapse survival (PRS) was superior among the 72 retaining low-risk with a median PRS of almost 5yr versus ∼1yr in the remainder (p<0.0001). Conclusions: RS increased in most cases at REL, resulting in high-risk switch from low-risk in 20% and a MOL switch to PR in 17%, with amp1q21 acquisition in 11%. PRS was favorably affected when low-risk status was retained with a median of ∼5yr versus ∼1yr in the remainder. No significant financial relationships to disclose.
Predicting pathologic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer using FDG PET/CT.
Authors: S. Shanmugan, R. Arrangoiz, J. R. Nitzkorski, J. Q. Yu, T. Li, A. A. Konski, J. M. Farma, E. R. Sigurdson
Journal: Journal of Clinical Oncology (2011)

505 Background: Pathologic complete response (pCR) after neoadjuvant chemoradiation has been observed in 15% to 30% of patients with locally advanced rectal cancer. The utility of FDG PET/CT scans in the management of patients with stage II or III rectal cancer is not well defined. The objective of this study is to determine if FDG PET/CT can be used to predict pCR and disease-free survival in patients receiving neoadjuvant chemoradiation with locally advanced rectal cancer. Methods: A retrospective chart review was conducted in patients with endorectal ultrasound-staged T3 to T4 rectal tumors who underwent preoperative and postoperative FGD PET/CT imaging. All patients were treated with neoadjuvant chemoradiotherapy (CRT). Maximum standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, % SUV change, and time between therapy and surgery in comparison to pathological complete response. Kaplan-Meier estimation was used to look for significant predictors of survival. Results: Seventy patients (mean age 62; 42M:28F) with preoperative stage T3Nx (n = 60) and T4Nx (n = 10) underwent pre-CRT and post-CRT FDG PET/CT scans between November 2002 and March 2009. All patients underwent definitive surgery after therapy with standard pathologic evaluation.The pCR rate was 26%. Median pre-CRT SUV was 10.5 while the median post-CRT SUV was 4.05. Patients with pCR had a lower mean post-CRT SUV compared to those without pCR (2.7 vs. 4.5, p = 0.02). Median SUV decrease was 61% (range 6% to 95%) and was significant in predicting pCR (p = 0.004). Patients with a pCR had a greater time interval between neoadjuvant therapy and surgery (median 57 days vs. 50 days) than those without (p = 0.05). Furthermore, patients with post-CRT SUV &lt; 4 had a lower local recurrence rate compared to those with post-CRT SUV &gt; 4 (p = 0.03). Patients with SUV decrease &gt; 61% had improved overall survival at mean follow-up of 39 months than those without (p = 0.01). Conclusions: PET/CT can predict response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Pre-CRT SUV was the only predictor of disease-free survival. No significant financial relationships to disclose.