tbuckley/cabot-search huggingface dataset:
Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2–Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial
Authors: Amir Sonnenblick, Dominique Agbor-Tarh, Ian Bradbury, Serena Di Cosimo, Hatem A. Azim, Debora Fumagalli, Severine Sarp, Antonio C. Wolff, Michael Andersson, Judith Kroep, Tanja Cufer, Sergio D. Simon, Pamela Salman, Masakazu Toi, Lyndsay Harris, Julie Gralow, Maccon Keane, Alvaro Moreno-Aspitia, Martine Piccart-Gebhart, Evandro de Azambuja
Journal: Journal of Clinical Oncology (2017)

Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this association in human epidermal growth factor receptor 2 (HER2 ) -positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination. In this substudy, we evaluated whether patients with diabetes at study entry-with or without metformin treatment-were associated with different disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) compared with patients without diabetes. Results A total of 8,381 patients were included in the current analysis: 7,935 patients (94.7%) had no history of diabetes at diagnosis, 186 patients (2.2%) had diabetes with no metformin treatment, and 260 patients (3.1%) were diabetic and had been treated with metformin. Median follow-up was 4.5 years (0.16 to 6.31 years), at which 1,205 (14.38%), 929 (11.08%), and 528 (6.3%) patients experienced DFS, DDFS, and OS events, respectively. Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio [HR], 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004). This effect was limited to hormone receptor-positive patients. Whereas insulin treatment was associated with a detrimental effect, metformin had a salutary effect in patients with diabetes who had HER2-positive and hormone receptor-positive breast cancer. Conclusion Metformin may improve the worse prognosis that is associated with diabetes and insulin treatment, mainly in patients with primary HER2-positive and hormone receptor-positive breast cancer.
Does aggressive local treatment have an impact on survival in children with metastatic rhabdomyosarcoma?
Authors: Myriam Weyl Ben Arush, Veronique Minard-Colin, Veronique Mosseri, Anne Sophie Desfachelles, Christophe Bergeron, Nicole Algret, Sylvie Fassola, Nicolas Andre, Estelle Thebaud, Nadege Corradini, Valérie Bernier, Helene Martelli, Dominique Ranchere-Vince, Daniel Orbach
Journal: Journal of Clinical Oncology (2015)

10540 Background: Due to the extensive initial distant tumour spread in metastatic rhabdomyosarcoma, the importance of local treatment is sometimes underestimated. A retrospective study was conducted to identify the prognostic value of aggressive local treatment in paediatric metastatic rhabdomyosarcoma. Methods: Patients with metastatic rhabdomyosarcoma age 1 to 21 treated in France from 1998 to 2011 according to European protocols MMT-4-89, 4-91, 98 and recent national guidelines were selected. Survival comparison were performed between patients with “aggressive local treatment” (surgery and radiotherapy) and exclusive surgery or radiotherapy, after exclusion of patients with early progression. Endpoints were event-free and overall survival (OS). Results: A total of 101 children, median age 9 years, with majority of primaries in unfavourable sites (73 patients, pts), T2 tumours (66 pts), alveolar subtypes (65 pts) and large tumours (> 5cm, 83 pts) received various chemotherapy regimens. On univariate and multivariate analysis, OS was better after “aggressive local treatment” (49 pts; 44.3 ± 8%), than after exclusive surgery (10 pts; 18.8% ± 15.5%) or exclusive radiotherapy (29 pts; 16.1 ± 7.2%, P < 0.006). Moreover, OS was better in the case of surgery with complete resection (41.1 ± 10.2%) or microscopic residue (56.4 ± 14.9%) than macroscopic residue (20.0 ± 12.6%; P < 0.03). Conclusions: In this large retrospective analysis, OS appeared to be better for patients receiving “aggressive local treatment” even after adjustment for the initial patient and tumour characteristics. Isolated debulking surgery is associated with a very poor outcome and should be avoided. Aggressive local treatment in patients with rhabdomyosarcoma, even with metastasis, should be seriously considered.
The International Watch &amp; Wait database (IWWD) for rectal cancer: An update.
Authors: Maxime van der Valk
Journal: Journal of Clinical Oncology (2017)

521 Background: In 2014 the IWWD was established by EURECCA and the Champalimaud Foundation. The main goal of this database is to collect all available data to expand knowledge on the benefits, risks and oncological safety of organ preserving strategies in rectal cancer. In April 2015 the database was opened for data registration. Methods: An international multicentre observational study. Data was collected by participating centres and stored in a highly secured NEN7510 certified and encrypted research data server. Each centre always retains full ownership of their data. Results: In August 2016 the database included 775 patients from 11 countries and 35 participating institutes. 90% of all patients were included because of a clinical complete response (n = 679). All other reasons for a watch-and-wait regimen were excluded for the present analyses. As shown in table 1, imaging modalities used to assess response after induction therapy were variable. Induction treatment consisted of chemo-radiotherapy in 90% of cases. Median follow-up time is 2.6 years (range 0-24 years). Local regrowth occurred in 25% (n = 167) of all patients, of which 84% in the first 2 years of follow-up. A local regrowth was located endoluminal in 96% (n = 161) and in the loco-regional lymph nodes in 4% (n = 7). Distant metastasis occurred in 7% (n = 49). The overall 3 year-survival of all patients was 91% and for patients with a local regrowth this was 87%. Conclusions: This is the largest series of patients with rectal cancer in which surgery was omitted after induction therapy. These data illustrate differences in induction therapy as well as imaging strategies and provide some crude outcome data. Further data collection on the Watch-and-Wait strategy for rectal cancer is needed to increase knowledge on oncological safety of omitting surgery. This may contribute to international consensus on staging, treatment and surveillance guidelines in rectal cancer care. [Table: see text]
Quality improvement: An assessment of participation of medical oncologists.
Authors: Charles Henry Lim, Matthew C. Cheung, Bryan Franco, Laavanya Dharmakulaseelan, Evan Chong, Amesha Iyngarathasan, Simron Singh
Journal: Journal of Clinical Oncology (2014)

e17615 Background: Quality improvement (QI) is an essential component of oncology care. Many QI studies in surgical oncology are published, however few QI studies involving medical oncology patients are published. Our objectives were to study the attitudes of Canadian medical oncologists towards QI and to determine causes for the low publication rate of QI in the medical oncology literature. Methods: We distributed a 13 question online survey using a modified Dillman method in October 2013 to members of the Canadian Association of Medical Oncologists (CAMO) asking about attitudes towards QI, involvement in QI initiatives and barriers to QI involvement and publication. QI initiatives were defined based on criteria from the Journal of the American Medical Association in 2000. Results: We attained a 43% response rate (143/332) with 97% (138) of oncologists agreeing that QI was an important aspect of their practice, though only 49% (70) had participated in QI in the past 5 years. There were no significant differences between QI participants compared by institution type (academic vs. community). Administrators were more likely to be involved in QI than clinicians or researchers (p=0.008). Most QI participants focused on domains of safety (70%), patient-centeredness (67%) and efficiency of care (56%). Among QI participants, 72% did not publish their findings due to lack of time (34%), no identifiable journals (14%), and unfamiliarity with QI methodology (10%). Barriers to involvement in QI initiatives included uncertainty about how to get involved (45%), lack of interest (25%), and limited institutional support or recognition (12%). QI participants were more likely to be aware of recent practice changing QI publications than non-participants (p=0.003). Conclusions: Canadian medical oncologists agree that QI plays an important clinical role. However, their participation in QI initiatives and the ability to publish their work is limited by lack of knowledge about ongoing initiatives, lack of resources to aid publication, and lack of time. Improving networking opportunities and collaboration between QI clinicians, increasing awareness of QI initiatives, and rewarding QI involvement at an institutional level can help address this need.
Comparison of four different strategies of stem cell mobilization in patients with multiple myeloma.
Authors: Jeffrey Michael Sivik, Sesilya Whaley, Joseph Mierski, William J. Castellani, Mitzi Lowe, Junjia Zhu, Melissa George, Witold B. Rybka, Giampaolo Talamo
Journal: Journal of Clinical Oncology (2013)

7039 Background: There is no consensus among institutions for the optimal strategy of peripheral blood stem cell (PBSC) collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Methods: We retrospectively analysed the outcomes of PSBC collection in MM patients using the following mobilization regimens: cyclophosphamide 5,000 mg/m 2 + etoposide 1,000 mg/m 2 + G-CSF 5 mcg/Kg/day (Group A, n = 49); cyclophosphamide 2,000-3,000 mg/m 2 + G-CSF 5 mcg/Kg/day (Group B, n = 25); G-CSF 16 mcg/Kg/day (Group C, n = 21); G-CSF 16 mcg/kg/day + plerixafor 0.24 mg/Kg (Group D, n = 128). Results: The median number of PBSC collected was 28.1 (range, 2.1-134), 4.5 (0.1-39.7), 4.0 (0-7.3) and 8.4 (0.2-41.2) million CD34+/kg in groups A, B, C and D, respectively (p &lt;0.001). The mean number of collection days was 1.3, 2.2, 2.4, and 1.3 in groups A, B, C, and D, respectively (p &lt;0.001). Febrile neutropenia occurred in 16 (32.7%), 1 (4%), 0, and 0 patients in groups A, B, C, and D, respectively. One patient who received CTX 3 g/m 2 died of septic shock during the neutropenic phase. Failure to collect PBSC, defined as &lt;2x10 6 CD34+ cells/Kg for a planned single ASCT or &lt;4x10 6 for planned tandem ASCTs, was observed in 2/49 (4%), 5/25 (20%), 4/21 (19%), and 9/128 (7%) patients in groups A, B, C, and D respectively (p=0.037). Conclusions: Plerixafor + G-CSF provided the greatest benefit to risk ratio for PSBC collection in MM patients.
Tivantinib plus erlotinib versus placebo plus erlotinib in Asian patients with previously treated nonsquamous NSCLC with wild-type <i>EGFR:</i> First report of a phase III ATTENTION trial.
Authors: Koichi Azuma, Hiroshige Yoshioka, Nobuyuki Yamamoto, Toshiaki Takahashi, Makoto Nishio, Nobuyuki Katakami, Myung-Ju Ahn, Tomonori Hirashima, Makoto Maemondo, Sang-We Kim, Masayoshi Noshiro, Shiro Akinaga, Keunchil Park, Chun-Ming Tsai, Tomohide Tamura, Tetsuya Mitsudomi, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2014)

8044 Background: A randomized phase II study suggested that adding a c-Met inhibitor tivantinib (T) to an EGFR-TKI erlotinib (E) may prolong PFS in non-squamous NSCLC patients (pts) with 1-2 prior chemotherapy. Furthermore, the subset analysis suggested that survival benefit was more prominent in pts with wild-type EGFR (WT-EGFR) than in those with EGFR mutation. Therefore we conducted the phase III ATTENTION trial to compare overall survival (OS) between T+E vs. placebo (P)+E, in Asian pts with pretreated NSCLC with WT-EGFR. Methods: Four-hundred-and sixty Asian (Japan, Korea, and Taiwan) pts who had been treated with 1-2 chemotherapy for non-squamous NSCLC with WT-EGFR were planned to be randomized between T+E and P+E. The doses of T were 360mg BID and 240mg BID, for CYP2C19 extensive metabolizers (EM) and poor metabolizers (PM), respectively, whereas that of E was 150 mg QD for both EM and PM. The primary endpoint was OS, and secondary endpoints included PFS, ORR, and safety. Exploratory analysis tested biomarkers including c-Met expression and KRAS mutation. Results: New enrollment was stopped when 307 pts had been randomized, following the Safety Review Committee's recommendation based on an observed imbalance in interstitial lung disease (ILD) between the groups. Accordingly,153 and 154 pts were treated with T+E and P+E, respectively. Patient backgrounds including CYP2C19 genotype were well balanced. Results are summarized below. Typical ≥Gr.3 adverse events in T+E were anemia (13.2 %), neutropenia (10.5 %), and leukopenia (6.6 %). Fourteen pts (including 3 deaths) and 6 pts (0 deaths) developed ILD in T+E and P+E, respectively. Conclusions: Although this trial lacked a statistical power due to the prematurely termination owing to toxicity concern, our results indicated some sign for benefit for adding T to E in this population. OS was numerically prolonged but this did not reach statistical significance. Exploratory biomarker analysis may identify subsets in which benefit and risk from this treatment is well balanced. Clinical trial information: NCT01377376. Median OS Median PFS ORR T+E 12.9 mo 2.9 mo 8.4% P+E 11.2 mo 2.0 mo 6.5% HR 0.891 0.719 P value 0.427 0.019
Lymph node metastasis in gastric cancer: Location of positive station to predict survival after preoperative therapy.
Authors: Naruhiko Ikoma, Jeannelyn Estrella, Mariela A. Blum Murphy, Hsiang-Chun Chen, Xuemei Wang, Keith F. Fournier, Paul F. Mansfield, Jaffer A. Ajani, Brian D. Badgwell
Journal: Journal of Clinical Oncology (2017)

166 Background: We sought to determine the association between the identification of positive lymph nodes on D2 lymph node dissection (LND) with stage and outcomes, in the era of preoperative treatment for gastric cancer. Methods: We reviewed data from a prospectively maintained database of gastric cancer patients who underwent resection of gastric or gastroesophageal cancer at our institution from 2005-2016. Central lymph nodes (CnLN) were defined as common hepatic, celiac, and proximal splenic artery lymph nodes (stations #8, 9, and 11p). Risk factors for CnLN metastases, and overall survival (OS) were examined. Results: We identified 356 patients, median age was 64 years (IQR 54-71) and 59% were male. Preoperative therapy was given in 66% of patients. D2 LND was performed in 80% of patients, and the median number of LN examined was 25 (IQR 18-34). Most patients (N = 244, 68%) had separately-examined CnLN in pathology and the median number of examined LNs was higher in this group (27 vs 19; p &lt; 0.001). The CnLN positivity rate was 9.1% (22/244; #8: 4.8%, #9: 6.1%, and #11p: 4.8%), which was higher in advanced pT stage patients (pT0 - 3%, pT1 - 0%, pT2 - 6%, pT3 - 18%, pT4 - 13%; p = 0.001). If we assume that D2 LND was not performed on these patients, a total of 7 (3%, 7/244) patients would have had pN stage down-migration (6 with N1 to N0, 1 with N2 to N1). Of the 22 CnLN-positive patients, 10 (45%) had pN1, 2 (9%) had pN2, and 10 (45%) had pN3 stages. On multivariate analysis, EUS N stage (positive) was associated with positive CnLNs (OR 2.86 [95%CI 1.08-7.58]). Among 342 patients who had R0 resection, the median follow-up was 3.6 years, and the median OS was 11.6 years. Among patients who received preoperative therapy, pT3/4 stage (HR 2.44 [1.27-4.69]; p = 0.01) and positive CnLN (HR 5.44 [2.36-12.52]; p &lt; 0.001) were negatively associated with OS by multivariate analysis. Conclusions: CnLN metastases are uncommon in gastric cancer, and are associated with an adverse impact on OS. However, long-term survival is still possible in patients with positive CnLN whom underwent a D2 lymph node dissection. Larger multi-institutional studies are needed to determine if CnLN positivity requires a separate staging category.
A phase II clinical trial of ganetespib (STA-9090) in previously treated patients with advanced esophagogastric cancers.
Authors: Eunice Lee Kwak, Lipika Goyal, Thomas Adam Abrams, Amanda Carpenter, Brian M. Wolpin, Raymond Couric Wadlow, Jill N. Allen, Rebecca Suk Heist, Nadine Jackson McCleary, Jennifer A. Chan, Wolfram Goessling, Deborah Schrag, Colleen Evans, Kimmie Ng, Peter C. Enzinger, David P. Ryan
Journal: Journal of Clinical Oncology (2013)

4090 Background: Subsets of esophagogastric (EG) cancers harbor genetic abnormalities, including amplification of HER2 or MET, or mutations in PIK3CA, EGFR, or BRAF. These genes encode clients of the molecular chaperone heat-shock protein 90 (HSP90), and inhibition of HSP90 may promote the degradation of these oncogenic signaling proteins. Ganetespib is a novel triazolone heterocyclic inhibitor of HSP90 that is a biologically rational treatment strategy for advanced EG cancers. Methods: This was a multicenter, single-arm Phase 2 trial. Eligibility: Histologically confirmed advanced EG cancer; progression on ≤ 2 lines of systemic therapy; ECOG PS 0-1. Treatment: Ganetespib 200mg/m 2 IV on Days 1, 8, and 15 of a 28-day cycle. Primary endpoint: overall response rate (ORR). Results: 26/28 patients enrolled received ≥ 1 dose of drug. The characteristics of the 26 patients were: male 77%, median age 64 years old; ECOG PS 0/1 42/58%; median number of prior therapies 2; esophageal/GEJ/gastric 27/42/31%; prior platinum 92%, prior fluoropyrimidine 88%, prior taxane 38%, prior trastuzumab 15%. Median follow-up was 83 days. The most common drug-related adverse events were: diarrhea (77%), fatigue (65%), elevated ALKP (42%), and elevated AST (38%). The most common Grade 3/4 AEs included: leucopenia (12%), fatigue (12%), diarrhea (8%), and elevated ALKP (8%). 14/26 required ≥ 1 dose modification. 22/26 patients completed at least 2 cycles of ganetespib and were evaluable for response. One complete response was seen, and this patient continues on treatment as of cycle 31 (27.5 mos). Molecular characterization of this patient’s tumor revealed a KRAS mutation in codon 12. The ORR was 1/26 (4%). Two of six patients with HER2-positive disease achieved 12% and 19% tumor reduction from baseline, respectively. TTP was 48 days (1.6 mos) and OS was 83 days (2.8 mos). Conclusions: Ganetespib showed manageable toxicity. While the study was terminated early due to insufficient evidence of single agent activity, the durable CR and 2 minor responses suggest that there may be a subset of EG patients who could benefit from this drug. The molecular determinants of response, however, have yet to be fully characterized. Clinical trial information: CT01167114.
Phase II trial of weekly docetaxel and capecitabine in advanced renal cell carcinoma
Authors: U. N. Vaishampayan, L. K. Heilbrun, J. Eliason, E. Pontes, J. Forman, M. Cher
Journal: Journal of Clinical Oncology (2004)

4672 Background: Renal cancer overexpresses thymidine phosphorylase (TP), the rate limiting enzyme converting capecitabine to 5-fluorouracil. Docetaxel increases the levels of TP and hence would enhance effects of capecitabine. The combination of capecitabine and docetaxel has demonstrated preclinical and clinical synergy. Based on this, a phase II study is being conducted, evaluating efficacy and toxicity in metastatic renal cancer. Methods: Docetaxel is administered at a dose of 36mg/m2 weekly on days 1, 8 and 15 of a 28 day cycle. The capecitabine is administered orally at a dose of 1250 mg/m2/day in two divided doses from days 5 to 18. Toxicity is assessed every week on days of docetaxel therapy and response is assessed every 2 cycles. Eligibility includes adequate organ function, metastatic renal cancer and adequate renal,liver and marrow function. Dose adjustments for toxicity are performed. Correlative studies of serum TP and dihydropyrimidine levels pre and post therapy are being conducted. Results: Seventeen patients have been enrolled to this ongoing trial. Patient characteristics include: median age 61 years (range 50–80 years), 5 are African American,14 with clear cell histology, 14 with visceral and bone metastases, 12 with nephrectomy and 7(41%) with performance status of 2. 9 patients had failed prior immunotherapy of which 6 received high dose interleukin-2. 45 cycles have been delivered to date with 6 patients requiring dose reductions. The regimen was very well tolerated even in the elderly patients. 2 treatment related hospitalizations occurred; one for febrile neutropenia and one for diarrhea and dehydration. There were no treatment related deaths. The other severe toxicities were grade 3 diarrhea and anemia in 3 patients. Fifteen patients are evaluable for response of which six continue on therapy. One partial response has been observed to date. Six patients have stable disease. Conclusions: Capecitabine and docetaxel demonstrates preliminary efficacy in metastatic renal cancer. The favorable toxicity profile even in patients with impaired performance status makes this a universally applicable regimen. Supported in part by Aventis Inc. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Contents, Vol. 54, 1990
Authors: Ratnin Dewaraja, Yuji Sasaki, Antoinette Ambrosino Wyszynski, Tuula Pahkinen, Anja Cabble, Reinhard Liedtke, Isao Fukunishi, Isao Fukunishi, Geir Nielsen
Journal: Psychotherapy and Psychosomatics (1990)
Systemic therapy and overall survival trends in patients with non-urothelial histologic variants of muscle invasive bladder cancer undergoing radical cystectomy.
Authors: Shreyas Joshi, Elizabeth Handorf, Andres Correa, Alexander Kutikov, Benjamin T. Ristau, Miki Haifler, Rosalia Viterbo, Richard E. Greenberg, David Chen, Robert G. Uzzo, Daniel M. Geynisman, Marc C. Smaldone
Journal: Journal of Clinical Oncology (2017)

376 Background: Histological variants of urothelial carcinoma (UC) of the bladder have a poorer prognosis than histologically pure UC, and the role of neoadjuvant chemotherapy (NAC) in this group is unclear. Our objective was to evaluate NAC practice patterns and survival outcomes in patients with histologic variants undergoing radical cystectomy (RC). Methods: Patients with cT2-4N0-3M0 muscle invasive bladder cancer (MIBC) who underwent RC from 2003-2012 were selected from the National Cancer Database (NCDB). Patients were categorized by histology code as pure UC or histologic variants. Adjusting for patient and clinical characteristics, generalized estimating equations were used to test the association between histology and receipt of NAC. The association between receipt of NAC and overall survival (OS) was evaluated using Kaplan Meier curves and Cox regression models. Results: In 19,976 patients meeting inclusion criteria, receipt of NAC in histologic variants was less (11-14%) than in pure UC (22%), with the exception of micropapillary disease (23%) (Table). Median OS was lower in variant histologies than for pure UC (8.4 – 30.2 vs. 37.6 months). Receipt of NAC was associated with improved survival compared to RC or RC+adjuvant chemotherapy in patients with pure UC (HR 0.91, p=0.0016). There was no evidence of a survival benefit for NAC in the variant histologies, or that treatment effects differed by histology (P-val for interaction=0.84). Conclusions: In the NCDB, a substantial proportion of patients (13%) with histologic variants of MIBC undergoing RC receive NAC in the absence of a proven survival benefit. Clinical trials inclusive of patients with variant histologies are necessary to elucidate the role of NAC prior to RC. [Table: see text]