tbuckley/cabot-search huggingface dataset:
Body mass index and survival of patients with metastastic renal cell carcinoma: Data from the German prospective RCC registry.
Authors: Lothar Mueller, Peter J. Goebell, Ulla Von Verschuer, Hans-Juergen Hurtz, Melanie Franzem, Michele Vogt, Norbert Marschner
Journal: Journal of Clinical Oncology (2013)

454 Background: Being overweight is a known risk factor for developing renal cell carcinoma (RCC). On the other hand, overweight patients may harbor a less aggressive type of disease. A recent meta-analysis was able to demonstrate that a high preoperative BMI was an independent prognostic indicator for better overall survival in patients with RCC. We present data on the prognostic impact of the postoperative BMI, at the start of systemic treatment in patients with advanced or metastatic RCC (mRCC). Methods: The German RCC registry is a prospective, longitudinal, multicenter study conducted by a network of 133 office-based medical oncologists in Germany to document treatment of unselected patients with mRCC. Based on the inclusion criteria for this analyses we identified 475 prospectively documented patients who received 1 st -line systemic treatment. Patients were grouped by their BMI and overall survival was estimated by Kaplan-Meier analysis. A multivariate cox proportional hazards model was used to determine the impact of potentially prognostic variables at the start of systemic treatment (sex, age, BMI, comorbidity, Motzer’s score, tumor stage [TNMRG], and number of metastatic sites) on overall survival. Results: The mean age of patients at the start of systemic treatment was 68 years and the median follow-up was 23.8 months. 118 (25%) presented with a BMI &lt; 24, 195 (41%) with a BMI 24 - 28 and 162 (34%) with a BMI &gt; 28. Patient characteristics did not differ between groups, except more patients in the low BMI group had a higher prognostic risk according to Motzer-score (11% vs. 5 % vs. 6 %). Median overall survival was 10.0 month, 16.7 month and 23.4 month in the low, medium and high BMI group, respectively. In a multivariate analysis, BMI (HR 0.94, 95% CI 0.91-0.98, p &lt; .001) and Motzer-Score (HR 1.83, 95% CI 1.59-2.12, p &lt; .001) had a significant impact on overall survival. Conclusions: In addition to Motzer’s prognostic score, the BMI at the start of palliative treatment may be used to discriminate mRCC patients with good and poor prognosis. Patients with a higher BMI tend to live longer than patients with low or normal BMI supporting evidence from previous meta-analyses on preoperative BMI and outcome.
Synergistic effects of cabozantinib to temozolomide and bevacizumab in patients with heavily pretreated relapsed uterine leiomyosarcoma.
Authors: Sayaka Ikeda, Kazuya Kudoh, Naoki Sasaki, Masashi Takano, Tomoko Goto, Ryoko Kikuchi, Masaru Sakamoto, Tsunekazu Kita, Nobuyuki Susumu, Daisuke Aoki, Hiroko Kouta, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2015)

5590 Background: Although uterine leiomyosarcoma (ULMS) has been treated with adriamycin, dacarbazine, ifosfamide, gemcitabine, docetaxel, et al, the effect is not satisfactory. We have reported the effect of temozolomide (T) combined with bevacizumab (B) in heavily pretreated relapsed ULMS (Ref.). In this study, we evaluated the effects of addition of cabozantinib (C) to T and B. Methods: From 2009 to 2014, total 20 patients (pts) with heavily pretreated relapsed ULMS were enrolled. Fourteen of 20 pts were treated with T (80mg/body/day, 3 week one week rest) and B (2mg/kg; days 1, 8 and 15, q4 weeks) (TB, n = 14). Since 2013, C (140mg/body/week) was added to TB (TBC, n = 6). Treatment was continued until disease progression and/or unmanageable toxicities. The response and adverse effects were evaluated using the response evaluation criteria in solid tumors (RECIST), and common terminology criteria for adverse events (CTCAE) version 3.0. Results: As shown in Table, four (20%) of 20 pts had complete response (CR), four (20%) had partial response (PR) and nine (45%) had stable disease (SD) for at least three months. The response rate (RR; CR+PR) and clinical benefit rate (CBR; CR+PR+SD>3mo) were 40% and 85%, respectively. The median progression-free survival was 10.5 (3 - 44) months. Intriguingly, when added C to TB, the effect was significantly reinforced, showing that two (33%) of 6 cases had CR, and the RR and CBR was 50% and 100%, respectively. Toxicity was mild and manageable. Conclusions: Addition of C to T and B resulted in synergistic effects with mild toxicity in heavily pretreated relapsed ULMS as shown in Table. These results warrant further prospective and randomized studies. Response to TB/TBC in heavily pretreated relapsed ULMS. n CR PR SD PD RR CBR TB/TBC 20 4 4 9 3 40% 85% TB 14 2 3 6 3 35% 78% TBC 6 2 1 3 0 50% 100% Reference:Sasaki N, Takano M, Kikuchi Y, et al. Effects of temozolomide and bevacizumab in patients with pretreated relapsed uterine leiomyosarcoma. J Clin Oncol 32:5s, 2014 (suppl; abstr 5603)
Eculizumab in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Report of All 153 Patients Treated in the UK
Authors: Anita Hill, Richard J Kelly, Austin G Kulasekararaj, Shreyans A Gandhi, Lindsay D Mitchell, Modupe Elebute, Stephen John Richards, Matthew Cullen, Louise M Arnold, Joanna Large, Alexandra Wood, Gemma L Brooksbank, Tracy Downing, Claire McKinley, Dena Cohen, Walter M Gregory, Judith C. W. Marsh, Ghulam J. Mufti, Peter Hillmen
Journal: Blood (2012)
Patient-reported sleep disruption as an independent prognostic factor for overall survival in metastatic colorectal cancer.
Authors: Ayhan Ulusakarya, Oxana Palesh, Georg A. Bjarnason, Carl Deguzman, Karyn Haitz, Sylvie Giacchetti, David Spiegel, Francis Levi, Pasquale F. Innominato
Journal: Journal of Clinical Oncology (2014)

410 Background: Sleep disruption is a prevalent problem among cancer patients and survivors, but clinical correlates of poor sleep are understudied, especially in colorectal cancer. We recently showed that metastatic breast cancer patients with poor sleep efficiency have a shorter overall survival. The primary study objective is to clarify the relationship between subjective sleep disruption and survival in patients with metastatic colorectal cancer (MCC). Methods: 240 pts (63% male, mean age=59; SD=11.0) treated for MCC in 1st to 5th line of 5-fluorouracil based chemotherapy completed the QOL Questionnaire (EORTC QLQ-C30). We considered sleep to be disrupted if patients reported little to severe trouble sleeping (scores &gt;0 ). Multivariate Cox models included age, gender, site of primary tumor, stage at diagnosis, number of metastatic sites, performance status and prior chemotherapy. Results: 65.4% of the patients reported mild to severe sleep disruption according to EORTC QLQ-C30. Patients with trouble sleeping had poorer overall survival as compared to those without sleep disruption (HR: 1.47 [1.11 to 1.95]; p=0.008). Respective median survival times (months) were 14.2 [95% CI: 12.3 to 16.1] and 17.7 [10.0 to 25.3]. The survival benefit observed in patients without sleep disruption remained statistically significant after adjustment for other prognostic factors. The final multivariate prognostic model included subjective sleep disruption (HR: 1.49 [1.11 to 2.00]; p=0.009), number of metastatic sites (p&lt;0.001), performance status (p=0.023), and prior chemotherapy (p&lt;0.001). Conclusions: Our findings show that patients reported sleep disruption is an independent prognostic factor for overall survival in MCC. Future research is needed to determine the mechanisms of sleep disruption and its effect on survival, and whether treatment of sleep disruption can improve survival in MCC.
Short-term outcomes after colorectal cancer among the oldest old patients: A cross-national comparative study.
Authors: A. Syse, J. P. Bynum, H. G. Welch, S. Tretli, S. S. Soneji
Journal: Journal of Clinical Oncology (2011)

3622 Background: As populations age, more people are being diagnosed with cancer at late age. We compared outcomes after colorectal cancer (CRC) diagnosis in the oldest old patients in Norway and the US to assess factors influencing outcomes across dissimilar health care systems. Methods: We extracted all CRC patients aged 80+ diagnosed in 2004-06 from the Cancer Registry of Norway and US SEER-registries and used descriptive statistics to assess differences in national incidence (IR) and mortality (MR), treatment, and one-year case-fatality (CF). Results: Norwegian CRC IRs were higher for patients <95 years, but similar to US IRs for patients 95+. MRs increased with age but were generally higher in Norway than the US. Overall CRC CF was also markedly higher in Norway (30% vs 23%). Stage distributions differed significantly, with 39% localized cancers in the US and 21% in Norway, whereas the reverse was seen for regional cancers. Distant spread proportions were similar. Testing to determine stage was common in both countries, albeit age-dependent. No (20%), minor (6%) or large (71%) resection rates were similar. Resection type depended on both age and stage: 80% of localized cancers were resected in 80-84 olds, but decreased to around 40% for those 95+; while >85% of regional cancers were removed, irrespective of age. Large resection rates for localized cancers were similar for Norwegian and U.S. patients aged 80-89 (76% vs 79%), but more frequent in the US for the 90+ (65% vs 48%). Localized CFs were 14% in Norway vs 9% in the US, respectively. Regional and metastatic CFs were more comparable than overall CFs, but remained unfavorable for Norway. Conclusions: Favorable MR and one-year CF outcomes are observed for CRC patients over the age of 80 in the US as compared to Norway. This may reflect the different stage distribution at presentation, perhaps explained by differences in screening practices prior to diagnosis. Stage-adjusted outcomes remain favorable for U.S. patients, and may be explained by a greater use of large resections in the oldest old with localized disease. Research on the effect of past and current screening practices and surgical approaches on outcomes for CRC in the oldest old warrants further research.
Phase II: Concurrent cisplatin/radiotherapy followed by adjuvant cisplatin/docetaxel for locally advanced nasopharyngeal carcinoma
Authors: M. S. Kandil, H. S. Nasser, F. A. Ammar, S. A. Bandey, M. A. Asiri, A. M. Zahrani
Journal: Journal of Clinical Oncology (2005)

5573 Background: Concurrent cisplatin and radiotherapy as well as docetaxel/cisplatin combination are highly active agents for locally advanced nasopharyngeal cancer (LANPXCA).The efficacy and tolerability of concurrent cisplatin/radiotherapy followed by adjuvant docetaxel/cisplatin are explored in a phase II study Methods: From May 2001 to Feb 2003, 17 patients with LANPXCA stage III-IV were treated with 2 cycles of 3 weekly cisplatin 100mg/m2 concurrently with radiotherapy aiming at 70Gy Gy/ 35 fraction/ 7 weeks. Three weeks post radiotherapy 4 cycles of adjuvant 3 weekly docetaxel 60mg/m2 1 hour IV infusion D1 and cisplatin 60mg/m2 2 hours IV infusion D1 with prophylactic G-CSF support as 5μg/kg s.c. D3–5 were added. The median follow up was 30.2 months (15.6 - 41.1). Results: The median age was 50 years (25–70) and male to female ratio was 4.3:1. Nasal obstruction 82.4%, neck swelling 76.5%, headache 70.6% and impaired hearing 52.9% were the commonest symptoms. The most common histopathologic grade was G3 squamous cell carcinoma 94.1%. The majority of patients were stage IV 70.6% while 29.4% were stage III, (AJCC, 1997). Patients with G2 ECOG performance status were 47.1% while 52.9% were G1. The treatment was tolerable with the commonest G3 acute toxicities were dysphagia 23.5%, oral mucositis 11.3%, dermatitis 11.3%, leukopenia 5.9% and thrombocytopenia 5.9% while the commonest late toxicity was G2 mouth dryness in 88.2%. Complete remission was achieved in 15/17 patients (88.2%) while 2/17 (11.8%) were partial responders. Failure sites were locoregional; parapharyngeal space 5.9% and cervical nodes 5.9%. The Kaplan Meyer 41- month disease free survival was 88.2% while the 41- month overall survival was 100%. Conclusions: Concurrent cisplatin with radiotherapy followed by adjuvant docetaxel/cisplatin combination chemotherapy appears to be an effective and tolerable outpatient treatment for LANPXCA. No significant financial relationships to disclose.
Efficacy and Safety of Deferasirox (Exjade®) in Preventing Cardiac Iron Overload in β-Thalassemia Patients with Normal Baseline Cardiac Iron: Results from the Cardiac Substudy of the EPIC Trial
Authors: Dudley Pennell, Pranee Sutcharitchan, Amal El-Beshlawy, Yesim Aydinok, Ali Taher, Gillian Smith, Dany Habr, Ulrike Kriemler-Krahn, Abdel Hmissi, John B Porter
Journal: Blood (2008)
Evolution of circulating tumor cells (CTCs) during neoadjuvant treatment and radical surgery in patients (pts) with liver-only metastases of colorectal cancer (L-CRC).
Authors: L. Teijeira, A. Viúdez, V. Arrazubi, J. Verdun, M. J. Uriz, M. L. Antelo, A. Tarifa, C. Zazpe, R. Vera
Journal: Journal of Clinical Oncology (2011)

e14146 Background: The presence of baseline ≥ 3 (CTCs) in 7.5 mL of blood is predictive of a poor outcome in advanced colorectal cancer (JCO, 26;19: 3213-3221, 2008). The aim of this prospectively. study was to quantified CTCs performance during neoadjuvant treatment and before/after radical surgery in pts with L-CRC. Methods: From February 2009 to October 2010, 18 pts with L-CRC were included. Median age was 61 years old (48-79), 55.6% men. K-Ras status was: 54% wild-type; 46% mutated. 7.5 mL of blood were drawn in CellSave tubes. CTCs were isolated and enumerated at baseline, before and just performed radical liver surgery. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch System (Veridex/Immunicon Corp.). Results: Baseline determination was < 3 CTCs in 72.2 % of pts, and increased to 77.8% just before liver surgery. A slight decreased in pts with < 3 CTCs was observed after liver surgery (70.6%). Conclusions: Unlike the published data of CTCs before/after liver surgery in systemic circulation (JCO, 20;27:6160-5, 2009), our study shown a modest increased in CTCs after liver metastases resection of advanced CRC. Role of radical metastases surgery in kinetic of CTCs must be analyzed in future studies.
Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia (cll) Prognosis
Authors: Katerina Sarris, Vassiliki Bartzis, Dimitris Maltezas, Efstathios Koulieris, Tatiana Tzenou, Sotirios P. Sachanas, Eftychia Nikolaou, Anna Efthymiou, Katerina Bitsani, Maria Dimou, Theodoros Vassilakopoulos, Marina Siakantaris, Maria K. Angelopoulou, Flora Kontopidou, Panagiotis Tsaftaridis, Nikolitsa Kafasi, Gerassimos A Pangalis, Panayiotis Panayiotidis, Stephen Harding, Marie-Christine Kyrtsonis
Journal: Blood (2012)
Why do patients still go to low-volume hospitals for complex cancer surgery?
Authors: Jason B Liu, Karl Y. Bilimoria, Katherine Mallin, Clifford Y. Ko, David P Winchester
Journal: Journal of Clinical Oncology (2016)

300 Background: While a strong volume-outcome relationship exists for many cancer operations, patients continue to undergo these operations at low-volume centers. Methods: Patients were identified from the National Cancer Data Base (NCDB) from 2010-2014 who underwent resection for bladder, breast, esophagus, stomach, pancreas, lung and rectal malignancies from 1,406 hospitals. Low-volume hospitals were defined as those in the bottom quartile by surgical volume for each operation separately. Regression models were developed to assess patient-level factors associated with undergoing surgery at a low-volume hospital for their malignancy. Results: Of 633,853 patients identified, 49,926 (7.9%) underwent cancer surgery at a low-volume hospital. The low-volume threshold was 1 case/year for bladder, 34 for breast, 1 for esophagus, 1 for stomach, 1 for pancreas, 5 for lung, and 2 for rectal cancers. For all the cancer surgeries examined, patients were more likely to undergo surgery at a low-volume hospital if they lived in a rural area or if they already had to drive a long distance just to reach the low-volume hospital. Patient demographics, socioeconomic factors, insurance type, comorbidities, and stage of disease were not consistently associated with undergoing surgery at a low-volume hospital across all malignancies. Although breast cancer is a common cancer with a less established volume-outcome relationship, the factors associated with undergoing surgery at a low-volume hospital were similar to those of the more complex cancer operations. Conclusions: Patients continue to undergo surgery at low-volume hospitals due to where they live and how far they have to travel. Regionalization policy initiatives will remain challenging in this population. Efforts should therefore continue to emphasize quality improvement locally at each facility caring for patients with cancer.
Integrated research platform (iGXT) for enhancing drug development and personalizing cancer therapy: Pilot study results.
Authors: D. R. Gandara, T. A. Van Dyke, Z. Weaver Ohler, T. Li, P. Lara, P. C. Mack, R. F. Calhoun, R. Gandour-Edwards, K. D. Danenberg, R. de Vere White, N. Goodwin
Journal: Journal of Clinical Oncology (2011)

3053 Background: New approaches to drug development in both the laboratory and clinic will be required to achieve the goal of personalized and molecular-based cancer therapy. Here we describe an integrated research platform (iGXT) engaging unique resources at The Jackson Laboratory (JAX-WEST), the NCI Center for Advanced Preclinical Research (CAPR) and the UC Davis Cancer Center. Non-small cell lung cancer (NSCLC) was selected for pilot studies employing this strategy due to molecular targets of interest, such as epidermal growth factor receptor (EGFR), heterogeneity in NSCLC tumor biology and the complexity of cancer signaling pathways. Methods: In pilot studies, EGFR-directed drugs of interest (example AKT inhibitor MK2206) are studied at NCI CAPR in genetically engineered mice (GEMs) bearing tumors with defined EGFR-related characteristics while NSCLC patients (pts) and JAX Nod Scid Gamma (NSG) mice with patient-derived xenografts (PDXs) from those pts are concurrently treated in a co-clinical trial paradigm, taking advantage of superior properties of the NSG mouse for propagating PDXs. Results in NSG models and pt trials are assessed by genome-wide technologies, integrated with data from CAPR, and extrapolated back to individual pts. Results: Tumor specimens from over 180 cancer pts have been xenotransplanted into NSG mice (~50 from NSCLC). Pilot studies at CAPR in GEMs with EGFR mutant (Tet-op-EGFR L858R +/- T790M) tumors demonstrate efficacy of MK2206 +/- erlotinib, and with the pan-EGFR inhibitor BIBW2992. Complementary in vitro studies at UCD confirm the ability of MK2206 to overcome c-MET-related resistance to erlotinib. An erlotinib-MK2206 clinical trial is ongoing. Demographics of host pts, histopatholgic features and molecular profiles will be presented. Conclusions: This pilot project supports the feasibility of systematically integrating data derived from iGXT models in order to optimize drug development and treatment strategies. Findings from this platform are likely to advance understanding of differences in intra-patient tumor biology and hasten the transition to personalized cancer therapy.
Dosimetric predictors of sexual function decline following LDR brachytherapy for prostate cancer (PCa).
Authors: Omar Y Mian, Scott P. Robertson, Amol Narang, Sameer Aggarwal, Hee Joon Bae, Carol Gergis, Todd R. McNutt, Phuoc T. Tran, Theodore L. DeWeese, Danny Song
Journal: Journal of Clinical Oncology (2016)

113 Background: Conventional dosimetric standards for implant quality do not adequately predict patient reported QoL measures following prostate brachytherapy. We used a dynamic learning knowledgebase (Oncospace) to explore relationships between dose and patient-reported outcomes. Methods: Patient reported quality of life outcomes were prospectively collected for 366 patients with stage cT1-T2 PCa over a 10 year interval. Patients received Pd-103 seed implantation under real-time ultrasound guidance, and completed a QoL instrument (IIEF-5) prior to treatment and at follow-up. Multivariate risk models were used to evaluate dose/toxicity relationships and the Oncospace learning environment generated prediction models using granular dose volume relationships. Results: Median follow-up was 36 months (SD 28.5). In the cohort, 23.7% (n = 87) received combined brachytherapy and EBRT; 14.7% (n = 54) had received prior androgen suppression therapy. Sexual QoL data at minimum of 2 years was available in 141 men. The mean decrement in sexual function per the IIEF-5 instrument was 3.76 points (SD 10.3), with 17.0% of men reporting a decrement of 10 points or greater. There was no significant association with prior androgen suppression (p = 0.20) or combined EBRT use (p = 0.69). DVH curves were queried and dichotomized according to stable sexual function vs significant decline ( &gt; 10) at 2 years post-implant. A logistic regression model was used to generate probability surface maps of volumetric dose effects on outcomes. Logistic regression revealed a correlation between dose to the cavernosal nerves and total SHIM score throughout the high dose region of the DVH curve (p &lt; 0.05). No similar dose/volume correlation with sexual function emerged for structures. Conclusions: Granular dose/volume and toxicity correlation using the Oncospace learning environment exposed a statistically significant relationship between volumetric dose to the cavernosal nerves and sexual function decline in patients undergoing LDR brachytheramarpy. Minimization of dose to the cavernosal nerves may preserve sexual function after permanent prostate seed brachytherapy.