tbuckley/cabot-search huggingface dataset:
The risk of second primary cancers in clear cell and papillary renal cancer.
Authors: Muhammad Saad Hamid, Raji Shameem, Rishi Jain, Kevin M. Sullivan
Journal: Journal of Clinical Oncology (2015)

446 Background: Renal cell carcinoma (RCC) survivors have an increased risk of developing second primary cancers. We sought to determine the role of RCC tumor histology for the risk of developing second primary solid tumors. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to detect RCC cases diagnosed up to 12/31/2011. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cases of second primary malignancy based on incidence data in the general United States population. The two most common RCC histological subtypes were included; clear cell and papillary. The latency exclusion period from the date of diagnosis was 60 months. We investigated for the effect of latency period after initial diagnosis (5-10 years and &gt;10 years) that may increase the risk for a second primary cancer. Results: A total of 2,669 patients with an initial diagnosis of RCC (clear cell: 2,368, papillary: 301) that developed second primary cancers were included in our analysis. There was a significantly increased risk of thyroid cancer (SIR: 2.30, p&lt;0.05), prostate cancer (SIR: 1.12, p&lt;0.05) and “all solid tumors” (SIR: 1.14, p&lt;0.05) in clear cell RCC cases. Regarding latency period, thyroid cancer (SIR: 2.87, p&lt;0.05) risk was increased in the 5-10 years latency period, but not in the &gt;10 years latency period. Overall, in patients diagnosed with papillary RCC, tumors of the prostate (SIR: 1.30, p&lt;0.05), lung (SIR: 1.78, p&lt;0.05) and pancreas (SIR: 2.70, p&lt;0.05) were increased. Exclusively in the 5-10 years latency period, the risk for developing lung cancer (SIR: 1.90, p&lt;0.05) was significant. Conclusions: RCC histology may impact the risk for developing specific second primary solid tumors.
Role of emergent palliative radiation therapy in the care of patients with cancer.
Authors: Lisa Singer, Michael Zhang, Steve E. Braunstein, Shannon E. Fogh
Journal: Journal of Clinical Oncology (2016)

201 Background: Radiation therapy (RT) provides an important role in the palliative care of patients with cancer. For patients with metastatic spinal cord compression not amenable to surgery, the value of timely palliative RT is well established; however, the value of the rapid application of RT for other chief complaints is less clear. The importance of palliative care service (PCS) involvement in patients treated with RT is becoming increasingly recognized and rapidly instituted RT could compromise this involvement. The purpose of this study was to assess the efficacy of emergent RT in alleviating symptoms in patients with cancer and to assess the extent of PCS in the management of patients treated with emergent RT. Methods: Patients treated with emergent RT were retrospectively identified through automated search of our institution’s radiation oncology electronic health record (EHR). Emergent RT was defined as treatment with RT in 48 hours or less from the time of simulation and flagged as emergent in the EHR by the radiotherapy team. Patients without a diagnosis of cancer were excluded from the study. For patients meeting inclusion criteria, data was collected regarding the chief complaint, completion of treatment, length of RT, and the primary outcomes of involvement of PCS and symptom relief. Results: From January to July 2015, 22 patients with cancer were treated with emergent RT. Prior to RT, 21 of 22 patients received other medical and/or procedural interventions. Sixty-four percent of patients were treated with 5 or fewer fractions and all but 2 patients completed RT. Symptoms improved in 73% of patients. PCS were involved in the care of 36% of patients. Conclusions: Emergent palliative RT provided symptom relief in the majority of patients; however, this study identified a lack of PCS involvement in the care of patients treated emergently. Study of long-term patient outcomes is needed. Future work should focus on developing clinical workflows that will better integrate involvement of PCS in the treatment of patients with palliative RT administered both emergently and non-emergently.
Comparison of MPC-6827 activity in xenograft models with different dosing schedules.
Authors: J. T. Jones, V. R. Baichwal, L. Reeves, C. Bradford, D. I. Papac, K. H. Zavitz, A. A. P. Beelen, G. G. Mather, R. O. Carlson
Journal: Journal of Clinical Oncology (2011)

e13080 Background: MPC-6827 is a small molecule microtubule disrupting agent that is being evaluated in phase II studies for the treatment of glioblastoma multiforme. It crosses the blood-brain barrier and achieves brain to plasma concentration ratios of up to 30 in animal models. MPC-6827 is active in multiple xenograft models when dosed on a weekly schedule. Here we explore its activity when dosed on a daily schedule or continuously for 24 hours. Methods: B16 mouse melanoma or OVCAR3 human ovarian cancer cells were implanted subcutaneously into athymic mice (nu/nu) for xenograft studies. MPC-6827 was dosed intravenously (IV) at its maximal tolerated dose of 7.5 mg/kg once or daily at 1 mg/kg for five days for the B16 study. For the OVCAR-3 study, MPC-6827 was dosed at 5 mg/kg once IV or at 2.5-, 5- or 10 mg/kg/day intraperitoneally (IP) with an Alzet mini-pump for one day. Results: In the B16 model, MPC-6827 dosed at 7.5 mg/kg resulted in 72% tumor growth inhibition (TGI) on Day 7 relative to vehicle (p=0.01), whereas 1 mg/kg daily dosing for five days resulted in only 22% TGI (p=0.68). In the OVCAR-3 model, MPC-6827 delivered IP at 2.5 mg/kg over a period of 24 h resulted in no inhibition of xenograft growth relative to vehicle on Day 17. In contrast, the single 5 mg/kg IV dose resulted in 50% regression. The median time to tumor volume >1,500 mm3 was 31 days for the vehicle group, 28.5 days for the 2.5 mg/kg/day IP group and >39 days (p=0.04) for the 5 mg/kg IV group. Plasma concentration of MPC-6827 was 35 ng/mL at 24 h when delivered IP at 2.5 mg/kg/day, whereas Cmax was 1291- and 105 ng/mL with a 5- and 1 mg/kg IV dose, respectively. The AUC for the 5- and 1 mg/kg doses were 657- and 79 hr*ng/mL, respectively. Conclusions: MPC-6827 shows significant activity in animal models when dosed intermittently at 5 mg/kg or higher. Anti-xenograft activity is not observed when the single dose is divided into proportionately smaller daily doses or when the compound is dosed continuously for 24 hours. Thus the optimal dosing regimen for MPC-6827 in xenograft models is intermittent high doses, which result in transiently elevated plasma concentrations of the compound.
Evaluation of olanzapine for breakthrough emesis in patients with cancer not responding to standard antiemetic regimen.
Authors: S. Chanthawong, S. Subongkot, A. Sookprasert
Journal: Journal of Clinical Oncology (2011)

e19596 Background: To evaluate the safety and efficacy of olanzapine for breakthrough emesis in addition to standard antiemetic regimen in cancer patients receiving moderately to highly emetogenic chemotherapy. Methods: A phase II prospective open label clinical trial was conducted in 46 cancer patients diagnosed with solid tumors including breast cancer, colorectal cancer, germ cell tumor, head and neck cancer, malignant melanoma, non small cell lung cancer, osteogenic sarcoma, ovarian cancer, prostate cancer and soft tissue sarcoma who were scheduled to receive at least 1 cycle of moderately to highly emetogenic chemotherapy every 2 to 4 weeks. Each patient received standard antiemetic consisting of generic form of ondansetron plus corticosteroids and metoclopramide according to an oncology clinical practice guideline. Olanzapine was administered as a 5 mg orally every 12 hours for two doses in patients experiencing breakthrough emesis at least one episode despite standard prevention. The efficacy and tolerability were evaluated every 6 hours for 24 hours. Results: From evaluable 46 patients enrolled during September 2009 to July 2010, we reported a major respond of 78.2% which can be categorized as complete response (no emesis) of 60.8% and partial response (one emesis) of 17.4%. Adverse events in olanzapine arm were mild and tolerable including dizziness, fatigue and dyspepsia. Conclusions: Olanzapine is highly effective and considered to be safe for the treatment of breakthrough emesis in cancer patients undergoing moderately to highly emetogenic chemotherapy.
Geriatric factors to predict toxicity and dose-intensity reduction in FFCD 2001-02 phase III study comparing a first-line chemotherapy of LV5FU2 or FOLFIRI in treatment of metastatic colorectal cancer (mCRC) in elderly patients.
Authors: T. Aparicio, J. Jouve, L. Teillet, D. Gargot, V. Le Brun Ly, J. Cretin, C. Locher, O. Bouche, G. Breysacher, J. Charneau, J. Seitz, M. Gasmi, F. Ricard, F. Subtil, E. Mitry
Journal: Journal of Clinical Oncology (2011)

9111 Background: Elderly patients form a heterogeneous population. The evaluation of geriatric factors could help the selection of eligible patients for an intensified chemotherapy. Methods: Elderly pts (75+) with previously untreated mCRC were randomly assigned to receive a 5FU-based CT, either alone (FU arms: LV5FU2 or simplified LV5FU2) or in combination with irinotecan (IRI arms: LV5FU2-CPT11 or FOLFIRI) from 2003 to 2010. Sites participating to the geriatric sub-study, completed Karnofsky, Charlson index and a visual analogue scale (VAS) of quality of life (QoL) at inclusion. Cognitive function, autonomy and depression were assessed with MMSE, IADL and GDS score respectively. Clinical and biologic tumour factors were also analysed to determine predictive factors of grade 3-4 toxicity and reduction of chemotherapy dose-intensity >33% during the first 4 months after randomization. Results: Geriatric score were fullfilled in 123 (48%) pts randomized in FFCD 2001-02 study. Median age: 80 years [75 to 91], 66 men (54%), FU 50.4%, IRI 49.6%. Karnofski index was 60-70, 80-90 and 100 in 32, 32 and 36% of pts respectively and Charlson was <1 or >1 in 75 and 24% of them. Median QoL VAS: 7.9 and median MMSE: 28/30. GDS and IADL were impaired in 45% and 37% of the pts. Seventy-one (58%) pts had a grade 3-4 toxicity and 81 (66%) pts had a dose-intensity reduction >33% during the first 4 months after randomization. In multivariate analysis significant predictive factors of a toxicity grade 3-4 were: no previous adjuvant chemotherapy OR=8.33, IRI arms OR= 3.67, MMSE ≤27/30 OR=5.00 and impaired IADL OR=4.35. Significant predictive factors of a dose-intensity reduction >33% were: phosphatase alkaline >2N OR=8.34, IRI arms OR=6.93 and a linear decrease of MMSE OR=24.3 (each 10%). Conclusions: For the first time in a randomized prospective phase III study in mCCR, geriatric factors (MMSE and IADL) are predictive of severe toxicities or dose-intensity reduction. These results suggest that cognitive function and autonomy impairment should be considered for the chemotherapy regimen choice.
Validation of a trimodalitiy treatment and selective organ preservation for bladder cancer: Influence of clinical different parameters on the 15-year long-term outcome.
Authors: F. Krause, O. Ott, L. Haeberle, B. Wullich
Journal: Journal of Clinical Oncology (2010)

4575 Background: To evaluate our 15-year long-term experience with patients treated with transurtehral resection of the bladder (TURBT) and radiochemotherapy (RCT)/radiation (RT) for bladder cancer and to describe the association of different parameters with clinical outcomes. Methods: All 473 patients undergoing TURBT and RCT/RT for transitional-cell carcinoma (TCC) of the bladder were evaluated, the median follow- up was 5.9 years. RT was initiated 4-6 weeks after TURBT. The TURBT aimed a maximal, complete resection of the tumor mass. Chemotherapy was given simultaneously for 5 consecutive days during the first and fifth week of RT. Investigated were all available parameters: infiltration depth, grading, status of lymph node and distant metastasis, lymphatic vessel invasion, tumor focality, response rate, status of resection/residual tumor and RCT versus RT-only therapy. The estimated survival functions were plotted as Kaplan-Meier curves. Log-rank tests were performed to test whether two or more functions are identical. Results: Long-term results of TURBT with RCT/RT is statistically significant influenced by the following parameters: pT-stage (pT1 vs. pT2/3 vs. pT4), lymph invasion (pL0 vs. pL1), residual tumor status after TURBT (R0 vs. R1 vs. R2), local (cN0 vs. cN+) and distal metastasis (cM0 vs. cM1), kind of therapy (RCT vs. RT), and the response rate (complete vs. non-response) in the control-TURBT. No influence on outcome was seen for associated Cis, grading (GII vs. GIII) and tumor focality in the bladder (uni- vs. multifocal). In a second subgroup analysis of patients with TURBT and complete RCT (n = 331 patients) these statistically significant statements could be confirmed. Conclusions: These data from a large group of patients support a non-aggressive management of invasive TCC. To achieve the same long-term success as radical cystectomy, patients must provide the following parameters: max. stage of pT1, no lymphatic vessel invasion, a microscopically complete TURBT, no evidence of local and distant metastasis, and a complete RCT with complete response in the control-TURBT. No significant financial relationships to disclose.
Long Term Efficacy and Safety Results and Analysis of Dose Correlations from the Phase I/II Peginvera Study of Ropeginterferon Alfa-2b, a Novel IFNa-2b, in Polycythemia Vera Patient
Authors: Heinz Gisslinger, Veronika Buxhofer-Ausch, Josef Thaler, Ernst Schlögl, Gunther Gastl, Dominik Wolf, Martin Schalling, Bettina Gisslinger, Sarita Ban, Alexander Egle, Thomas Melchardt, Sonja Burgstaller, Ella Willenbacher, Maria Theresa Krauth, Nicole C.C. Them, Robert Kralovics, Michael Zörer, Oliver Ammann-Mwathi, Pavla Kadlecova, Oleh Zagrijtschuk, Christoph Klade, Richard Greil
Journal: Blood (2015)
Why do cancer patients rarely participate in clinical trials?
Authors: M. Fouad, J. Lee, C. I. Kiefe, P. Catalano, T. Vogt
Journal: Journal of Clinical Oncology (2008)

6561 Background: Although clinical trials are crucial for improving cancer treatment, very few patients enroll. The Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium was designed to understand treatment choices and outcomes among lung and colorectal cancer patients, in an observational population-based study of newly diagnosed cancer patients across 5 geographic areas, 5 health- care delivery systems, and 10 VA hospitals. Here we examine patient and provider factors related to enrollment in clinical trials. Methods: Data originated from three sources: patient surveys, surveys of these patients' physicians, and medical records. Enrollment in a clinical trial was based on all three sources. Results: Of 9,762 eligible patients, 538 (5.5%) enrolled in a clinical trial. In multivariable analysis, women, older patients, minority patients, and those with early-stage disease were less likely to enroll in clinical trials. Of 4,488 physicians responding to the survey, 21% were surgeons, 14% medical oncologists, 6% radiation oncologists, and 58% non-cancer specialists. Overall, 3.3 % of physicians expected their income to increase from clinical trial enrollment: 11% oncologists vs. 2–4% others. Those expecting an income increase reported a mean (SE) of 15.6 (1.4) patients enrolled over the previous year, vs. 7.3 (0.4) for all others, with the greatest impact of this expectation on trials sponsored by pharmaceutical firms (Table). When combining all data sources in multivariable analyses, the strongest predictor of enrollment was one of the patient's physicians reporting to have enrolled patients in a pharmaceutical trial over the previous year: adjusted odds ratio (95% CI) of 2.27 (1.83–2.82). Conclusions: Physicians play a key role in clinical trial enrollment, and financial incentives to physicians may have significant impact on recruitment. Physicians who have enrolled patients during the past year, by sponsor and income change expectation Expected Income Change Clinical Trial Sponsor NCI Non- NCI Pharmaceutical firm Any clinical trial Expected income increase 52% 36% 64% 82% Did not expect income increase 40% 14% 27% 53% p-value for comparison 0.026 <0.001 <0.001 <0.001 No significant financial relationships to disclose.
Improved intraperitoneal chemotherapeutic toxicity profile for ovarian cancer: A modification of the taxane-platinum protocol in GOG-172
Authors: L. G. Seamon, M. J. Carlson, D. L. Richardson, D. E. Cohn, J. M. Fowler, L. J. Copeland, D. M. O'Malley
Journal: Journal of Clinical Oncology (2008)

5583 Background: GOG 172 demonstrated a significant survival advantage for intraperitoneal (IP) versus intravenous (IV) chemotherapy in optimally debulked ovarian cancer patients; however this treatment was also more toxic. Our objective is to describe the toxicity profile of a modified IP regimen. Methods: A chart review of all ovarian cancer patients who received IP chemotherapy from 12/2005 to 1/2008 was performed. All optimally debulked patients after primary surgery for ovarian cancer who underwent day 1 IV docetaxel 60–70 mg/m2, IP cisplatin 80–85 mg/m2 and day 8 IP paclitaxel 60–70 mg/m2 every 21 days were included. All patients received G-CSF support. Toxicities were recorded using CTCAEv3.0 criteria. Results: 37 patients met inclusion criteria, including 6 patients who previously received 3–4 cycles of neoadjuvant chemotherapy. 34 patients have completed chemotherapy and 3 patients are still undergoing treatment. 59% of patients (20/34) completed all planned cycles of IP chemotherapy and 85% (29/34) completed 50% or more of the planned cycles. 5 patients did not complete ≥ 50% of cycles. 3 of these 5 resulted from port failure, 1 patient developed an abdominal wall abscess requiring port removal, and a final patient had a vaginal vault evisceration during the first cycle of chemotherapy. Toxicity was evaluable for 37 patients and survival in 34 patients. The median number of completed cycles was 5 (range 0.5–7). Overall, 150.5 cycles were delivered with only 6 cycle delays. 9 patients required minor (10–15 %) dose reductions due to side effects. Grade 3 and 4 hematologic toxicities occurred in 12% of patients (4/34). 6 patients experienced grade 3 or 4 non-hematologic events. The overall response rate was 100% (CR=92%, PR=8%) with a median follow up time of 9 months (range 2–27 months). 7 patients have recurred (4 of these patients were platinum resistant). Conclusions: This modified IP regimen is well tolerated. In contrast to GOG 172, major toxicities were markedly reduced and most patients were able to complete > 50% of the planned cycles. These findings suggest that modification of the drugs, dose and schedule of IP chemotherapy should be further studied in future prospective chemotherapy trials in ovarian cancer. No significant financial relationships to disclose.
Retrospective analysis of patients with advanced pancreatic cancer under palliative treatment and additive intratumoral application of viscum album L.
Authors: F. Schad, D. Buchwald, A. Merkle, S. Popp, M. Kroez, H. Matthes
Journal: Journal of Clinical Oncology (2011)

e14538 Background: Patients with advanced pancreatic cancer face poor prognosis. At diagnose > 80% are in stage III with unresectable status or in metastatic stage IV. Viscum album L. extracts (VAe) have shown direct cytotoxicyty, induction of apoptosis and immunmodulating effects in tumor cell lines, animals and humans. Anticancer activity and tumor shrinkange was described after intratumoral injection in a human pancreatic cancer xenograft mouse model. Single case reports and case series show local cancer control after intratumoral application of VAe. Methods: 39 patients (pat.; 22male/17female), medium 61y were treated at an in and out patient clinic setting based on single case treatment decisions between 2004 and 2010. Additional to chemotherapy (ctx) VAe was intratumorally applicated in propofol sedation under standard monitoring transabdominal ultrasound guided (Aloka 10, 0.95-1.2mm Chibaneedles 150 or 220 mm) or transgastric by endosonography (Olympus GF UCT 140 linear, Wilson Cook needles). Results: Starting local treatment 8 patients were in stage III, 31 patients in stage IV. 31 pat. had 1st-line ctx gemcitabine, 10 pat. had combinated 2nd-line ctx. In total 39 patients had 211 intratumoral VAe applications (apl.). 25 pat. had 1- 6 applications, 10 pat. 7-11, 3 pat up to 20 apl., Median 5,4 apl./pat. were administered. 24 apl. (11%) where followed by fever from 38.2-40°, after 22 apl. (10%) elevated temperature up to 38,2° was documented. Other side effects where pain in 10 apl. (4,5%), vomiting in 10 apl. (4,5%), 4 x general skin reaction (1,8%). No SAE was observed. Over all survival (OS) in stage III pat. was 12,2, in stage IV 11,2 months. 15 pat. lived at the end of observation. Conclusions: This retrospective analysis of 39 pat. with additive intratumural application of VAe to guideline based ctx shows an acceptable side effect profile and a prolongation in OS in patients with stage III / IV pancreatic cancer. The therapy is save.
Safety and efficacy of combination therapy with low-dose gemcitabine, paclitaxel, and sorafenib in patients with cisplatin-resistant urothelial cancer.
Authors: Yasuyoshi Miyata, Kojiro Ohba, Tomohiro Matsuo, Hideki Sakai
Journal: Journal of Clinical Oncology (2016)

418 Background: Various chemotherapeutic regimens have been examined. However, there is no effective regimen, and some studies have been stopped because of severe adverse events. Therefore, maintenance of quality of life is also important. This study examine the anti-cancer effects, changes in the quality of life (QoL), and safety of combined therapy of low dose gemcitabine, paclitaxel, and sorafenib in these patients. Methods: Twenty patients were treated with gemcitabine (700 mg/m 2 on day 1), paclitaxel (70 mg/m 2 on day 1), and sorafenib (400 mg/day on days 8–22). QoL and pain relief were evaluated using the short-form survey (SF)-36 and the visual analogue scale (VAS). Data on QoL and pain were collected on the day before the first cycle was started and 8 weeks after starting the therapy. A total of 124 cycles were administered and the median (IQR) number of treatment cycles per patient was 5 (3–8) cycles. Results: Among 20 patients, 12 and 8 patients were received as 2nd- and 3rd-line therapy, respectively. In 2nd-line therapy, median / interquartile range of VAS scores after therapy (2 / 2–3) significantly decreased (p = 0.012) compared to their pretreatment levels (3 / 2–5). Likewise, a significant decrease was also found in 3rd-line therapy (5/ 4–6 to 3/ 2–3, p = 0.028). Similar findings were confirmed by the bodily pain score from the SF-36 survey. A decrease in analgesic consumption was seen in three patients (17.6%), and 2 patients (11.8%) was improved the pain without increasing the dose. Complete responses, partial responses, and stable disease were found in 0 (0.0%), 1 (5.0%), and 13 patients (65%), respectively. The period of overall survival after starting of this therapy was 7 (5–11) months. Three patients (15.0%) stopped therapy because of grade 3 fatigue and hand-foot reactions. Conclusions: Combined therapy of low dose gemcitabine, paclitaxel, and sorafenib was well tolerated. QoL was maintained and improvements in their pain levels were found after treatment. We suggest that this treatment regimen is worthy of consideration as 2nd- and 3rd-line therapy for patients with CDDP-resistant UC. Clinical trial information: 000010957.