tbuckley/cabot-search huggingface dataset:
Clinical characteristics and outcomes of patients with primary mediastinal germ cell tumors.
Authors: Siwat Sakdejayont, Chirawadee Sathitruangsak, Patrapim Sunpaweravong, Arunee Dechaphunkul
Journal: Journal of Clinical Oncology (2014)

389 Background: Mediastinal germ cell tumors (MGCTs) account for 20% of all mediastinal tumors. Cisplatin-based chemotherapy followed by surgical resection of residual tumor remains the standard of care. To prevent pulmonary complications secondary to extensive thoracic surgery, non-bleomycin containing regimen is generally preferred. This study aims to review clinical characteristics and outcomes of these patients. Methods: A retrospective chart review was undertaken in patients with MGCTs treated in our institution between 1993 and 2013. Results: A total of 40 patients were enrolled with a median age of 24. Only one patient is female. Stratified by histology; eight patients (20%) had pure seminoma, 25 patients (62.5%) had pure non-seminoma, four patients (10%) had mixed seminoma and non-seminoma, and three patients (7.5%) had malignant transformation (two adenocarcinoma, one sarcoma). Median tumor size was 13 centimeters. Ninety-two percent of patients received chemotherapy as a first treatment modality, whereas 8% underwent upfront surgery. All patients received cisplatin-based chemotherapy: Eighty seven percent bleomycin, etoposide and cisplatin; 13% etoposide and cisplatin. Seventy-two percent of patients completed four planned cycles of chemotherapy. Thirty-one patients were able to assess radiological response: 3.2% complete response, 58.1% partial response, 29.0% stable disease, and 9.7% progressive disease. Forty-four percent of patients achieved completely serological response with chemotherapy. Seventeen patients underwent surgical resection of residual tumor. Among these, viable tumor was seen in 35% (6 out of 17 patients). No patients complicated with clinically significant pulmonary complications after thoracic surgery. The five year overall survival (OS) of patients with seminoma was 72.9% as compared with 19.9% in those with non-seminoma (p=0.012). For those who received chemotherapy followed by surgical resection with no viable tumor or only mature teratoma detected (N=11), the five year OS was 64.9%. Conclusions: Our study confirmed the importance of multi-modality approaches with primary chemotherapy followed by surgical resection of residual tumor. Bleomycin-containing regimen can be safely used in this setting.
Postdocetaxel treatment for castrate-resistant prostate cancer: The sequential use of abiraterone and cabazitaxe.
Authors: David Gareth Fackrell, Nicholas David James, Daniel Ford
Journal: Journal of Clinical Oncology (2013)

234 Background: Large phase III trials have shown both abiraterone (Abi) and cabazitaxel (Cbz) to have a survival benefit in patients with metastatic castrate resistant prostate cancer (mCRPC). They are now used routinely throughout the UK in this setting. The mechanisms of resistance of these drugs remain unclear and therefore, their sequential use is less recognised. We present data from patients who have been exposed to both therapies. Methods: In this retrospective study, we searched our own pharmacy databases to identify all patients that had been exposed to both Abi and Cbz. All patients were treated between April 2009 and October 2012. A total of 21 patients were reviewed and clinical data was collected. SPSS software was used to create Kaplan Meier curves. Results: 17 of the 21 patients received Abi before Caz. Median progression free survival for patients on the sequential regimes was 16.9 months (95% Confidence interval: 10.5-23.3). Reviewing the drugs individually found progression free survival was 5.1 months (4.4-6.0 months) with Abi and 7.1 months (5.1-9.1) with Cbz. Conclusions: In a select group of patients who are fit enough to receive both drugs, superior progression free survival is seen than can be expected on one drug alone. The data compares favourably to that seen in the TROPIC study where time to progression on Cbz was 2.8 months. Furthermore, lack of response to one drug did not preclude worthwhile response to the other agent. These findings are consistent with the drugs having separate mechanisms. At this stage the series is not mature enough to draw conclusions on survival benefit. An updated series, involving larger patient numbers, will be presented at the meeting.
Increase in blood pressure with sorafenib exposure: Renal cell carcinoma (RCC) versus other solid tumors.
Authors: Amishi Shah, Shweta Motiwala, Marcia S. Brose, Peter J. O'Dwyer, Keith Flaherty, Stephen Michael Keefe
Journal: Journal of Clinical Oncology (2013)

e15564 Background: Tyrosine kinase inhibitors (TKIs) such as sorafenib are widely used in the treatment of solid tumor malignancies. Incident hypertension with angiogenesis inhibitors has been well-documented in the RCC where incident hypertension on treatment is associated with improved clinical outcome. Little has been reported about increases in (BP) with TKIs in other solid tumor malignancies. Methods: We performed a retrospective cohort study examining changes in BP with sorafenib among the 101 patients treated at the University of Pennsylvania on a randomized discontinuation trial examining sorafenib in patients with advanced solid tumor malignancies. Solid tumor diagnoses were established on the basis of tumor histology. Treatment of patients on study with sorafenib was initiated at 400 mg BID. Patients were treated for at least 12 weeks and were evaluated at least every three weeks in the clinic. BP was recorded at each visit. Sorafenib exposure was recorded by patients in a pill diary. The primary endpoint for this study was a maximal change in BP defined as the difference between baseline BP and highest subsequent recorded systolic and diastolic BPs on treatment. Results: 72% of RCC patients developed an increase in systolic BP (SBP) of at least 20 mmHg as compared to 32% of non-RCC patients. The mean increase in SBP on study for RCC patients was 30 mmHg versus 19 mmHg in non-mRCC patients. RCC patients in the top quartile of increased SBP showed a mean increase of 54 mmHg as compared to 35 mmHg for non-mRCC patients. A chi-squared test of proportions and t-tests were used to compare rates and means, respectively. Each of the aforementioned differences were found to be statistically significant with p-values &lt;0.003. These relationships also held true for diastolic BP. There was no difference in SBP between groups in terms of age or sorafenib exposure. Differences in BP were not related to differences in glomerular filtration rate. Conclusions: In these sorafenib-treated patients, the proportion of patients with increased BP and the mean amplitude of change in BP both were significantly greater in the RCC population than in the non-RCC group.
Total estrogen blockade (TEB) plus adjuvant chemotherapy in high-risk estrogen receptor-positive (ER+) premenopausal breast cancer: Long term results of an ovarian protection study
Authors: F. Recchia, G. Candeloro, S. Necozione, M. Sureda, M. Bratta, R. Bisegna, S. Rea
Journal: Journal of Clinical Oncology (2008)

11541 Background: Randomized trials have established that ovarian suppression with luteinizing hormone-releasing hormone (LHRH) agonists is an effective adjuvant treatment in premenopausal patients with ER+ breast cancer, not inferior to chemotherapy (JCO 2007; 25: 2509). Whether the addition of chemotherapy to LHRH agonists could add some advantage is unknown. We hypothesized that, due to tumor heterogeneity, chemotherapy, added to LHRH, could improve disease-free survival (DFS) and overall survival (OS), by killing cell clones resistant to hormonal therapy. Aim of this study was to evaluate the DFS and OS of 100 consecutive premenopausal patients with high risk, ER+, breast cancer, included in an ovarian protection study, treated with TEB, and adjuvant chemotherapy. Methods: Following surgical treatment, patients received 2 years of LHRH analogue, 6 months of adjuvant chemotherapy, tailored to the individual biologic features of each patient and radiation therapy, if indicated. Chemotherapy included: 5-fluorouracil, methotrexate, anthracyclines, cyclophosphamide, taxanes, carboplatin, in various combinations. After chemotherapy, an aromatase inhibitor was given, simultaneously with the LHRH analogue and continued to patients with amenorrhea. Tamoxifen was given to patients that resumed normal menses. Results: Characteristics: Median age 43 years (range 27–50), 64 stage II disease, and 36 stage III. Serum estradiol was suppressed to values < 40 pg/ml in all patients. Eighty patients were irradiated. After a median follow-up of 7.4 years (minimum 30 months), projected DFS rates at 5, 10 and 15 years were 91%, 87% and 79%, while 5, 10 and 15 years OS rates were 94.2, 90% and 90%, respectively. DFS and OS were not statistically different in patients older or younger than 35 years of age. Normal menses were resumed by all patients below 40 years and by 56% of patients above 40 years of age. Five pregnancies were recorded: 4 at term and 1 voluntary abortion. Conclusions: Due to tumor heterogeneity, chemotherapy, added to an LHRH analogue seems to improve the expected DFS and OS in high-risk premenopausal patients with ER + tumors and compares favorably with DFS and OS from other adjuvant regimens. No significant financial relationships to disclose.
Safety and clinical outcome of a cohort of patients (pts) with castration resistant prostate cancer (CRPC) treated with abiraterone acetate (AA) in a named patient program (NPP): Updated results of a retrospective study from an Italian cooperative group.
Authors: Orazio Caffo, Lucia Fratino, Giovanni Lo Re, Umberto Basso, Alessandro D'Angelo, Maddalena Donini, Daniele Santini, Giuseppe Procopio, Francesco Massari, Donatello Gasparro, Francesco Verderame, Cosimo Sacco, Caterina Messina, Roberto Iacovelli, Fable Zustovich, Giovanni Vicario, Anna Paola Fraccon, Vincenza Conteduca, Francesca Maines, Ugo De Giorgi
Journal: Journal of Clinical Oncology (2014)

253 Background: Abiraterone acetate (AA) provided a survival advantage compared to placebo in patients (pts) with castration resistant prostate cancer (CRPC) who had received docetaxel (de Bono JS et al, NEJM 2011). The present retrospective study is aimed to assess safety and clinical outcome in an unselected CRPC population which received AA in a named patient program (NPP). Methods: We retrospectively reviewed the clinical records of all pts treated with AA for CRPC by NPP in our institutions. All pts have been previously treated with a docetaxel-based first-line chemotherapy and received the standard AA dose of 1,000 mg daily plus prednisone 10 mg daily. For each pt we recorded the pre- and post-AA clinical history, the AA treatment details toxicities and clinical outcomes. Results: To date we have collected a consecutive series of 245 pts from 18 Italian hospitals. The median age was 73 (range 45 to 91). The median baseline prostate-specific antigen (PSA) level was 100 ng/ml (range 0.33-&gt;100.000); 79% of the pts had bone metastases, while nodal, lung and liver metastases were observed in 52%, 9%, and 7% of the pts, respectively. The median duration of AA treatment was 5 months (range, 1 to 26). Grade 3 to 4 toxicities were anemia (11 pts), fatigue (nine pts), bone pain (four pts), constipation (two pts), thrombocytopenia (two pts), nausea (one pt), diarrhea (one pt), dyspnea (one pt), edema (one pt), hypertension (one pt), hyperbilirubinemia (one pt), and hypokaliemia (one pt). A PSA reduction of more than 50% was observed in 50.9% of the pts. The median progression-free survival (PFS) and overall survival (OS) were 6 months and 15 months, respectively; the 1 year PFS and OS rates were 24.3% and 56.9%, respectively. Conclusions: Our results have confirmed the safety and efficacy of AA in an unselected population of pts with pre-treated CRPC outside clinical trials and provided further support concerning the good safety profile of the drug.
Increased level of serum iron and gastrointestinal toxicity in patients with solid tumor treated with cytotoxic chemotherapy.
Authors: T. Miya, M. Inomata, Y. Kokubo, K. Sakai, Y. Kusunoki
Journal: Journal of Clinical Oncology (2011)

e13049 Background: The mechanism of gastrointestinal toxicity of chemotherapy including nausea and vomiting especially in late phase remains unclear. Nausea and vomiting are also known as major side effects of iron supplementation in pregnancy or anemia patients. The relationship between serum iron level and toxicity of chemotherapy was investigated. Methods: A total of 17 patients with solid tumor treated with cytotoxic chemotherapy were examined. The blood samples were taken before and on day 2 or 3 of chemotherapy. The changes of serum iron, unsaturated iron capacity (UIBC) and ferritin were measured to analyze the relationship with adverse effect. Results: The number of patients received each chemotherapy were 5 for carboplatin /gemcitabine, 2 for calboplatin/etoposide, calboplatin/paclitaxel, and irinotecan, and 1 for cisplatin/etoposide, calboplatin/pemetrexed, amurubicin, docetaxel, gemcitabine and pemetrexed. Mean values of iron, UIBC and ferritin before and after chemotherapy were 60.5±18.0 vs. 220.5±17.0μg, 202.5±42.8 vs. 23.0±45.7μg, and 211.4±103.8 vs. 263.5±164.2 ng/ml, respectively. Statistically there were no significant correlation between iron level and adverse effects, however there were tendency that nausea and vomiting of grade 3 or 4 were observed more in patients with higher iron level. Conclusions: Regardless of various chemotherapy regimens, the iron levels on day 2 or 3 of chemotherapy were markedly increased in all patients. Correspondingly, UIBC were extremely decreased and reached to 0μg in 4 patients sufffering severe nausea and vomiting. These results imply that increased radial iron in serum is one of causes of gastrointestinal toxicity, which may be a target of minimizing complications of cancer chemotherapy.
Treatment-related deterioration of renal function as a biomarker to predict antitumor efficacy of sunitinib in patients with metastatic renal cell carcinoma.
Authors: Hironori Fukuda, Tsunenori Kondo, Kenji Omae, Toshio Takagi, Kazunari Tanabe
Journal: Journal of Clinical Oncology (2015)

502 Background: Some on-target adverse events such as hypertension or thrombocytopenia have been reported as biomarkers predicting the efficacy of sunitinib as first-line therapy for patients with metastatic renal cell carcinoma (mRCC). Decrease of renal function is a major adverse event of sunitinib. However, it remains unclear whether the degree of deterioration of renal function can predict the anti-tumor efficacy of sunitinib. We investigated the relationship between treatment-related deterioration of renal function and anti-tumor efficacy in mRCC patients treated with sunitinib. Methods: We retrospectively reviewed the medical records of mRCC patients who were treated with sunitinib for more than 3 months. Patients receiving hemodialysis before receiving sunitinib as well as those who did not undergo nephrectomy were excluded from our analysis. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) calculated using the MDRD equation modified for Japanese patients. The degree of deterioration in eGFR was compared with progression-free survival (PFS). Results: Sixty-two patients were enrolled, the median age was 65 years, and 44 patients (71%) were male. The median baseline eGFR was 49.1 ml/min/1.73m 2 , and median decrease of eGFR was 9.9 ml/min/1.73m 2 . Forty-seven patients (76%) had a decreased eGFR of more than 10% compared to baseline values. The patients showing this decrease had significantly longer PFS than those who did not (PFS: 15.5 months vs. 6.1 months, respectively; p=0.001). On multivariate analysis, a decrease in eGFR of more than 10% was a significant independent factor for predicting longer PFS (hazard ratio, 0.37; 95% confidence interval, 0.17-0.83; p=0.017) as well as MSKCC risk groups and cycles of sunitinib. Conclusions: Treatment-related deterioration of renal function is a biomarker to predict better treatment efficacy for use of sunitinib during first-line therapy for patients with mRCC.
Clinical outcomes of resectable small bowel adenocarcinoma treated by surgery alone: Case series in a Japanese single institution.
Authors: Shoko Noda, Yoshitaka Honma, Hiroshi Moro, Shoko Nakamura, Yusuke Sasaki, Naoki Takahashi, Satoru Iwasa, Natsuko Okita, Atsuo Takashima, Ken Kato, Tetsuya Hamaguchi, Narikazu Boku, Minoru Esaki, Kazuaki Shimada, Shinji Morita, Takeo Fukagawa, Hitoshi Katai
Journal: Journal of Clinical Oncology (2016)

372 Background: Small bowel adenocarcinoma (SBA) is known as a poor prognostic cancer even in surgically resected cases. Its five-year survival rates were reported as 65%, 48%, and 35% in stage I, II, and III SBA, respectively. However, clinical outcomes of curatively resected SBA, especially without peri-operative adjuvant chemotherapy, are still unknown in Japanese population. Methods: We retrospectively reviewed medical records of patients who were diagnosed as Stage I, II, and III SBA after curative surgery between July 1994 and June 2014 at National Cancer Center Hospital. Overall survival (OS) and relapse-free survival (RFS) were calculated by Kaplan-Meier method. Cox proportional-hazards analysis was performed to identify the prognostic factors. Results: From a total of 76 patients with SBA received surgical resection, 56 were selected in this study who underwent curative resection with histological confirmation and did not receive adjuvant chemotherapy. The median age was 64 years (range: 20-85). Thirty-five patients (61%) were male. Forty-five patients (80%) had tumors in duodenum, 6 (11%) in jejunum and 5 (9%) in ileum. Pathological T stage were pT1a/T1b/T2/T3/T4 in 9/2/4/14/27 patients, and pathological N stage (pN) were pN0/N1/N2 in 29/16/11. The 1/3/5-year OS in all patients were 92.5/77.5/71.6%, and 1/3/5-year RFS were 76.5/68.9/61.6%. The 5-year RFS of pN0 (stage I/IIA/IIB) / N1 (stage IIIA) /N2 (stage IIIB) were 81.2/51.6/20.8%, and 5-year OS were 88.2/71.6/26.7%, respectively. Univariate analysis demonstrated that pN, presence of lymphatic and venous invasion were associated with poor OS. In multivariate analysis, pN was a significant predictor of poor OS (HR: 5.39 [N0 vs N1], 21.74 [N0 vs N2], 4.03 [N1 vs N2], p = 0.042). These findings were also seen in RFS. Conclusions: This study showed survival outcome of curatively resected SBA was better compared with previous reports, and pN was a significant prognostic factor of RFS and OS.
Surgical treatment of gastric cancer: Oncologic outcome of neoadjuvant treatment in the German multicenter observational study II.
Authors: Patrick Stuebs, Benjamin Garlipp, Frank Meyer, Ingo Gastinger, Hans Lippert, Joerg Fahlke, Karsten Ridwelski
Journal: Journal of Clinical Oncology (2014)

139 Background: Neoadjuvant chemotherapy is broadly established in European centers when treating locally advanced gastric cancer. However, there still remain questions as to the benefit of this extended form of treatment in regards to tumor location and stage. Methods: Data obtained in the ongoing prospective, multicenter observational study (German Gastric Cancer Study II) on quality assurance in surgical therapy of gastric cancer containing a total of 2897 patients treated from 01/01/2007 through 31/12/2009 in 145 surgical departments to evaluate. Results: Overall, 506 patients (18.4%) received neoadjuvant treatment in regards to all tumor stages. Of the 530 patients with adenocarcinoma of the gastroesophageal junction (GEJ) 34.5% (n=183) received chemotherapy. In detail, 30.1% (n=873) of the patients were found to be in stage I. In regards to the mean time of survival for advanced stages (III/IV 6th editiion) a survival benefit for patients receiving neoadjuvant treatment (n=356) of 12.0 months was demonstrated versus 10.0 months (p=0.048) for patients not being treated neoadjuvantly. Improved survival through neoadjuvant treatment could not be demonstrated in GEJ tumors, both, comparing different types of GEJ and matching cancer of the GEJ and distal gastric cancer. Overall survival in GEJ tumors is significantly lower (25 months) compared to the overall survival in distal gastric cancers (38 months). In addition, 5-year survival rate of GEJ tumor patients (33.1 %) was distinctly lower than for patients with distal gastric cancer (41.4 %). Conclusions: The results reflect the difficulties of applying currently available study results to daily clinical practice. In order to achieve improved treatment results, requirements in diagnostics, oncological and surgical settings are paramount. Future data of this observational study can provide additional insight for this process.
Wait time reduction for patients awaiting chemotherapy infusion using a formal process improvement approach and sequential.
Authors: Andrew David Norden, Lori A. Buswell, Meg Amorati, Lois Arthur, Antoinette Bernard, Michael Constantine, Carole Dalby, Wendy Farrar, Frances Fuller, Dawn Kerivan, Kristin Lacourse, Brendan D. McNulty, Adonica Racicot, Melissa Spinks, Joseph O. Jacobson, Patricia Reid Ponte, Lawrence N. Shulman
Journal: Journal of Clinical Oncology (2012)

92 Background: At a community hospital satellite of an academic cancer center, baseline data indicated that 49% of patients waited longer than 30 minutes from arrival in the treatment chair until treatment was started, resulting in dissatisfaction and decreased chair turnover. Methods: A team was assembled, including physicians, nurses, pharmacists, and administrative staff. The team constructed a detailed process flow map and performed a cause-and-effect analysis. Wait time data were collected using the electronic scheduling system and time sheets. Additionally, nurses used a structured data collection sheet to categorize the reasons for prolonged wait times. A p-type statistical process control chart was constructed to track the proportion of infusion visits per day with wait times longer than 30 minutes. The team brainstormed process improvements and selected ones to implement by employing a priority/pay-off matrix. Results: Baseline data were assessed for 403 visits over a 3 week period. Of 232 visits with wait times longer than 30 minutes, 98 (42%) involved excessive waiting for the physician to see the patient or write orders. One of 4 physicians was responsible for 56 (57%) of these. This physician’s patients were seen exclusively in the infusion room, while the other physicians saw patients in the exam room before sending them to the infusion area. Three PDSA cycles were conducted: (1) All physicians started seeing patients in the exam room before sending them to infusion chairs, (2) Specific treatments were selected that could be routinely administered without the physician seeing the patient, and (3) A reminder system prompted physicians to enter treatment orders within 24 hours of each patient’s visit. After 6 months, 29% of patients waited longer than 30 minutes, down from 49% at baseline. Conclusions: These interventions implemented using PDSA cycles successfully reduced wait times. Measurement and presentation of data were critical in persuading physicians to practice in a more homogeneous fashion.