tbuckley/cabot-search huggingface dataset:
Adjuvant chemotherapy and chemoradiation following surgery for high-risk endometrial cancer.
Authors: K. Narayan, D. Rischin, M. Quinn, J. C. Goh, R. Cheuk, A. Obermair, D. Bernshaw, B. McClure, A. Milner, L. R. Mileshkin
Journal: Journal of Clinical Oncology (2010)

5028 Background: Endometrial cancer with adverse pathology has a significant risk of disease relapse if treated with surgery alone. We performed a prospective phase II trial testing the addition of concurrent chemotherapy during adjuvant radiation followed by adjuvant chemotherapy. Methods: Eligible patients had histologically confirmed endometrial cancer following a minimum of TAH-BSO, plus high-risk features of: node-positive disease, grade 3 FIGO 1988 stage Ic or IIb, or any stage III disease. Stage IV disease, serous or clear cell cancer was excluded. Treatment involved 54Gy of external beam radiotherapy (RT) to the pelvis ±extended field (EFRT) with carboplatin AUC 2 weekly × 6 during RT, followed by 4 cycles of carboplatin AUC 5-6 and paclitaxel 175 mg/m2 q3weeks. The primary endpoint was failure-free survival (FFS), with secondary endpoints of overall survival (OS) and toxicity. Results: 41 patients of median age 57 (range 31-79) were enrolled 06/04 to 08/08. 24 (59%) had stage IIIC disease with 11 (27%) having residual measurable disease on post-operative CT. All completed planned RT, including 11 (27%) treated with EFRT. 32 (78%) received all 6 doses of concurrent chemotherapy, 32 all 4 cycles of adjuvant chemotherapy and 28 (68%) received the planned 10 doses. After a median follow-up of 2.34 years, the estimated 3 year FFS rate was 73% (95%CI: 54-87%) and OS rate was 93% (95%CI: 76- 98%). By the study censor date, 9 patients (22%) had a recurrence with only 2 patients relapsing within the RT field. Treatment was well tolerated with no treatment-related deaths. Grade 3 or 4 nonhaematologic toxicity occurred in 14 with 12% grade 3 diarrhoea and 10% grade 3 arthralgia/myalgia. One pt respectively developed febrile neutropenia and grade 3 sensory neuropathy with 4 (10%) developing platinum-hypersensitivity. Conclusions: Adjuvant chemotherapy after chemoradiation for patients with high-risk endometrial cancer is a promising approach, though distant failure remains the dominant site of failure. This regimen was well tolerated but the high number of carboplatin doses resulted in a 10% hypersensitivity rate. Ongoing randomised trials should be supported to determine the optimum adjuvant therapy in endometrial cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
Formation of an international quality improvement collaborative for palliative care: The Global Palliative Care Quality Alliance (GPCQA).
Authors: Arif Kamal, Jonathan Nicolla, Fred Friedman, Charles S. Stinson, Laura Patel, Keith Mark Swetz, Jacob Strand, Diane G. Portman, Sarah Thirlwell, Hunter Groninger, Howard Tuch, Martha Twaddle, William Kennedy, Andy Kyler, Loretta Matthews, Greg Candell, Karen Baker, Zeba Anwar, Amy Pickar Abernethy, Janet Bull
Journal: Journal of Clinical Oncology (2014)

91 Background: Formal mechanisms to share data on quality remain immature in specialty palliative care. As the field grows, infrastructure that promotes collaboration among academic and community-based practice will be required to foster comparisons and benchmarking of data to inform areas for quality improvement. Further, such relationships will create a palliative care “quality improvement laboratory”, where proposed guidelines and best practices can be developed, implemented, and tested. Methods: We set out to bring together specialty palliative care practices with a shared vision for collaborative quality improvement. We modeled our approach after the Institute for Healthcare Improvement Breakthrough Series alongside our Rapid Learning Quality Improvement paradigm. We use a set of common data collection procedures, across an electronic point-of-care platform called Quality Data Collection Tool (QDACT), alongside a centralized data registry. Further, we meet and discuss challenges and issues, compare best practices, and brainstorm new projects through biweekly conference calls. Results: We have created a multi-institutional collaboration for quality assessment and improvement in specialty palliative care. Termed the Global Palliative Care Quality Alliance, we have brought together 11 academic and community organizations, both general and oncology-specific, across six states to study various areas of quality practice. Short-term, we will conduct rapid-cycling quality improvement projects addressing National Quality Forum domains for quality palliative care, including documentation of spiritual assessment and timely advance care planning. Long-term, we aim to study the link between quality measure adherence and outcomes and further align our initiatives with those of other large consortia, like the Palliative Care Research Cooperative and Palliative Care Quality Network. Conclusions: Collaborative quality improvement is needed in specialty palliative care across a national platform. Developing the infrastructure to perform standardized quality improvement is achievable across multiple palliative care settings.
Young age at first live birth and long duration of breast feeding: Are they universally accepted protective factors against breast cancer? A case control study of the Cancer Research Group in Pakistan.
Authors: M. Masood, S. Ahmed, S. Kanwal, H. Masood, K. Ahmad, A. Mahmood, M. Faheem, N. Akbar, M. Hafeez
Journal: Journal of Clinical Oncology (2010)

1572 Background: This study has been conducted in Pakistan in order to find out the association and relationship of different hormonal and reproductive factors with breast cancer. These factors have been identified either as risk factors or protective factors for breast cancer in other communities but not in Pakistani women. Preliminary results were presented in SABCS 2009 (Cancer Research . Vol 69. Abstr 2071) Here, we present the final results. Methods: Patients were interviewed by the trained medical personals and the findings were recorded in a proforma. Age and area matched unrelated controls were randomly selected and interviewed with same questions. SPSS version 11.5 was used for statistical analysis. Results: From June 2008 to October 2009 thirteen hundred and seventy two cases were compared with an equal number of controls. Median age of cases was 47 years (16-90 years) and controls 48 years (16- 88 years). Three hundred and eighty five of cases (28.06%) and 256 of controls (18.66%) gave first full-term live birth before the age of 20. One hundred and sixteen cases (8.45%)and46 controls (3.35%) gave first full-term live birth after the age of 30. Breast feeding duration was more then 24 months in 947 (84.40%) of all cases and 990 (82.50%) of controls in women with more than one child. Statistical analysis reveals that first live birth below the age of 20 and breast feeding of greater then 24 months duration are not associated as protective factors in this patient population. Odds ratio of 1.86, 95% CI; 1.30-2.66 and 1.14, 95% CI; 0.92-1.42 respectively. Age at first live birth after 30 years of age seems to be positively associated with breast cancer. Odds ratio of 2.84, 95% CI; 2.00-4.03. Conclusions: These results do not support the young age at first full term pregnancy and prolonged duration of breast feeding as protective factors against the breast cancer. No significant financial relationships to disclose.
Extended follow-up of outcome measures and analysis of prognostic factors in multiple myeloma patients treated on a phase I study with bortezomib and pegylated liposomal doxorubicin
Authors: S. E. Biehn, D. T. Moore, P. M. Voorhees, R. A. Garcia, M. J. Lehman, E. C. Dees, R. Z. Orlowski
Journal: Journal of Clinical Oncology (2006)

7617 Background: Preclinical studies of bortezomib (bort) with pegylated liposomal doxorubicin (PLD) showed enhanced anti-tumor efficacy compared with either single agent. This led to a phase I trial in patients (pts) with advanced hematologic malignancies who received bort on days 1, 4, 8 and 11 at 0.9–1.5 mg/m 2 , and PLD on day 4 at 30 mg/m 2 , every three weeks (Blood 105:3058, 2005). Significant activity was seen, with 36% of relapsed/refractory multiple myeloma (MM) pts achieving a complete or near-complete response, while 73% attained at least a partial response. It was therefore of interest to define time to progression (TTP) and overall survival (OS) with this regimen. Methods: Additional follow-up was obtained on all 22 evaluable MM pts. TTP and OS were determined from day 1 of bort/PLD, and the Kaplan-Meier method was used to calculate time-to-event estimators. The log-rank test was used to compare TTP and time to retreatment (TTR) on bort/PLD vs. the prior therapy. Cox regression was used to evaluate covariates for association with TTP and OS. Results: Median TTP with bort/PLD was 9.3 months (mos)(95% confidence interval (CI) 8.3–22.4) versus 3.8 mos (95% CI 2.3–10.0) on the pt’s prior therapy (p=0.04). Similarly, the median TTR after bort/PLD was prolonged (p=0.04) compared with TTR after the prior regimen, with 3 pts having not yet received their next therapy. With a median follow-up of 36 mos, 13 of these patients (59%) remain alive, and the median OS has not yet been reached. Karnofsky performance status was significantly associated with TTP (p=0.02), while the hematocrit (hct; p=0.06) and IgA subtype (p=0.08) had borderline significance. Hct was significantly associated with OS (p=0.03), while the number of prior regimens (p=0.07) and the platelet count (p=0.06) had borderline significance. Conclusions: Bort alone induced a median TTP of 6.6 mos and OS of 16 mos in MM (N Engl J Med 348: 2609, 2003). The current results support the possibility that the bort/PLD regimen may improve upon TTP, and especially OS, compared with bort alone. This hypothesis is being studied in a randomized, international phase 3 trial ( NCT00103506 ) comparing bort and bort/PLD. No significant financial relationships to disclose.
Phase II trial of weekly docetaxel, zoledronic acid and selenium for hormone refractory prostate cancer
Authors: J. G. Kattan, M. Ghosn, G. Chahine, A. Saroufim, F. Nasr, F. S. Farhat
Journal: Journal of Clinical Oncology (2008)

16113 Background: Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results especially when zoledronic acid was included. Moreover, preclinical and clinical trials showed that Selenium significantly reduced malignant prostate cell proliferation and the risk of developing prostate cancer. Methods: We conducted a phase II trial associating weekly Docetaxel, Zoledronic acid and Selenium. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, Docetaxel (25 mg/m2) on days 1, 8 and Selenium orally at 200 microg once daily for 21-day cycle. Results: Thirty one patients were selected but only twenty-seven were enrolled between August 2005 and November 2007. Median age was 67 years (range 53 to 83). A total of 135 cycles were administered with a median of 6 cycles per patient (2–6 cycles). The major toxicities were grades 1 to 2 anemia (37%), alopecia (7.4%) and motor neuropathy (7.4%). Out of the 27 patients assessed for efficacy, only 4 (15%) had a biologic response (>50% PSA decline). A total of 8 patients (30%) experienced clinical benefit with pain reduction. The median survival time was 15 months (95% CI: 11,19) whereas the median progression time was estimated at 6.5 months (95% CI: 5.0,8.1). Conclusions: Combination of weekly Docetaxel, Zoledronic acid and Selenium is a well tolerated regimen but but with limited efficacy. Adding Selenium to chemotherapy does not seem offering any therapeutic advantage. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis
Chemotherapy for patients with advanced gastric cancer with performance status 2
Authors: K. Muro, K. Shitara, T. Ura, D. Takahari, T. Yokota, A. Sawaki, H. Kawai, M. Munakata, Y. Sakata
Journal: Journal of Clinical Oncology (2009)

e15627 Background: S-1 plus cisplatin is considered to be the standard chemotherapy for Japanese patients with advanced gastric cancer (AGC) according to the results of three phase III trials (JCOG9912/SPIRITS/TOP-002). However, since few patients with poor performance status (PS2) were included in these phase III trials (27 of 1317; 2%), the standard treatment of patients with PS2 has not been established yet. In also, the characteristics and prognosis of AGC patients with PS2 has not been reported in detail. Methods: We retrospectively analyzed 545 patients with AGC treated by chemotherapy during the period from January 2003 to June 2008. Patients characteristic and treatment results were compared between PS0–1 and PS2. Results: At the beginning of 1st-line chemotherapy, PS0–1/2/3–4 was 454/69/22 cases respectively. Patients with peritoneal/pleural dissemination was more common in PS2 than PS0–1 (75% vs. 43%, p&lt;0.001). Patients with multiple metastatic places was more common in PS2 (62% vs. 43%; p=0.007). Fewer patients in PS2 were registered in clinical trial (1.4% vs. 25%, p&lt;0.001). First-line chemotherapy using oral drug (S- 1/capecitabine) was significantly fewer in PS2 (43% vs. 75%, P&lt;0.001). Median time to treatment failure was significantly shorter in PS2 (2.3 months vs. 4.2 months, p&lt;0.001). Patients who could receive second-line chemotherapy were significantly fewer in PS2 (50% vs. 75%, p&lt;0.001). With the median follow up time of 42 months, median survival time of patients with PS0–1 was 14.8 months (95% CI;13.1–16.5) and that of patients with PS2 was 6.1 months (4.3 to 7.4 months; hazard ratio for death 3.0: 95% CI2.3–4.0; p&lt;0.001). Mortality rate within 30 days was higher in PS2 (3% vs. 0.2%; p&lt;0.001). Conclusions: AGC patients with PS2 had not only had poor prognosis compared with PS0–1 but also had fewer chance of registration in the clinical trial, shorter time to treatment failure, and higher mortality rate within 30 days. Considering these different characteristics and treatment results of PS0–1 and PS2, clinical trial especially targeting AGC patients with PS2 is necessary to evaluate optimal chemotherapeutic regimens for PS2 patients. No significant financial relationships to disclose.
Liposomally-encapsulated cisplatin (Lipoplatin) plus gemcitabine in NSCLC: Preliminary results of a phase II trial and its antiangiogenesis potential
Authors: T. Boulikas, I. Mylonakis N, Athanasiou A, Kosmas C, Angel J
Journal: Journal of Clinical Oncology (2008)

19024 Background: Liposomally-encapsulated cisplatin (Lipoplatin) nanoparticles evade immune surveillance, target tumor cells in mouse xenografts, primary human tumors and metastases in patients as well as endothelial cells of tumor vasculature. Thus, Lipoplatin may enjoy the cytotoxic properties of cisplatin while additionally exerting antiangiogenic effects. Lipoplatin-gemcitabine is less toxic yet at least as efficacious as cisplatin-gemcitabine in Phase III trials. Lipoplatin has an orphan drug status for pancreatic cancer in the EU. This is the first report of a multicenter, phase II Lipoplatin study in NSCLC. Methods: Eligibility criteria included confirmed diagnosis of inoperable/metastatic NSCLC, no previous chemotherapy, WHO PS 0–1, adequate end-organ function. Patients received Lipoplatin 120 mg/m2 D1,8,15 combined with gemcitabine 1 g/m2 D1,8, in 3-week cycles, with disease evaluation after 3 and 6 cycles. Primary endpoints were Response Rates and Toxicity; OS PFS and QOL are also being evaluated. Results: 47 patients (pts) were treated; 41 were evaluable. There were 15 (36.6%) pts. with PR, 14 (34.1%) pts. with SD and 12 (29.3%) pts. with PD. Thus, Lipoplatin may be superior to historical platinum-gemcitabine combinations in NSCLC. Observed Toxicities were: grade 1–2 myelotoxicity; mild gastrointestinal toxicity in 50% of the pts. (easily controllable with antiemetics); hypersensitivity reactions in 7 pts (yet without hospitalization needs or any life threatening events); grade 1 nephrotoxicity in 18 (38.3%) pts (mostly in single infusions); of the 3 pts developing grade 2 nephrotoxicity, 2 did so after the first treatment, to recover with adequate hydration shortly after (no Grade 3 or 4 nephrotoxicity was seen; Neurotoxicity, a major side effect of cisplatin, was observed in 6 (12.8%) pts. and was mild (grade 1). None of the cases required treatment discontinuation. There were no associated deaths, or life-threatening adverse events. Conclusion: Lipoplatin may have lower toxicity as well as higher efficacy than cisplatin, when combined with gemcitabine in advanced NSCLC. Particularly relevant is that Lipoplatin is administered without pre- or post-hydration or on an outpatients basis. No significant financial relationships to disclose.
The influence of body mass index (BMI) on outcome in patients with advanced germ cell tumors (GCT)
Authors: D. J. Vaughn, M. Powell, P. J. Catalano, P. Loehrer, C. Nichols, C. Sweeney, G. Wilding, R. S. Dipaola
Journal: Journal of Clinical Oncology (2006)

14594 Background: Obesity is associated with increased mortality in a variety of cancers. Using data from ECOG 3887, a phase III study comparing cisplatin, etoposide, and bleomycin or ifosfamide in advanced GCT, we explored the prognostic significance of BMI. Methods: From 10/87 to 4/92, 286 assessable patients (pts) were enrolled in the original study. 1 pt was ineligible, 3 pts were missing weight/height; 282 pts are included in this analysis. BMI was computed by dividing weight by square of height (kg/m 2 ), and was categorized as underweight (&lt; 18.5), normal (18.5–24.9), overweight (25–29.9) and obese (&gt;30). A favorable response was defined as CR, NED post-surgery, or PR for ≥ 2 years. Fisher’s Exact Test was used to examine associations between BMI and favorable response. The Kaplan-Meier method was used to estimate overall survival by BMI. Proportional hazards models were used to examine the effect of BMI on survival after adjusting for International Stage (IS) and performance status (PS). As BMI was distributed similarly between the two treatment arms and no treatment differences were observed in the primary analysis, data from both arms were pooled to maximize power with regard to BMI. Results: Fifteen pts (5%) were underweight, 171 (61%) normal, 75 (27%) overweight, and 21 (7%) obese at study entry. The favorable response proportion was 53%, 67%, 51%, and 65%, respectively, for underweight, normal, overweight and obese pts. There was no association between BMI category and favorable response probability (chi square p = 0.08). 5-year survival for underweight, normal, overweight, and obese pts was 60%, 73%, 62%, and 67%, respectively. There was no difference in overall survival associated with BMI category (logrank p = 0.28), although statistical power is limited since there were few underweight/obese pts. After adjusting for IS and PS, there remained no association between overall survival and BMI category (hazard ratio per unit BMI 1.01, 95% CI 0.97–1.06). Conclusions: We observed no association between BMI and outcome, but statistical power is limited due to the small number of underweight and obese pts. No significant financial relationships to disclose.
Assessment of the heat shock protein 90 (HSP90) inhibitor IPI504 alone or in combination with the tyrosine kinase inhibitor (TKI) imatinib in mice carrying xenografts of human gastrointestinal stromal tumors (GIST)
Authors: P. Schoffski, G. Floris, R. Sciot, C. Stefan, A. Wozniak, K. Machiels, E. Normant, M. Debiec-Rychter
Journal: Journal of Clinical Oncology (2009)

10534 Background: Inhibition of HSP90 is a new strategy for treatment of GIST. IPI-504 is a potent i.v. HSP90 inhibitor. We assessed the activity of IPI-504 in imatinib-sensitive GIST xenografts, alone/combined with the TKI. Methods: Human GIST882 cells (KIT exon 13 mut.) were grafted in 43 nude mice, who were randomized to 4 groups: A (n=13; control); B (n=18; IPI-504 100 mg/kg 3x/wk p.o.); C (n=8; imatinib 50 mg/kg 2x/d p.o.); D (n=4; IPI-504+imatinib, dose/schedule as above) for 2 weeks. Histopathological assessment was done by H&amp;E and KIT immunostaining, histological response (HR) was defined by magnitude of necrosis and myxoid degeneration [grade 1 (0–10%), 2 (&gt;10% - ≤ 50%), 3 (&gt; 50% - ≤90%), 4 (&gt;90%)]. Expression/activation of KIT and its signaling (AKT, S6, MAPK) was assessed by Western blot. Results: IPI-504 alone significantly reduced tumor volume (41%) at day 14, further enhanced by adding imatinib (58%). Imatinib alone led to only a 5% reduction. IPI-504 induced grade 2 HR in 17/36 tumors, while the majority of tumors (13/15) treated with imatinib showed grade 1 HR. Grade 3/4 HRs were only seen with the combination. Mitosis decreased 3.3-fold, apoptosis increased 1.3-fold with IPI-504. Despite substantial reduction in mitotic activity in C and D (8.2- and 82-fold), apoptosis was virtually unaffected. In the IPI-504 arm, KIT levels were partially downregulated. Imatinib alone had no effect on KIT expression, while the combination produced a marked suppression of total KIT, accompanied by complete downregulation of the signaling. Loss of KIT in the combination arm was confirmed by immunostaining. Although KIT was not completely degraded with IPI-504, measurable effects on activation of AKT, S6 and MAPK were observed. Conclusions: IPI-504 has consistent antitumor effects in GIST xenografts, both histologically and on the molecular level. Combining IPI-504 with imatinib substantially enhances anti-tumor activity, providing a strong rationale for clinical trials of IPI-504 in GIST as single agent and in combination. [Table: see text]
A technique to quantify cytoreduction in the bone marrow induced by cytotoxic chemotherapy.
Authors: M S Blumenreich, A Strife, B D Clarkson
Journal: Journal of Clinical Oncology (1983)

A technique to quantify the cytoreduction in the bone marrow induced by chemotherapy in leukemia patients is reported. Bone-marrow core biopsies are obtained and the specimens are carefully minced in McCoy's 5a medium with a 20% fetal bovine serum supplement. The number of cells present per millimeter length of bone-marrow specimen is obtained by finding the concentration of cells in the supernatant, multiplying by the total volume of the supernatant, and dividing by the length of the bone-marrow biopsy specimen. Cytocentrifuge preparations are made from this supernatant and stained by standard techniques. Once the percentage of blasts is found, the absolute number of blasts per millimeter of bone marrow can be calculated. Serial measurements were made in 19 patients: nine patients were receiving first-line therapy for acute nonlymphocytic leukemia, and 10 were given experimental chemotherapy, which consisted of prolonged infusions of thymidine and cytosine arabinoside in six, and short infusions of thymidine, cystosine arabinoside, and phosphonoacetyl-l-aspartate, daily for five days in four. No patient with less than 2 log10 reduction in the number of marrow blasts achieved a remission, while only one patient in whom there was more than a 2 log10 reduction in the number of blasts failed to do so.