tbuckley/cabot-search huggingface dataset:
Spirituality, religiosity, spiritual pain, and quality of life among caregivers of Latin American patients with advanced cancer: A multicenter study.
Authors: Marvin Omar Delgado-Guay, Alejandra Palma, Eva Rossina Duarte, Monica Grez, Laura Tupper, Diane D Liu, Andrea Octavia Ferguson, Hilda Cantu, Jewel Ochoa, Janet L. Williams, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

245 Background: Caregivers of cancer patients often face physical, and psychosocial hardship. The association between spirituality (S), religiosity (R), spiritual pain (SP), coping, and quality of life (QOL) have not been well characterized. The main purpose of this multicenter study was to determine these associations among LACs. Methods: We interviewed 319 LACs at palliative care clinics in Chile, Guatemala, and the US. LACs completed FICA (S/R assessment), ESAS–FS, PSWQ (worry), B-COPE/B-R-COPE (coping), and FACIT-Sp (spiritual well-being). Results: Median age 47 y, IQR=36, 59; 231 (73%) female, 207 (66%) married, 194 (61%) Catholic, 90 (28%) Non-Catholic Christian, 10 (3%) non-religious affiliation. Relationship: 111 (35%) spouses, 102 (32.5%) children, 31 (10%) siblings, 21 (7%) parents, and 59 (19%) others. 103 (32%) worked full-time, 38 (12%) worked-part-time, 96 (30%) homemaker, and 29 (9%) retired. 278 (92%) considered themselves moderately/highly spiritual and 75% moderately/highly religious, median: 8 (IQR: 6, 9) and 6 (4, 8) respectively. Median importance of S/R in their life was 10 (IQR: 7-10). The frequency and associations among the importance of S/R and different items were as follows: S/R is a source of strength and comfort (98%, r = 0.71; p &lt; 0.0001), helps them to cope with patients’ illness (98%, r = 0.65; p &lt; 0.0001). 44% of LACs reported that their spiritual/religious needs had not been supported by the medical team. 243/301 (81%) of LACs reported spiritual pain (median 6; IQR: 2-9). Spiritual pain significantly correlated with worse pain (r = 0.42, p &lt; 0.0001), fatigue (r = 0.34, p &lt; 0.0001), depression (r = 0.46, p &lt; 0.0001), anxiety (r = 0.48, p &lt; 0.0001), financial distress (r = 0.36, p &lt; 0.0001), well-being (r = 0.3, p &lt; 0.0001), worry (r = 0.42, p &lt; 0.001), denial (r = 0.3, p &lt; 0.0001), behavioral disengagement (r = 0.3, p &lt; 0.0001), FACIT-sp (r = -0.18, p = 0.002), negative religious coping (r = 0.35, p &lt; 0.0001). Conclusions: LACs report high level and importance of S/R in dealing with the patient’s illness and low level of S/R support from clinicians. 81% of LACs expressed spiritual pain that impacts their own symptoms, coping, and QOL. More research is needed.
Effect of sorafenib on protein expression profiles in melanoma.
Authors: B. Seliger, A. Mueller, K. Schulz, F. Leich
Journal: Journal of Clinical Oncology (2011)

e13530 Background: Advances in the understanding of genetic alterations associated with the development of melanoma resulted in the implementation of promising novel agents that inhibit specific signal transduction pathways. Sorafenib, a multimeric inhibitor of the RAF/RAS/MEK pathway has antitumor activity in melanoma patients when used in combination with other chemotherapeutics. Methods: After studying the influence of sorafenib on the growth properties of different melanoma cell lines, we determined sorafenib-induced changes within the protein expression pattern of these cell lines using 2DE proteome-based analysis. Results: Sorafenib affects growth properties of melanoma cell lines in a dose dependent manner. This was also associated with a differential expression of > 100 proteins as determined by 2DE proteome-based analysis followed by mass spectrometry of untreated versus sorafenib-treated melanoma cells. The proteins identified were categorized according to distinct protein families and cellular localizations. In particular proteins involved in metabolism, signal transduction and in cytoskeletal formation have been detected. The differentially expressed proteins were validated by RT-PCR and Western blot analysis using a large panel of melanoma cell lines as well as by immunohistochemistry of melanoma lesions using a tissue micro array. Furthermore, mutations in B-RAF and kit were determined and associated with the response to sorafenib in the treated melanoma cells. Conclusions: These results suggest that the treatment of melanoma cells with sorafenib has not only altered the protein expression pattern, but has also an impact on their growth property and phenotype. Therefore a number of these differentially expressed proteins could be used as biomarker from monitoring of drug sensitivity of melanoma cells.
Contribution of polypharmacy and potentially inappropriate medication use to inferior survival in older patients with aggressive lymphoma.
Authors: Richard Jirui Lin, Robin Guo, Daniel Jacob Becker, Michael L. Grossbard, Catherine S. Magid Diefenbach
Journal: Journal of Clinical Oncology (2016)

129 Background: Survival outcomes for older patients with aggressive non-Hodgkin’s lymphoma (NHL) are disproportionally inferior to those of younger patients. While differences in tumor biology may play a role, older patients are often frail with comorbidities, polypharmacy, and use potentially inappropriate medications (PIM). Methods: Using Cox proportional hazard and logistic regression models, we retrospectively analyzed all aggressive NHL patients age 60 and older diagnosed and treated at our institution from 2009-2014 to examine the effect of polypharmacy and PIM use on progression-free survival (PFS), overall survival (OS), and treatment-related toxicities. Results: We included 141 patients with evaluable data after excluding patients with incomplete record. The median age was 71 years. At the time of diagnosis, 44% of patients used more than 4 medications and 47% used at least one PIM. During first-line treatment, only 43% of patients received chemotherapy of adequate relative dose intensity (&gt;85% scheduled dose), and 63% experienced grade 3 or greater toxicities. Age, International Prognostic Index, and PIM use correlated with each other. Number of medications (p = 0.005) and PIM use (p &lt; 0.001) were associated with shortened PFS by log-rank test, and PIM use remained a strong independent predictor of PFS in multivariable analysis (HR 1.84, p = 0.005). Number of medications (p = 0.003) and PIM use (p = 0.009) were also associated with shortened OS by log-rank test, although only albumin level predicted OS in multivariable analysis. Most importantly, PIM use was strongly associated with grade 3 or greater toxicities in multivariable analysis (OR 7.4, p = 0.001). Conclusions: We report here for the first time adverse impacts of polypharmacy and PIM use in older patients with aggressive lymphoma. We suggest that drug-drug interactions may significantly impair the delivery of adequate chemotherapy dosage and increase toxicities thus resulting in inferior survival outcome. Our findings support the use of evidence-based geriatric and palliative care principles to guide meticulous medication management to eliminate outcome disparity in older lymphoma patients.
Breast cancer in young women (&lt;35 years): The impact of age on the prognosis
Authors: W. Bal, M. Jarzab, E. Nowara, M. Kowalski, M. Kustra, I. Cedrych
Journal: Journal of Clinical Oncology (2008)

619 Background: Breast cancer in women below 35 years of age occurs rarely (2–4% of all breast ca). Age below 35 is an independent risk factor of recurrence and death. The aim of the study was to assess the association of clinical and pathologic risk factors with outcome in women with breast cancer aged 35 years or less. Methods: The analysis was carried out in 194 patients (pts) with breast cancer aged 35 years or less, referred to our Clinic between 1997–2006. Among this group there were 19.7, 36.9, 37.7 and 5.7% pts in stages I- IV, respectively. Overexpression of estrogen and progesterone receptors was found in 52.1 and 46.9%; HER-2 overexpression was observed in 17.4%. In 17.2% positive breast cancer family history was noted. The clinical factors associated with disease-free survival time were assessed by Kaplan-Meier survival analysis and multivariate Cox regression. Results: Median time of follow-up was 38 months. Relapse occurred in 30.1% of pts (18.9% with distant metastases, 10.2% with local recurrence). 5-year recurrence-free survival was 56.8% (patients in stage I-III only). In univariate Kaplan-Meier analysis node status, positive HER2, negative ER/PR and age at diagnosis between 30–35 years were negatively affecting the prognosis (p<0.05). Patients between 30–35 vs. <30 years did not differ significantly in the disease stage, but ER/PR(-) and HER2(+) patients were more frequent in 30–35 yr group. In multivariate analysis, node status and negative hormone receptor status were significantly associated with survival time (with hazard ratios 2.7 and 2.1, respectively), while the increase of risk related to age between 30–35 years was increasing the risk of relapse by factor 1.7 (p=0.09). Conclusions: Age below 30 years and positive receptor status delineate a group of young patients with better prognosis. It shall be further analyzed while age of the patient independently affects the outcome of therapy. No significant financial relationships to disclose.
Long-term response to sunitinib for metastatic renal cell carcinoma (mRCC) patients treated on clinical trials at Memorial Sloan-Kettering Cancer Center.
Authors: A. M. Molina, X. Jia, M. S. Ginsberg, S. Velasco, D. R. Feldman, S. Patil, R. J. Motzer
Journal: Journal of Clinical Oncology (2011)

4615 Background: Sunitinib has significant activity in pts with mRCC. We report long-term responders, defined as pts achieving ongoing complete response (CR) or remaining progression-free for > 18 months on sunitinib. Methods: 186 pts were treated with sunitinib alone or in combination on 9 clinical trials; all had >2 years of follow-up from sunitinib start to analysis. Median progression-free survival (PFS) was 11 mos (95% CI 8-14); median OS was 27 mos (95% CI 21-35). 34 long-term responders were identified. Results: Characteristics for the 34 and the entire cohort of 186 were examined (Table). Best response for the 38 pts was CR in 1, partial response in 26, and stable disease in 7 pts. Average duration of sunitinib therapy was 30 mos (range 18.1-73.9 mos) and 3 pts remain on therapy. Following 18 mos progression-free on sunitinib, long-term responders had an additional median PFS of 25 mos (95% CI, 9-51 mos). Univariate logistic regression analysis identified bone metastasis (p=.08), lung metastasis (p=.02), and intermediate/poor risk groups (p=.05) as adverse prognostic factors for long-term response (Table). Conclusions: Sunitinib achieves long-term response in a subset of pts with mRCC. Lack of bone or lung metastases and good MSKCC risk may predict long-term response. All (N=186) Long-term responders (N=34) Univariate logistic analysis (yes vs. no) Odds ratio (95%CI) p value Sites of disease* Bone Lung Liver 50 (27%) 130 (70%) 40 (22%) 5 (15%) 18 (53%) 4 (12%) 0.41 (0.15, 1.12) 0.39 (0.18, 0.84) 0.43 (0.14, 1.29) 0.08 0.02 0.13 >2 metastatic sites* 139 (75%) 22 (65%) 0.53 (0.24, 1.19) 0.12 Prior treatment 73 (39%) 16 (47%) 1.48 (0.70, 3.14) 0.30 Clear cell histology 164 (88%) 31 (91%) 1.48 (0.41, 5.30) 0.55 MSKCC risk group Favorable Intermediate/poor 91 (49%) 95 (51%) 22 (65%) 12 (35%) 2.21 (1.02, 4.78) 0.05 * 1 pt missing
A randomized phase III trial of second-line chemotherapy comparing CPT-11 alone versus S-1 plus CPT-11 combination therapy in advanced gastric cancer refractory to first-line therapy with S-1 (JACCRO GC-05).
Authors: Kazuhiro Nishikawa, Kazuaki Tanabe, Masashi Fujii, Chikara Kunisaki, Akihito Tsuji, Nobuhisa Matsuhashi, Akinori Takagane, Tetsuro Ohno, Tomono Kawase, Mitsugu Kochi, Kazuhiro Yoshida, Yoshihiro Kakeji, Wataru Ichikawa, Keisho Chin, Masanori Terashima, Masahiro Takeuchi, Toshifusa Nakajima
Journal: Journal of Clinical Oncology (2014)

87 Background: In East Asia, S-1 + CDDP (SP) has been employed as first-line therapy for advanced gastric cancer (AGC) from the results of SPIRITS trial. Patients who were resistant to chemotherapy with S-1 in the first-line treatment were widely treated with taxane alone or CPT-11 alone as the second-line treatment. On the other hand, the response rate of combination therapy with S-1 is higher than that of CPT-11 alone. Then, we hypothesized that S-1 + CPT-11 prolongs survival in the second-line treatment comparing with CPT-11 alone after failure in the first-line treatment with S-1. (NCT00639327). Methods: Patients with AGC who confirmed disease progression by imaging after the first-line therapy with SP, S-1 + cocetaxel or S-1 alone except S-1 + CPT-11 were allocated into S-1 plus CPT-11 group (Group A) or CPT-11 alone group (Group B) as second-line chemotherapy. Patients who were relapsed to adjuvant chemotherapy with S-1 were not enrolled. Primary endpoint was overall survival, and secondary endpoints were progression free survival, response rate and adverse events. Results: From March 2008 to June 2011, 304 patients were enrolled, and 294 were eligible for analysis. The overall survival was 8.8 months (M) in the Group A and 9.4M in the Group B. There is no statistically significant difference in both groups (P=0.9156). The progression free survival was 4.8M in the Group A and 4.9M in the Group B (P=0.1568). The response rate was 7.6% in the Group A and 7.4% in the Group B. Grade 3 or higher leukopenia, neutropenia and febrile neutropenia were observed more frequently in the Group A than in the Group B. Conclusions: From our results, we do not recommend consecutive use of S-1 as second-line treatment in patients who are refractory to S-1 in first-line chemotherapy. Clinical trial information: 00639327.
Surveillance and evidence-based safety initiatives in radiation medicine.
Authors: Ajay Kapur, Louis Potters
Journal: Journal of Clinical Oncology (2014)

247 Background: Moving towards safer radiation medicine requires an active surveillance of associated failures, their causes and effects, and evidence-based approaches for mitigation. In this study, by using retrospective and prospective surveillance, we have implemented evidence-based risk mitigation strategies in our radiation medicine practice. Methods: Incident learning has shown us that failures occur due to delays or defects in the radiation medicine process and that cultural error-provoking conditions raise these risks. Our initiatives were directed towards mitigation of defects in the high-risk process steps identified through a planning process FMEA. These included the standardization of care pathways and grading scale for assessing toxicity; pre-planning contour, directive peer review; electronic whiteboard for planning coordination and incident reporting, a process interlock policy to thwart delay-rushed processes; and the use of 6 sigma metrics to monitor individual staff operational efficiencies. Results: There has been a 3-fold increase over a 9 month period in incident reporting relative to the previous 6 previous years, by the peer group historically least likely to report, with no increase in adverse events. Evidence-based care pathways have been used with under 5% clinical non-compliance rates. The implementation of contour and directive pre-planning peer review has enhanced early defect detection. There has been a twofold drop in the occurrence of high-risk procedural delays. Patient treatment start delays are routinely enforced on cases that would have historically been rushed. Temporal trends demonstrate over 30% improvement in process Z-scores over the past three years. Conclusions: Driving these risk mitigation initiatives has challenged traditional norms such as expediting treatment initiation in delay-rushed environments or sustaining care pathways that are more experience rather than evidence-based. Therefore their implementation has met with substantial barriers. It is the focus on patient safety, statistical process control, policy enforcement, regular incident reviews, and use of quantitative metrics that has been instrumental in realizing these changes and crossing barriers.
A phase I dose escalation study to evaluate safety and tolerability of cabazitaxel (Cbz) as a single agent in patients (pts) with advanced gastric adenocarcinoma who have failed prior chemotherapy (CT) regimens (GASTANA).
Authors: Yoon-Koo Kang, Baek-Yeol Ryoo, Shinkyo Yoon, Lin Shen, Jooyun Lee, Chenlu Wei, Yu Zhou, Min-Hee Ryu
Journal: Journal of Clinical Oncology (2014)

141 Background: Cbz showed antitumor activity in a CT-resistant human gastric cancer xenograft model. The Phase I GASTANA study aimed to determine the safety profile of Cbz in pts with advanced gastric adenocarcinoma who failed prior CT regimens. Methods: Asian pts with metastatic gastric adenocarcinoma failing 2 prior CT regimens received Cbz (single agent, Day 1 of every 3-week cycle) in a standard 3+3 dose escalation design. Dose levels (DL) were 20 mg/m 2 (DL 1), 25 mg/m 2 (DL 2) and 15 mg/m 2 (DL -1). Treatment continued until disease progression or unacceptable toxicity. Prophylactic G-CSF was not permitted at cycle 1. Results: Fifteen pts were evaluable for dose-limiting toxicities (DLTs) at cycle 1. All pts were heavily pretreated (median of 2 prior anticancer regimens), and 11 had prior taxane exposure.At DL 1, no DLTs occurred in any of the first 3 pts. At DL 2, 4 pts were enrolled as 1 pt discontinued prematurely, with only 1 DLT (Grade [Gr] 4 febrile neutropenia [FN]) observed. However, all 4 pts at DL 2 experienced FN, and so 3 more pts were enrolled at DL 1 to further explore safety at this lower DL. Two DLTs (Gr 4 neutropenia &gt; 7 days) occurred in these additional 3 pts. In response, DL -1 was opened, with no DLTs observed in the 6 pts enrolled. The median numbers of cycles were 5 (DL 1), 1.5 (DL 2) and 3 (DL -1). Frequent Gr 3/4 toxicities (safety population, N = 16) included neutropenia (63%) and FN (38%). Best overall responses included 1 partial response (6.3%; DL -1) and 8 stable disease (50%). Conclusions: Due to the unexpectedly high incidence of neutropenia-related complications compared with pts with other cancer types, a further Phase II study of Cbz was put on hold pending further data in pts with gastric cancer. The frequent occurrence of neutropenic complications with Cbz in this study may be attributed in part to the heavily pretreated nature of the pts and the accumulated toxicity of prior taxane therapy. Also, prophylactic G-CSF use after cycle 1 was not mandatory in pts with dose interruptions due to neutropenia, which may have increased the rate of neutropenic complications in subsequent cycles. Clinical trial information: NCT01497964.
Parmacokinetics (PK) of oral vinorelbine (VNR) in association with pegylated liposomal doxorubicin (PLD) in metastatic ovarian carcinoma
Authors: M. Airoldi, L. Cattel, P. Milla, R. Passera, F. Pedani, A. Crova
Journal: Journal of Clinical Oncology (2008)

13531 Background: The VNR-PLD association proved to be an effective therapy in the treatment of metastatic ovarian carcinoma. The advantages of VNR oral formulation are the ease of administration and the reduced need for hospitalization. Previous results obtained by our group showed that the pre-administration of PLD before iv VNR raises its plasmatic levels, due to VNR reduced elimination rate. The aim of this work is to study the influence of PLD on the absorption and elimination phases of oral VNR and viceversa. Methods: 12 patients (21 cycles), affected by metastatic ovarian carcinoma, were randomized to receive oral VNR 60 mg/m2 and PLD 20 mg/m2 every 14d in one of the following schedules: VNR d1 and PLD d2 (arm A), VNR d1 and PLD d1 2 hours after VNR (arm B), PLD d1 and VNR d1 immediately after PLD (arm C). Pk parameters were evaluated by non-compartmental analysis, while statistical analysis was performed by Kruskal Wallis test. Results: VNR median Cltot was reduced by PLD pre-administration (arm A vs. C: 513 vs. 274 l/h, p=0.066), while VNR AUCtot was increased (arm A vs. C: 161 vs. 430 ng*h/ml, p=0.113). It was also observed a VNR delayed Tmax (arm A vs. C: 1 vs. 2, p=0.202). On the other hand, PLD median t/2 was decreased by VNR pre-administration (arm A vs. C: 90 vs. 68 h, p=0.046). All the other pk parameters were unmodified. The trend for arm B is very similar to that found in arm A, both for VNR and PLD. Conclusions: Our data demonstrate that PLD pre-administration (arm C) can increase VNR bioavailability, as a consequence of its reduced clearance. Comparing to our previous VNR iv-PLD study, results are apparently similar but substantially different. In that case, the VNR reduced clearance was depending only on elimination rate constant reduction; in this case indeed, was not depending neither on elimination rate constant nor volume of distribution reduction. No significant financial relationships to disclose.
Phase III clinical trial evaluating low-molecular weight heparin (LMWH) in patients with advanced cancer: A North Central Cancer Treatment Group study
Authors: K. Sideras, P. L. Schaefer, S. H. Okuno, J. A. Sloan, L. Kutteh, T. R. Fitch, S. R. Dakhil, R. Levitt, P. J. Novotny, C. L. Loprinzi
Journal: Journal of Clinical Oncology (2005)

8186 Background: Several laboratory and clinical studies have suggested an antineoplastic role for anticoagulants. Low molecular weight heparin has been shown to have direct antigrowth, antiangiogenesis, and anti-metastatic effects in vitro. Retrospective clinical studies looking at treatment of venous thromboembolism have suggested a survival advantage for cancer pts treated with LMWH. The purpose of this study was to prospectively assess whether LMWH would provide a survival benefit in pts with advanced cancers. Methods: We performed a randomized prospective placebo-controlled stratified study with 138 pts. Eligibility criteria included advanced cancer, physician-judged life expectancy more than 12 weeks and ECOG performance status of 0–2. Pts were stratified according to age, gender, disease site, prior thrombotic episodes, prognostic index scores and concurrent therapy. Initially the study was double blinded and placebo controlled with the pts receiving either daily injections with 5,000 units of LMWH (dalteparin) or saline. However, due to low accrual midway through the study (50 pts), the placebo injections arm was dropped and the study became open labeled with pts receiving either LMWH injections or standard clinical care. The primary endpoint of the study was overall survival. Planned accrual was 265 pts per study arm but the protocol accrual was stopped early by a pt monitoring committee. The final sample size provided 46% power to detect a 50% improvement in median survival times. Results: Of 138 pts, 68 received LMWH and 70 did not. The Kaplan-Meier survival estimates for the first, second and third years were 38%, 12% and 0% for the LMWH arms and 40%, 13% and 7% for the control arms (p=0.46, Log-Rank test). Median survival times were 222 days on the LMWH arms and 319 days on the control arms. The rate of severe or worse venous thromboembolism was 6% (4/68) in the LMWH arms and 7% (5/70) in the control arms (p=0.99). The rate of severe or worse bleeding was 4% (2/68) in the LMWH arms and 7% (5/70) in the control arms (p=0.46). Conclusion: This trial was unable to demonstrate any survival benefit for LMWH in pts with advanced cancer. No significant financial relationships to disclose.