tbuckley/cabot-search huggingface dataset:
Relationship of sensory symptoms and motor function in patients with chemotherapy-induced peripheral neuropathy (CIPN) utilizing the EORTC QLQ CIPN20: NCCTG study N06CA
Authors: S. L. Wolf, R. Qin, D. L. Barton, J. A. Sloan, H. Liu, N. K. Aaronson, D. V. Satele, N. B. Green, B. I. Mattar, C. L. Loprinzi
Journal: Journal of Clinical Oncology (2009)

9587 Background: CIPN is characterized by adjectives not covered directly by most common measures of pain and functional limitations. Possible descriptors include numbness, tingling and shooting/burning pain. A prospective neuropathy treatment trial provided data to explore the relationship between self-reported aspects of this symptom. Methods: Baseline EORTC QLQ CIPN20 data and NCI CTCAE V3.0 (CTC)neuropathy grade (I-IV) were provided for all patients on trial. Spearman correlation coefficients and Kappa's coefficients of agreement were calculated between individual items and subscales of the CIPN20 as well as the CTC neuropathy scale. Simple regression models were applied to examine the association between the sensory symptoms and motor function in the fingers/hands (F/H). 200 patients provided 80% power to detect a correlation coefficient of 0.20 with a 5% Type I error. Results: A majority of patients reported “quite a bit” to “very much” numbness (57%) or tingling (62%) in F/H compared to “a little” or “not at all” (numbness (43%), tingling (38%)) by the CIPN20. In contrast, only 13% of the participants had grade III/IV neuropathy determined by the CTC scale. Fewer patients reported the higher two levels of CIPN20-measured shooting/burning pain in F/H (20% “quite a bit” to “very much”). Numbness and tingling were highly correlated (kappa=0.56), while neither were in high agreement with shooting/burning pain (kappa= 0.05 (tingling) and 0.14 (numbness)). The CIPN20 sensory and motor subscales were significantly associated with each other (p&lt;.0001) but were not or only weakly associated with the CTC. Specifically, tingling, numbness, and shooting/burning pain were not associated with the CTC (R=0.16, 0.18 and 0 .11, respectively). Using the CIPN20, all three sensations; numbness, tingling and shooting or burning pain were strongly associated with motor function. Conclusions: The most common moderate to severe CIPN symptoms were numbness and tingling with shooting/burning pain being less common. Shooting/ burning pain appears to be a separate symptom experience from numbness and tingling. The CTC neuropathy grading scale appears to be less sensitive than the CIPN20 in picking up sensory symptoms. No significant financial relationships to disclose.
Age, gender, performance status and stage outperformed stage alone in predicting overall survival (OS) in patients with small cell lung cancer: A pooled analysis of 1,623 patients from the North Central Cancer Treatment Group
Authors: N. R. Foster, S. J. Mandrekar, S. E. Schild, G. D. Nelson, J. R. Jett, A. A. Adjei
Journal: Journal of Clinical Oncology (2007)

7723 Background: It is critical that we understand the impact of patient, tumor, and treatment-related factors on patient prognosis for the proper design and analysis of Small Cell Lung Cancer (SCLC) trials. An analysis of 15 SCLC trials was performed to investigate and improve our understanding of several factors on OS. Methods: Data from 1623 patients (pts) were used. Age, gender, performance status (PS), tumor stage, body mass index (BMI), creatinine levels, hemoglobin levels, white blood cell counts (WBC), platelet counts, and bilirubin levels were tested for prognostic significance for OS both univariately and multivariately using a Cox Proportional Hazards Model. Models were stratified by protocol, and analyses carried out on the complete data available based on the selected covariates. Model discrimination (i.e., ability to discriminate patients with different survival times) was evaluated using the concordance index (COI). Results: Median follow-up was 63.1 months (range: 1.9 to 155.7). 58% and 42% of pts had extensive-stage or limited-stage SCLC, respectively. Patients with extensive-stage disease, PS&gt;0, increased age, and male gender had significantly worse OS both univariately and multivariately. Patients with increased WBC had significantly worse OS univariately, however, WBC was not a significant predictor when adjusted for other factors. None of the other factors were prognostic for OS. Model discrimination improved by 6.3% when age, gender, PS, and stage were included in a model compared to a model with stage alone (COI improved from 0.63 to 0.67). Conclusions: Age, gender, PS and stage did better at predicting OS than stage alone. Further refinement of this model, including the addition of number of metastatic sites at baseline and treatment related factors, is currently underway. No significant financial relationships to disclose. [Table: see text]
Genetic and proteomic features associated with survival after treatment with erlotinib in first-line therapy of non-small cell lung cancer
Authors: J. M. Amann, J. Lee, H. Roder, J. Brahmer, J. Schiller, D. P. Carbone
Journal: Journal of Clinical Oncology (2009)

8089 Background: An improved understanding of molecular features of cancers and cancer patients associated with benefit from targeted therapies could allow the rational personalization of therapies to increase the probability of efficacy and decrease toxicity and cost. Multiple biomarkers have been proposed for predicting benefit after therapy with EGF receptor targeted therapies in first line colon and second line lung cancer therapy. Methods: In this study, we analyzed available tumor and serum samples from ECOG 3503, a single arm phase II study of erlotinib in first line lung cancer, for mutations in Kras and EGFR, as well as the previously described serum MALDI proteomic classifier (Veristrat). Out of 137 enrolled patients, there were 93 serum samples and 43 tumor samples available. Results: Molecular analysis of a subset of tumors from patients enrolled in ECOG 3503 shows that 10/43 (23%) contained Kras mutations and 3/43 (7%) harbored EGFR mutations. Classification of the 93 available sera for the pattern of proteins previously published as associated with survival after treatment with gefitinib identified 68/93 (73%) as predicted to be “good” and 25/93 (27%) predicted to have poor survival. Of the 6 responders with available serum, 5 were classified as MALDI good. Correlation with survival demonstrated a highly statistically significant correlation with MALDI status (p &lt; 0.001), and a marginally significant association of EGFR mutation with survival (p = 0.05), but no correlation with ras mutation status. Median survival was 10.8 months in MALDI good patients and 3.9 in MALDI poor patients. MALDI status was independent of both ras and EGFR mutation status. Conclusions: Thus, in distinct contrast to colon cancer, ras gene mutations do not appear to be associated with survival after first line EGFR-targeted therapy in lung cancer. The previously defined MALDI predictor is potent and highly clinically significantly associated with survival after first line treatment with erlotinib, and is independent of mutations in ras and EGFR in this dataset. [Table: see text]
Gemcitabine (G), Ifosfamide (I), Vinorelbine (N) in advanced non-small cell lung cancer (NSCLC): A phase II study
Authors: J. F. Morère, M. C. Pailler, P. Saintigny, J. M. Bréchot, F. Morin, D. Mir, A. Martinez, J. L. Breau
Journal: Journal of Clinical Oncology (2004)

7357 Background: Toxicity is still a major problem with platinum-based doublet combinations used in the chemotherapy of advanced NSCLC. We already reported an encouraging activity of the combination of vinorelbine plus ifosfamide, with less toxicity than platinum-based regimens. In the present study, we assessed a triplet combination of gemcitabine plus ifosfamide plus vinorelbine (GIN) in chemotherapy-naive patients with stage IIIB/IV NSCLC and PS ≤ 2. Methods: GIN (day 1 and day 15: i.v. gemcitabine 1000 mg/m2 and vinorelbine 25 mg/m2; day 1 to day 3: i.v ifosfamide 1500 mg/m2 i.v. with mesna) was administered at 3 week-intervals for a maximum of 6 cycles. Patients were monitored for tumor response (CT scan) and toxicity. Results: Mean age of the 30 patients included was 60 (40–72) years. Median number of cycles per patient was 4 (1–6). Most frequent side effects were grade 3–4 neutropenia (43% of patients; febrile neutropenia in 3%), grade 2 asthenia (42%), moderate nausea-vomiting (14%) and grade 2 constipation (7%). No toxic deaths occurred. Partial response was observed in 9 (33%; CI 24–42 %) of 27 evaluable patients, stable disease in 8 (29 %), and progressive disease in 10 (37%). Survival rates at 1 and 2 years were 49% and 33%, respectively, and median survival 10.8 months. Conclusions: In advanced NSCLC, adding a third drug to platinum-based chemotherapy doublets has failed to improve the response and survival rates, while resulting in increased toxicity. In contrast, the addition of gemcitabine to the nonplatinum doublet ifosfamide plus vinorelbine may be a well-tolerated outpatient regimen. Median survival was equivalent to that reported using platinum-based chemotherapies. Modification of the administration schedule might increase the response rate, thus providing a valuable alternative to the more toxic platinum-based regimens. No significant financial relationships to disclose.
A multi-center, open-label study to evaluate the safety and efficacy of pentostatin, cytoxan, and rituxan (PCR) in the treatment of previously untreated or treated, stage III or IV, low-grade B-cell non-Hodgkin lymphoma (NHL) or bulky stage II lymphoma
Authors: N. P. Christiansen, R. Mena, Y. Markan, L. Pandit
Journal: Journal of Clinical Oncology (2007)

8071 Background: The decision to treat indolent B-cell NHL is often based on progressive disease, worsening symptoms, and increasing hematological variations. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with these agents, pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, represents a promising approach in the treatment of these patients. Most regimens have utilized fludarabine (F) as the purine analog but the myelosuppression and immunosuppression of (F) combinations frequently results in severe infections. Methods: Eligibility criteria allow previously treated and treatment-naïve patients diagnosed with bulky stage II or low-grade stage III/IV NHL (REAL classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m 2 ), C (600 mg/m 2 ), and R (375 mg/m 2 ) on day 1 of a 21-day cycle for a total of up to 10 cycles. Clinical evaluation was performed after cycles 2, 4, 6 and 8 and 10 (if necessary). Results: The intent-to-treat (ITT) population consisted of 87 NHL patients (median age 62.5, range 29–84) who received a total of 476 cycles (median 6 per patient). The ECOG status was 0 (62.4%), 1 (37.6%) and 2 (0%). The overall response rate of the 80 evaluable patients was 72.5% (CR 11.3%, Cru 12.5%, PR 48.8%). 14 cases of grade 4 and 17 cases of grade 3 neutropenia were documented. There were a total of 4 deaths due to acute myocardial infarction, NSCLC, a suspected cardiac event and 1 unknown cause of death. Conclusions: This immunochemotherapeutic regimen is active in indolent Grade III/IV NHL and the incidence of significant toxicities was low. Future trials evaluating the use of rituximab as maintenance therapy following this PCR regimen may also be warranted with a future goal towards possibly increasing the overall survival of patients with NHL. The presented results are preliminary and the study is currently on-going. No significant financial relationships to disclose.
Analysis of prognostic factors in patients with advanced pancreatic cancer: Subgroup analysis of a randomized phase III trial comparing single-agent gemcitabine to the gemcitabine plus cisplatin combination
Authors: S. Boeck, A. Hinke, R. Wilkowski, V. Heinemann
Journal: Journal of Clinical Oncology (2005)

4105 Background: The combination of gemcitabine (Gem) and cisplatin (Cis) has shown promising activity in several phase II and III trials in the treatment of patients with advanced pancreatic cancer. While in a previously reported phase III trial (Heinemann V et al, Proc ASCO 22: # 1003) the Gem+Cis regimen (arm A) showed only a trend towards a superior overall-survival (OS) as compared to single-agent Gem (arm B), there might be subgroups of patients that more clearly benefit from combination therapy. Methods: This phase III trial enrolled 195 patients with histologically proven advanced pancreatic adenocarcinoma to receive either Gem+Cis or Gem alone. Subgroup analyses were performed to evaluate the impact of treatment, Karnofsky performance status (KPS) and other prognostic factors on OS and progression-free survival (PFS). Treatment differences between the subgroups were analysed by the Kaplan-Meier method, the log-rank test and the Cox model. Results: Median OS was 225 days (d) in arm A and 181 d in arm B, respectively (p=0,15). Data of 160 patients were available for this subgroup analysis. In univariate as well as multivariate analysis, KPS determined at the time of randomisation was the strongest prognostic factor for median OS (KPS 70–80%: 143 d vs. KPS 90–100%: 270 d, p=0,0006) and for PFS (KPS 70–80%: 86 d vs. KPS 90–100%: 162 d, p=0,0043). In the subgroup with a good KPS (90–100%) median OS was 322 d for patients treated with Gem+Cis and 206 d for treatment with Gem alone (p=0,051). Median OS for the subgroup Gem/KPS 70–80% was 143 d and for Gem+Cis/KPS 70–80% 147 d, respectively (p=0,64). Conclusion: In this randomized phase III trial, patients with a good KPS (90–100%) appeared to benefit from the more intensive combination therapy Gem+Cis and a had a considerably longer median OS as compared to patients treated with gemcitabine alone. By contrast, in patients with a poor KPS (70–80%) no survival benefit was observed when Gem alone was compared to the combination therapy with Gem+Cis. This observation should be included into the design of future trials on combination therapy of pancreatic cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Germany Lilly Germany
Dose escalating trial of 17-AAG with bortezomib (BZ) in patients with relapsed refractory multiple myeloma (MM)
Authors: A. Chanan-Khan, M. Alsina, M. Carroll, B. Landrigan, D. Doss, M. Albitar, C. Mitsiades, G. F. Cropp, A. L. Hannah, P. G. Richardson
Journal: Journal of Clinical Oncology (2005)

6682 Background: In vitro, 17AAG (a benzaquinoid ansamycin) inhibits HSP90, reducing cellular levels of oncoproteins such as Raf-1, HER2, mutant p53, IL-6 and IGF-R1. Disruption of these heteroprotein complexes results in their decreased stability and impaired cellular trafficking. Single-agent 17AAG shows in vitro activity against MM cells from patients resistant to BZ. BZ induces apoptosis of p53 wild-type and p53 mutant MM cells, reverses resistance to apoptosis in MM cells conferred by IL-6; BZ also decreases adherence of MM cells to bone marrow stromal cells (BMSCs) and NFkB-dependent induction of IL-6 secretion in BMSCs. Non-clinical in vivo safety studies of the combination of 17-AAG and BZ showed possible additive hepatotoxicity. Treatment of MM cells with BZ triggered significant Hsp90 up-regulation as a stress response in MM cells; 17AAG blocks this stress response, thereby markedly enhancing MM cell sensitivity to BZ. Methods: Study objectives define the recommended dose of each agent when given in combination, to determine the pharmacokinetics (PK) of 17AAG and its active metabolite, to evaluate biological activity of 17AAG + BZ (proteasome 20S in PBLs; apoptosis, changes in HSP70/90, pAKT and expression of IL-6R and IGF-R1 in MM cells). Pts receive IV therapy twice weekly for 2 out of 3 weeks; 17AAG (denoted KOS-953 in a Cremophor-based formulation) is administered at 100 mg/m2 over 1 hour; BZ follows as IVB at doses of 0.7 and 1.0 mg/m2. Escalation of both agents is planned. Results: 4 pts (2F; median age 56 yrs; KPS 80; prior regimens 3, range 3–4) were enrolled in 2 dose levels. Dose limiting toxicity has not been observed to date. Drug-related toxicity (Grade 1–2): diarrhea, nausea, fatigue and infusional reactions. Bone marrow aspirates showed evidence of increased apoptosis on day 11 as measured by Annexin V, with reduced expression of IL-6R on the surface of CD138+ plasma cells. PK and proteasome data will be presented. One pt treated at the 1st dose level showed decreased size of palpable plasmacytoma. Conclusions: Dose escalation continues to define the dose of 17AAG when administered with BZ. Combination of two targeted therapies may hold promise in the treatment of refractory myeloma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Kosan Biosciences Kosan Biosciences Kosan Biosciences
Impact of preradiation versus postoperative MRI changes in T1w contrast enhanced and FLAIR images on radiation treatment planning
Authors: J. O. Blakeley, K. Redmon, E. Ford, E. Dunbar, K. Singh, M. Armour, S. A. Grossman, L. Kleinberg
Journal: Journal of Clinical Oncology (2008)

2046 Background: Radiation therapy (XRT) treatment plans are based on MRI signal changes on FLAIR and T1w contrast enhanced (CE) images. Often the MRI used for this planning is obtained post-operatively (post-OP). XRT does not generally start until >14 days later. We explored the frequency of changes from the post-OP to the pre-XRT period and how those changes impact XRT planning. Methods: Records of all adults with newly diagnosed HGG (glioblastoma multiforme, anaplastic astrocytoma or anaplastic oligodendroglioma) who received post-OP and additional pre-XRT MRIs at Johns Hopkins from 1/05 to 1/07 were reviewed. The MRIs of patients with increased T1w CE or FLAIR abnormality on the pre-XRT MRI were co-registered in the Pinnacle treatment planning system v.8.0 (ADAC/Philips Inc, Madison, WI). Gross tumor volumes (GTV) were delineated based on CE and FLAIR abnormality. Clinical target volumes (CTV) were generated using an isotropic 1cm expansion of the GTV and planning target volumes (PTV) representing the treatment target were generated using a 0.3cm expansion. Results: 37 patients with newly diagnosed HGG with post-OP CE and pre-XRT CE MRIs were identified; 15 were excluded for incomplete data. 22 cases were reviewed and10 patients (45%) had increased T1w contrast enhancement, FLAIR signal abnormality or both on the pre-XRT MRI versus the post-OP MRI. There was no difference in mean age (56 v. 55 years), time between the post-OP and pre-XRT MRI (21 v. 19 days), gender (8 v. 5 men), or histology (10 v. 8 GBM) between patients with or without changes on MRI. Steroid dose was not significnatly different between groups. The average PTV post-OP was 453 + 157cm3 and pre-RT was 488 + 228cm3. In all ten cases, there was measureable volume of non-overlap (area included in planning based on pre-XRT MRI and not included based on post-OP MRI) ranging from 14–277cm3 (x=91 + 81cm3). Conclusions: Changes on MRI between post-op and pre-XRT evaluations occurred in nearly half of the patients (45%) in this small series. The etiology of these is not known and deserves further investigation. If the changes reflect tumor progression, potentially important tumor volumes may be missed in the XRT ports if the post-op MRI is relied upon for treatment planning. No significant financial relationships to disclose.
A Novel Immunohistochemical Sequential Multi-Labelling and Erasing Technique Enables Epitope Characterization of Bone Marrow Pericytes In Primary Myelofibrosis
Authors: Ann Brinch Madelung, Michael Bzorek, Henrik Bondo, Eva M.K. Zetterberg, Ole Weis Bjerrum, Hans Carl Hasselbalch, Stefan Scheding, Elisabeth Ralfkiaer
Journal: Blood (2010)
An analysis of the prognostic value of handgrip strength and its incorporation into the comprehensive geriatric assessment (CGA) in elderly Asian patients with cancer.
Authors: R. Kanesvaran, K. N. Koo, W. Chen, D. Poon
Journal: Journal of Clinical Oncology (2011)

9093 Background: Handgrip strength has been shown to predict all cause mortality in several studies. The objective of our study was to assess the prognostic value of handgrip strength in an Asian geriatric oncology population and its integration into the comprehensive geriatric assessment (CGA). Methods: A prospective analysis of CGA data including handgrip strength was done on 249 newly diagnosed patients aged 70 years and above who attended the geriatric oncology clinic at the National Cancer Centre Singapore. Univariate and multivariate analyses were done using the Cox proportional hazard method to identify prognostic factors within the CGA and to analyze the relationship between handgrip strength (using a hydraulic hand dynamometer) and overall survival after controlling for age, ECOG performance status, gender, body mass index (BMI) and the DETERMINE nutritional assessment index. Results: Handgrip strength was significantly associated with overall survival (HR= 0.97, 95% CI, 0.97-0.99) in univariate analysis and remained significant when controlled for BMI, age, ECOG performance status, stage, gender and DETERMINE nutritional index individually. Multivariate analysis of the CGA factors revealed that only DETERMINE nutritional index poor risk (HR = 2.45, 95% CI, 1.33 – 4.53), ECOG performance status of 2 or more (HR = 2.52, 95% CI, 1.57 – 4.06) and advanced stage (HR = 3.09, 95% CI 1.47 – 6.50) were significant prognostic factors in our study population. Conclusions: Handgrip strength is an important prognostic factor in elderly cancer patients and should be incorporated in the comprehensive geriatric assessment (CGA) of such patients. The findings of DETERMINE nutritional index, ECOG performance status and advanced stage as prognostic factors within the CGA, confirm the findings of our prior retrospective analysis in a population of Asian elderly cancer patients.