tbuckley/cabot-search huggingface dataset:
A prospective evaluation of radiotherapy (RT) related skin reactions in a multi-racial/ethnic population of women with newly diagnosed breast cancer (BC).
Authors: James John Urbanic, Doug Case, Luis Baez-Diaz, Doris R. Brown, Jon Strasser, Gina Enevold, Michelle Naughton, Kathryn E Weaver, Kathy Baglan, David Bryant, Carl Langefeld, Thomas E. Lad, Lucille Lee, Grant Rine, Amarinthia E. Curtis, Christoper D. Koprowski, W. Vic Tomlinson, Glenn Jay Lesser, Edward G. Shaw, Jennifer J. Hu
Journal: Journal of Clinical Oncology (2015)

6593 Background: RT-related early adverse skin reactions (EASR) are common in BC patients. EASR occur during/within 2 months post-RT. Predictive biomarkers for EASR are under active investigation. Previous studies have limited sample size/lack racial/ethnic diversity. This study designed to evaluate disparities in EASR of a multi-racial/ethnic BC population. Methods: Stage 0-III BC patients. Inclusion criteria: RT dose > 40 Gy and daily RT 1.8 to 2.7 Gy/fx. Regional nodal irradiation, mastectomy/lumpectopmy, concur/sequent boost, chemotherapy, hormonal therapy allowed. Exclusion criteria: immediate reconstruction, partial breast RT. Primary outcome: EASR (Oncology Nursing Society (ONS) acute skin toxicity (0-6 scale)) assessed during/2 months post-RT. Mixed effects repeated measures analysis of variance used to assess race/ethnicity and mastectomy/lumpectomy differences in EASR over time. Results: 10/2011-6/2013, 1000 patients accrued (405 non-Hispanic white (NHW), 277 non-Hispanic black (NHB), 241 Hispanic, 62 Asian/Pacific Islanders, 15 other). Both time by race/ethnicity and time by mastectomy interactions statistically significant (p < 0.001 & p = 0.008, respectively). Based on race/ethnic cohorts, significant differences in patient characteristics (p < 0.05) existed for age, BMI, marital status, education, health insurance, cancer stage, and medical comorbidities. Mean ONS peaked at last day of RT (2.23), higher: mastectomy vs lumpectomy (2.66 vs 2.19) not different between race/ethnic groups. NHW women greater mean ONS score at 3 weeks into RT than other groups; however, NHW had lower mean ONS at 1 and 2 months post-RT (p < 0.01). ONS grade 4+ skin toxicities occurred: 15% of women at the end of RT, but no difference by race/ethnic cohorts. Conclusions: EASR peaks at end of RT with variation in time course by race/ethnicity. High grade toxicity uncommon and not different by race/ethnicity. This is first large study of RT EASR in a multi-racial/ethnic BC population. Additional analyses: RT dosimetry, genomics, DNA damage/repair biomarkers, and late effects are forthcoming. Clinical trial information: NCT01407770.
Pilot study of Scrambler therapy for the treatment of chemotherapy-induced peripheral neuropathy.
Authors: Deirdre R. Pachman, Breanna M. Linquist, Debra L. Barton, Kelliann C. Fee-Schroeder, Thomas J. Smith, Daniel Honore Lachance, Heshan Liu, Drew K. Seisler, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2012)

9075 Background: Chemotherapy-induced peripheral neuropathy (CIPN), a common dose-limiting side effect of chemotherapy, remains without known effective interventions. Preliminary data support that Scrambler therapy, a device which treats pain via non-invasive cutaneous electrostimulation, is beneficial for the treatment of CIPN. This pilot trial was performed to investigate the effect of Scrambler therapy for the treatment of CIPN. Methods: Eligible patients included those age ≥18 years, ECOG PS ≤2, life expectancy ≥3 months, with pain or CIPN symptoms of ≥1 month duration and tingling or pain ≥4/10 during the prior week. Patients were treated with Scrambler therapy to the affected area for up to 10 daily 30 minute sessions. Symptoms were monitored daily during therapy using a questionnaire to measure symptoms of neuropathy with a numerical analogue scale. Results: We report on the first 11 CIPN patients, enrolled between 7/18/2011 and 12/12/2011, 3 men and 8 women; mean age 57 years. Patients had history of exposure to various chemotherapeutic agents and the majority had symptoms &gt;2 years. The table portrays data at baseline, at the end of the 10 planned days of therapy, and the percent changes from baseline to the end of treatment, regarding patient reported pain, tingling, and numbness over the preceding 24 hours. There were no adverse events. Persistent benefit out to 5 weeks was seen in some patients; maturing data will be available by May 2012. Descriptive summary statistics formed the basis of data analysis. Further patients are being entered on this trial. Conclusions: Scrambler therapy appears to be beneficial in the treatment of CIPN. A prospective placebo-controlled clinical trial should be performed to confirm these preliminary findings. [Table: see text]
A retrospective review of clinical and pathologic aspects of inflammatory breast cancer: Clues for risk-adapted monitoring and therapy.
Authors: Joanna Rodriguez, Sheel Patel, R. Katherine Alpaugh, Juan Palazzo, Adam C. Berger, Tiffany P. Avery, Rebecca J. Jaslow, Pramila R. Anne, Nicole Lynn Simone, Theodore N. Tsangaris, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2014)

e11506 Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and is usually misdiagnosed or not recognized in clinical practice. Since the disease is relatively rare, is often included with other forms of non-IBC locally advanced cancers and there is a paucity of prospectively maintained databases that has limited detailed information on the peculiar epidemiological and clinical aspects of the disease. We sought to describe the clinical and pathologic characteristics of IBC using a large, prospectively maintained dataset of patients with IBC. Methods: Clinical and pathological characteristics were abstracted from the medical records of patients treated at two academic institutions in the US between 1999 and 2014. IBC was identified within medical records as T4d disease as defined by the sixth edition of the American Joint Committee on Cancer. We evaluated biomarkers status (ER, PR, HER-2), time and type of systemic and local therapy, recurrence time and site. Results: We identified one hundred and ninety eight patients with the diagnosis of Stage III/ IV IBC. Earliest time of diagnosis was 1999 with most recent diagnosis in 2013. Median age at presentation was less than 50 and 124 patients had disease subtype documented. The distribution of tumors was as follows: 40% patients had ER+/PR+/ HER 2 negative disease (luminal A), 19% ER+, PR+, HER2+ (luminal B); 31% were triple negative (TN), with only 11% of patients being ER-/PR-/HER2 positive (HER2). All patients received standard anthracycline and taxane based neoadjuvant regimen (HER-2 negative disease) or TCH or FEC/taxol herceptin (HER-2+ disease). The median follow up time was 40 months. The disease-free survival (DFS) was 16 months (range 2-48 months). Most common sites of recurrence were bone, loco-regional lymph nodes, and chest wall followed by lung/pleura, liver and brain. Conclusions: This retrospective study demonstrates that IBC patients are often younger and have a short DFS, which confirms the aggressive nature of this disease. The data suggest that IBC patients require close monitoring for disease recurrence and possibly additional systemic adjuvant interventions to improve survival.
Phase I/IB multicenter study of afatinib in combination with capecitabine in patients (pts) with refractory solid tumors and pancreatico-biliary cancers.
Authors: Amy E. Chang, Safi Shahda, William Proctor Harris, Stacey Cohen, Andrew L. Coveler, Bert H. O'Neil, Vijayakrishna K. Gadi, Reina Hibbert, Hannah H Lee, Anne Younger, Kinsey Ann McCormick, Colin Pritchard, Mary Weber Redman, E. Gabriela Chiorean
Journal: Journal of Clinical Oncology (2017)

TPS515 Background: The epidermal growth factor receptor (EGFR)/HER2 pathway is overactive in several solid tumors, including gastroesophageal, hepatic, colorectal, and pancreatico-biliary cancers. Afatinib is an irreversible inhibitor of the Erb family approved for metastatic non-small cell lung cancer with EGFR mutations. Afatinib downregulates thymidine synthase (TS) the intracellular target of fluoropyrimidine chemotherapy such as capecitabine. Treatment of colorectal cancer cell lines with cytotoxic drugs can up-regulate EGFR expression, and increase sensitivity to EGFR inhibition. Based on this preclinical rationale, and given that capecitabine is commonly used in refractory gastrointestinal cancers, we have developed a phase I/Ib trial to evaluate the safety and maximum tolerated dose (MTD) of afatinib with capecitabine in advanced solid tumors, and assess preliminary antitumor activity in pts with refractory pancreatico-biliary cancers at MTD. Methods: Eligible pts have metastatic solid tumors (phase I) or pancreatico-biliary cancers (phase Ib), ECOG PS 0-2 (PS 0-1 phase Ib), any number of prior therapies (phase I), or ≤ 2 prior therapies (phase Ib), no prior erlotinib (phase Ib), and have archived paraffin embedded tumor tissue, or ability to undergo tumor biopsy at baseline. Tumor tissue is analyzed with UW-OncoPlex, a multiplexed gene sequencing panel of 200+ cancer-related genes, to identify predictive biomarkers of benefit. The study design is standard “3+3”. Afatinib is administered orally (PO) daily (QD) in escalating doses of 20, 30 and 40 mg, with capecitabine at 1000 mg/m 2 PO BID Days 1-14, in 21-day cycles (C). Dose limiting toxicity (DLT) is assessed in C1. Once the MTD is identified, the phase Ib expansion cohorts will enroll 15 pts each with refractory pancreatic and biliary cancers, with afatinib dosed at MTD and standard dose capecitabine. The study was activated in November 2015, and to date 4 pts were enrolled in cohort 1, 3 pts in cohort 2, and 2 pts in cohort 3. The phase I is ongoing and the phase Ib is expected to start enrollment in December 2016. Clinical trial information: NCT02451553.
Results of the dose-escalation portion of a phase 1/2 study (CHAMPION-1) investigating weekly carfilzomib in combination with dexamethasone for patients with relapsed or refractory multiple myeloma.
Authors: James R. Berenson, Leonard M. Klein, Robert M. Rifkin, Priti Patel, Sandra Dixon, Ying Ou, Alan Cartmell
Journal: Journal of Clinical Oncology (2014)

8594^ Background: Carfilzomib (CFZ) is a selective proteasome inhibitor approved in the US for the treatment of relapsed and refractory multiple myeloma (MM). This multicenter, single-arm phase 1/2 study (NCT01677858) is evaluating the safety and efficacy of once-weekly CFZ with dexamethasone (DEX). Methods: Patients (pts) with relapsed or refractory MM who received 1−3 prior regimens were eligible. Pts received CFZ as a 30-minute IV infusion on days (D) 1, 8, and 15 of a 28-day cycle in a standard 3+3 dose-escalation scheme. All pts received CFZ at 20 mg/m2 on D1 of cycle 1; subsequent doses started at 45 mg/m2 and were escalated to 56, 70, or 88 mg/m2in successive cohorts until the maximum tolerated dose (MTD) was reached. Pts received 40 mg DEX (IV or oral) on D1, 8, 15, and 22 of cycles 1–8; DEX was omitted on D22 in cycles ≥9. Response was assessed by IMWG criteria; minimal response (MR) was assessed by EBMT criteria. The primary objective of the phase 1 portion of the study was to determine the MTD. Results: As of 11/5/2013, 27 pts were enrolled (median age, 64 years [range, 43–84]; median prior regimens, 1 [range, 1–3]). At 88 mg/m2, 2 dose-limiting toxicities (DLTs) were observed: grade [Gr] 3 dyspnea and Gr 3 vomiting. At the MTD (70 mg/m2), 1 patient of 15 experienced a DLT (Gr 3 dyspnea). Gr ≥3 AEs reported in >1 pt were thrombocytopenia, increased blood creatinine, dyspnea, and hyperglycemia (n=2 each; all Gr 3). No Gr ≥3 peripheral neuropathy was reported. All 27 pts were included in the preliminary efficacy evaluation. The overall response rate (ORR; ≥partial response) was 63% and the clinical benefit rate (CBR; ≥MR) was 74%. At the MTD, the ORR was 60% and the CBR was 67%. Pharmacokinetic analysis (n=21) showed a dose-dependent increase in mean Cmax and AUC for 20–88 mg/m2CFZ. The mean terminal half-life was ~0.8 hours. Conclusions: At the MTD, weekly CFZ with DEX had an acceptable safety and tolerability profile with promising efficacy after a short follow-up period in pts with relapsed or refractory MM. The phase 2 portion of the study is currently enrolling pts at 70 mg/m2 CFZ. Updated results from the phase 1/2 study will be presented. Clinical trial information: NCT01677858.
Anti-tumor activity of partially HLA-matched irradiated blood mononuclear cells in patients with advanced malignancies
Authors: R. Strair, M. Gharibo, K. Taber BS, M. Kuriyan, R. Dipaola, M. Stein, M. Todd, A. Rubin, E. Lattime, D. Medina
Journal: Journal of Clinical Oncology (2006)

2552 Background: We previously demonstrated the safety and efficacy of HLA-haploidentical blood mononuclear cells (MNCs) administered in the absence of preparative therapy to patients with metastatic renal cell carcinoma (RCC) (J Clin Oncol 21:3785–91.2003). The efficacy of this therapy is evaluated further in patients with advanced malignancies. Methods: Patients with advanced malignancies who had HLA- haploidentical donors were enrolled. Donors underwent 12–15 L leukapheresis. MNCs were processed by irradiation (25 Gy) and immediately infused. Disease evaluation was undertaken every 8 weeks. Repeat infusions were given every 8 weeks until disease progression. Results: 30 patients with diverse diagnoses, including 9 patients with a hematological malignancy were treated. Three of 13 patients with RCC had disease response, and 1 of 2 patients with melanoma had a mixed response. A patient with imatinib mesylate-refractory chronic myelogenous leukemia (CML) had a transient response. A patient with refractory acute myelogenous leukemia (AML) had disease response in conjunction with therapy. Treatment was associated with minimal toxicity and radiographic responses in patients with RCC did not occur until after 2–3 treatments. Host CD8+ cells reactive with the Pr-1 peptide of proteinase 3 were induced in association with disease response in a patient with AML. Additional studies identifying disease targets and mechanisms by which infusion of irradiated HLA-haploidentical cells are associated with disease response are ongoing. Conclusions: Disease response is seen with irradiated allogeneic MNCs administered outside the context of hematopoietic stem-cell transplantation. Evidence for anti-tumor activity is seen in isolated patients with RCC, melanoma, CML and AML. The temporal nature of the response in RCC in combination with the very limited survival of the infused cells raises the possibility of induction of a host-mediated anti-tumor effect. This hypothesis is supported by induction of host CD8+ T cells reactive with a tumor-associated peptide in a patient with AML. Given the lack of toxicity, broad availability of related haploidentical donors and the relative low financial cost, this form of cellular therapy should be developed further. No significant financial relationships to disclose.
Nintedanib (N) plus best supportive care (BSC) versus placebo plus BSC for the treatment of patients (pts) with metastatic colorectal cancer (mCRC) refractory to standard therapies: Health-related quality of life (HRQoL) results of the Phase III LUME-Colon 1 study.
Authors: Heinz-Josef Lenz, Josep Tabernero, Takayuki Yoshino, Sara Lonardi, Alfredo Falcone, María Luisa Limón Mirón, Mark P. Saunders, Alberto F. Sobrero, Young Suk Park, Reyes Ferreiro Monteagudo, Yong Sang Hong, Jiri Tomasek, Hiroya Taniguchi, Fortunato Ciardiello, Mouna Sassi, Barbara Peil, Claudia Hastedt, Matus Studeny, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2017)

671 Background: N is a multiple angiokinase inhibitor (including VEGFR, PDGFR and FGFR). A randomised Phase III study, LUME-Colon 1 (NCT02149108), evaluated the efficacy and safety of N in pts with refractory mCRC after failure of standard therapies. LUME-Colon 1 showed a statistically significant improvement in PFS (HR [95% CI] 0.58 [0.49–0.69]; p &lt; 0.0001) but no difference in OS (HR [95% CI]: 1.01 [0.86–1.19]; p = 0.8659). Here, we report the HRQoL outcomes. Methods: 768 pts with mCRC adenocarcinoma refractory to standard chemotherapy were randomised 1:1 to receive either N (200 mg bid) + BSC or P (bid) + BSC in 21-day courses until disease progression or undue toxicity. HRQoL was assessed every 21 days using the EORTC QLQ-C30 instrument; the main endpoints of interest were the differences in mean scores up to median follow-up time (treatment difference, TD) for physical functioning (PF) and global health status/QoL (QL) scales using a longitudinal model, with 95% CIs and associated p-values adjusted for baseline stratification factors. Time to deterioration (TTD) of scores and status change ( ≥ 10 point change from baseline) were also assessed. Results: Compliance with questionnaire completion was high ( &gt; 85% in first 12 cycles). Mean baseline (N vs P) PF (80 vs 80) and QL (65 vs 65) scale scores were balanced between treatment arms. The mean TD favoured N vs P for PF scale scores (TD 2.66 [95% CI: 0.97–4.34]; p = 0.0020) and QL scale scores (TD 1.61 [95% CI: −0.04–3.27]; p = 0.0555). TTD of PF (HR 0.84; 95% CI: 0.69–1.03; p = 0.0904) and QL (HR 0.90; 95% CI: 0.75–1.08; p = 0.2674) scores were not significantly different between treatment groups, although the percentage of patients with improved PF (17.2% vs 11.8%; p = 0.0462) and QL scores (30.3% vs 21.6%: p = 0.0102) were both significantly higher for N vs P. Conclusions: In LUME-Colon 1, patient reported outcomes confirmed that overall HRQoL was not impaired by treatment with N. There was evidence for improvement of PF and QL with N vs P, corresponding to the significant increase in PFS observed. Clinical trial information: NCT02149108.
Association of time from definitive therapy (DT) to start of androgen deprivation therapy (ADT) for metastatic disease and survival outcomes in men with new metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: David Michael Gill, David D. Stenehjem, Heather H. Cheng, Elizabeth Riley Kessler, Andrew W. Hahn, Sumati Gupta, Anitha Alex, Shiven B. Patel, Namita Chittoria, Przemyslaw Twardowski, Ulka N. Vaishampayan, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2017)

265 Background: Few objective criteria are considered for risk stratification for treatment decision making in men with new mHSPC. Time between DT for localized disease, and start of ADT for new mHSPC may predict response to ADT, and prognosticate outcomes in this setting. Methods: In this multicenter study, men with newly diagnosed mHSPC with prior history of definite therapy for localized prostate cancer were included. Kaplan-Meier and Cox proportional hazard methods assessed time to castration resistance (CRPC) and overall survival (OS) from initiation of ADT, and correlated with the time elapsed from DT to initiation of ADT for new mHSPC. Results: A total of 112 men with new mHSPC initiating ADT, with prior definitive therapy were eligible (all median: age 68 yrs, Gleason score 7, PSA 14 ng/ml, ECOG 0, median time from DT to start of ADT for new mHSPC 54 months). In the univariate analysis, time from DT to start of ADT of &lt; 60 months vs ≥ 60 months significantly correlated with duration of response to ADT and outcomes (Table). After adjustment for Gleason score and log PSA, time from DT to start of ADT for new mHSPC (&lt;60 vs ≥60 months) remained an independent and a significant predictor of time to CRPC (HR 1.92 95% CI 1.02-3.90, p=0.044), and showed trends towards predicting OS (HR 1.77 95% CI 0.60-6.19, p=0.33). Conclusions: Time from DT for localized prostate cancer to initiation of ADT for new mHSPC independently predicts response to ADT, and may aid in risk stratification for treatment decision making in men with new mHSPC. These hypothesis-generating data require validation in a larger cohort. [Table: see text]
IDH1 status and survival benefit from surgical resection of enhancing and nonenhancing tumor in malignant astrocytomas.
Authors: Daniel P. Cahill, Jason Beiko, Dima Suki, Sujit S. Prabhu, Jeffrey Weinberg, Frederick F. Lang, Mark R. Gilbert, Ganesh Rao, Ian E. McCutcheon, Kenneth D. Aldape, Raymond Sawaya
Journal: Journal of Clinical Oncology (2012)

2019 Background: The value of maximal safe resection for malignant astrocytic gliomas (AA, WHO Grade III anaplastic astrocytoma and GBM, WHO Grade IV glioblastoma) has sometimes been controversial, because of confounding between measures of surgical resection and other prognostic factors. IDH1 gene mutations are associated with improved survival in glioma patients, and are thought to identify tumors with a distinct molecular evolutionary origin. We sought to determine the prognostic impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomas. Methods: Clinical parameters including preoperative and postoperative MRI-based tumor volume were recorded prospectively on 407 malignant astrocytoma patients – AA (n=157) and GBM (n=250). IDH1 status was assessed by sequencing and R132H-specific immunohistochemistry. Results: The measures of surgical resection associated with longer survival differed between IDH1 wild-type and mutant tumors. In multivariate analyses of IDH1 wild-type tumors (controlling for age, Karnofsky performance score, tumor location, and tumor grade), residual postoperative enhancement was associated with a median survival of 9.9 mo vs. 17.4 mo with no enhancement (HR=1.73, 95% CI, 1.19-2.52, p=.004). Residual non-enhancing disease, however, was not associated with survival (scored as continuous volumetric cc, 95% CI 0.99-1.01, p=.608). These results are consistent with prior studies of GBM, which are largely IDH1 wild-type lesions (Lacroix et al., J Neurosurg 95:190-8, 2001). In contrast, in IDH1 mutant tumors, both residual enhancing (HR=7.93, 95%CI 1.14-55.22, p=.037) and non-enhancing (HR=1.03, 95% CI 1.01-1.05, p=.005) postoperative tumor burden were associated with worse survival. Conclusions: These data suggest surgical resection in malignant astrocytic gliomas may be individualized based on IDH1 genotype. IDH1 mutant tumors have a better baseline overall prognosis, therefore more aggressive surgery and tolerance of temporary peri-operative neurologic deficits can be weighed in an attempt to gain the additional survival benefit that appears to be associated with reducing non-enhancing tumor burden.