tbuckley/cabot-search huggingface dataset:
Updated results of the SOFT study: A randomized phase III trial of S-1/oxaliplatin (SOX) plus bevacizumab versus 5-FU/<i>l</i>-LV/oxaliplatin (mFOLFOX6) plus bevacizumab in patients with metastatic colorectal cancer (mCRC).
Authors: Masato Nakamura, Yasuhide Yamada, Daisuke Takahari, Hiroshi Matsumoto, Hideo Baba, Kazuhiro Yoshida, Motoki Yoshida, Shigeyoshi Iwamoto, Ken Shimada, Yoshito Komatsu, Yasutsuna Sasaki, Taroh Satoh, Keiichi Takahashi, Hideyuki Mishima, Kei Muro, Masahiko Watanabe, Yuh Sakata, Satoshi Morita, Yasuhiro Shimada, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2014)

3586 Background: As previously reported (Yamada Y, et al. Lancet Oncol. 2013 Dec;14(13):1278-86), the SOFT study demonstrated that SOX plus bevacizumab (SOX+Bev) was non-inferior to mFOLFOX6 plus bevacizumab (mFOLFOX6+Bev) in terms of the primary endpoint of progression-free survival (PFS). We now report the final overall survival (OS) after a median follow-up of more than 3 years. Methods: The SOFT study was an open-label, non-inferiority, randomized phase III trial. Chemotherapy-naïve patients with mCRC, an ECOG PS of 0-1, and adequate organ functions were randomized to receive either mFOLFOX6+Bev (5 mg/kg of bevacizumab, followed by 200 mg/m2 of l-leucovorin given simultaneously with 85 mg/m2 of oxaliplatin, followed by a 400 mg/m2 bolus of 5-FU on day 1 and then 2,400 mg/m2 of 5-FU as an intravenous infusion over the course of 46 h, every 2 weeks) or SOX+Bev (7.5 mg/kg of bevacizumab, 130 mg/m2 of oxaliplatin on day 1, and 40−60 mg of S-1 twice daily for 2 weeks, followed by a 1-week rest). The primary endpoint was PFS. Patients’ data were finally updated in September 2013. Results: At this final analysis, the median survival time(MST) was 29.7 months (95% CI: 26.5−33.1) with mFOLFOX6+Bev and 29.6 months (95% CI: 25.8−34.7) with SOX+Bev (median follow-up, 37.7 months). The HR for OS was 1.018 (95% CI: 0.823−1.258). Median PFS was 11.7 months (95% CI: 10.9−13.3) with mFOLFOX6+Bev and 12.2 months (95% CI: 10.7−13.0) with SOX+Bev. The HR for PFS was 1.051 (95% CI: 0.876−1.262), and the p value for non-inferiority was 0.0115 (median follow-up, 31.2 months). In the subgroup analysis of PFS and OS, we recorded no clinically significant interactions between the assigned regimen and any factors. The safety profile was almost similar to primary analysis results. Conclusions: In this study, the MST was at least 29.5 months in both groups, indicating similar OS. Our results reconfirmed that SOX+Bev is non-inferior to mFOLFOX6+Bev in terms of PFS as first-line treatment for mCRC. SOX+Bev can thus be used instead of mFOLFOX6+Bev. Clinical trial information: JapicCTI-090699.
Effect of enzalutamide on sensitivity in prostate cancer cells to radiation by inhibition of DNA double strand break repair.
Authors: Maryam Ghashghaei, Thierry Muanza, Miltiadis Paliouras, Tamim Niazi
Journal: Journal of Clinical Oncology (2017)

208 Background: Prostate cancer is the second leading cause of cancer-related deaths amongst men in North America. Data suggests that, following radiation therapy (XRT), androgen receptor (AR) enhances DNA damage repair and contributes to resistance of prostate cancer (PCa) cells to XRT. At present AR-pathway inhibition is the mainstay treatment of metastatic castration resistance prostate cancer (mCRPC). Enzalutamide (ENZA), a potent AR inhibitor is one of the approved drugs in this setting. The purpose of this study was to assess the potential radiosensitization of ENZA and its mechanism of action in hormone resistant PCa cells. Methods: The effect of ENZA alone or in combination with XRT was assessed on hormone-sensitive, (HS: LNCaP, PC3-T877A) and insensitive PCa cells (HI: PC3, PC3-AR V7, C4-2) using viability and clonogenic assays, cell cycle arrest and DNA damage analysis. Results: MTT assay demonstrates that ENZA significantly inhibits the proliferation of HS PCa cells in a dose dependent manner whereas CRPC required ENZA in combination with ADT (androgen deprivation therapy). Additionally, clonogenic assay proves that concurrent administration of ENZA or ADT+ENZA and XRT led to a supra-additive antitumor effect with the dose enhancement factor of 1.76±0.008 in LNCaP, 1.65±0.01 in PC3-T877A and 1.35±0.003 in C4-2 respectively at surviving fraction of 0.1. This effect was not observed in PC3 and PC3-AR V7 cells pre-treated with ENZA (in all cases DEF = 1 at SF = 0.1). Additionally, the level of γH2AX increased in HS cells and CRPC cells treated with ENZA/ADT+ENZA and XRT when compared to XRT alone. The enhanced H2AX activity remained unchanged up to 24 hours after combination treatment. Furthermore, there is an initial inhibition of DNA-PKcs in HS and CRPC cells treated with ENZA/ADT+ENZA administered before XRT. Conclusions: Our data suggest that the higher efficacy of ENZA/ENZA+ADT and XRT could be partially due to inhibition of DNA damage repair. Our results demonstrated a significant enhancement of XRT efficacy and confirms the rational for the ongoing combination clinical trials with XRT.
Is sarcopenia a useful prognostic indicator in patients with squamous cell carcinoma of the penis?
Authors: Michelle Christodoulidou, Sorrel Burden, Debra Gibson, Charalampos Attipa, Navin Ramachandran, Raj Nigam, Peter Malone, Anita Mitra, Simon Lal, Toby Richards, Asif Muneer
Journal: Journal of Clinical Oncology (2017)

426 Background: Sarcopenia is a decrease in skeletal muscle mass and is a quantifiable marker of frailty associated with poor oncological outcomes. Currently there are no studies using sarcopenia as a prognostic indicator for patients with penile cancer. This study investigated the association of sarcopenia with mortality and morbidity outcomes in penile cancer patients in a specialist centre. Methods: A retrospective case-controlled study was performed. Patient cohort comprised 50 patients with metastatic penile cancer ( &gt; pN2 disease) and 50 patients with non-metastatic disease (N0) ; minimum follow-up period of 2 years. Sarcopenia was classified as a skeletal muscle index &lt; 55cm 2 /m 2 and was measured using software and CT imaging. Results: Sarcopenia was present in 31% of our cohort (n = 100). A univariate analysis showed a statistically significant association between the following parameters and patient mortality; sarcopenia (p = 0.005), metastatic disease (p = 0.001), tumour stage (p = 0.001), sarcomatoid squamous cell carcinoma (p = 0.009), CIS (p = 0.034), lymphovascular invasion (LVI) (p = 0.001) and perineural invasion (p = 0.002). Logistic regression analysis found an association between mortality and sarcopenia (p = 0.035) and metastatic disease (p = 0.000) and approached statistical significance with LVI (p = 0.061). Subdividing our cohort into metastatic and non-metastatic groups, showed that sarcopenia was associated with mortality in patients with metastatic disease but was not associated with post-operative complications or chemo-radiotherapy toxicity. Interestingly, sarcopenia was associated with post-operative infection in patients undergoing surgery for non-metastatic disease (p = 0.027). Additionally, for every day remaining in hospital after the 4 th post-operative day, there was a 1.275 increase in the risk of death in patients with sarcopenia. Conclusions: Sarcopenia has a potential role as a novel prognostic indicator and could be used as a risk stratification tool in patients with metastatic penile cancer when deciding treatment options. By identifying this subgroup, additional nutritional support and a supervised exercise program can be implemented to improve the morbidity rate.
A phase Ib/II study evaluating the efficacy of doxorubicin (D) with or without a human anti-PDGFRα monoclonal antibody olaratumab (IMC-3G3) in the treatment of advanced soft tissue sarcoma (STS).
Authors: William D. Tap, Brian Andrew Van Tine, Anthony D. Elias, Michael B. Livingston, Mark Agulnik, Matthew M. Cooney, Bartosz Chmielowski, Andrew Jacob Brenner, Gregory K. Pennock, Neeta Somaiah, Long H. Dang, Gary G. Tian, Robin Lewis Jones, Scott H. Okuno, Nick Loizos, Johannes Nippgen, Gary K. Schwartz
Journal: Journal of Clinical Oncology (2012)

TPS10099 Background: PDGFRα is a receptor commonly overexpressed in STS. Olaratumab is a fully human IgG1 MAb which specifically binds to human PDGFRα and blocks PDGFR-mediated signaling pathways. Olaratumab demonstrated significant tumor inhibition as a monotherapy and in combination with standard chemotherapy in preclinical human sarcoma xenograft models. A Phase 1b/2 clinical trial for patients with advanced or metastatic STS is currently enrolling patients in 9 sites across the United States; approximately 45 patients have been randomized. Methods: In Phase 1b, patients received olaratumab (15 mg/kg) via intravenous infusion on Days 1 and 8 of each 21-day cycle and D (75 mg/m²) 1 hour after olaratumab on Day 1. Phase 1b was completed without encountering dose-limiting toxicities; enrollment into Phase 2 has begun. The primary endpoint of the Phase 2 portion is to compare progression-free survival in patients with advanced STS when treated with D plus olaratumab versus D alone. Planned enrollment goal for Phase 2 is 130 patients. Patients are required to be ≥ 18 years old with ECOG 0-2, have appropriate organ function and histologically confirmed, measurable, and advanced STS. There is no restriction on the number of prior therapies. Patients are randomized 1:1 to either D plus olaratumab (Arm A) at same dose/schedule as in Phase 1b or D alone (Arm B). All patients can receive dexrazoxane. Upon completion of 8 cycles, patients in Arm A continue with olaratumab monotherapy. Patients in Arm B who develop disease progression during or after treatment can subsequently receive olaratumab monotherapy. Patients are stratified to treatment arms according to PDGFRα expression (positive vs. negative), number of previous lines of treatment, sarcoma subtype, and ECOG performance status. Response assessment occurs every 6 weeks. Exploratory analyses include biomarkers of olaratumab pharmacodynamic activity including PDGF ligands, PDGFR downstream molecules, VEGF, and changes in vascularity of tumor specimens.
Understanding differences in the receipt of chemotherapy between African-American (AA) and white (W) patients with stage III colon cancer
Authors: B. N. Polite, B. Huskey, M. McKee, J. J. Dignam
Journal: Journal of Clinical Oncology (2007)

6568 Background: Even when stage is controlled for, AA are more likely to die from colon cancer than are W. Previous research suggests that AA are less likely to receive adjuvant chemotherapy for Stage III colon cancer than W. This study examines the differences in the receipt of chemotherapy for stage III colon cancer and the reasons behind those differences. Methods: The records of patients diagnosed with and/or receiving their first-course of treatment for Stage III colon cancer at the University of Chicago between 1995–2004 were examined. Specifically, patient charts were audited to determine whether the patients had received chemotherapy, and if not, the documented reasons for the non-receipt of therapy. In the case of incomplete records, the patients’ outside physicians were contacted to ascertain the chemotherapy history. Chemotherapy information was unavailable for only 13 patients (5 AA and 8 W). Results: A total of 186 patients (110 AA and 76 W) were diagnosed with stage III colon cancer at the University of Chicago between 1995–2004. No significant differences were seen with respect to age, sex or tumor location between AA and W. In total, 65% of AA versus 82% of W received chemotherapy (OR 0.43; 95% CI: 0.20–0.86). AA were more likely to not undergo chemotherapy because of comorbidities (OR 3.80; 95%CI 1.35–10.50). Those pts not receiving therapy because of comorbidities had a poorer overall survival than those who received therapy (HR 5.9; 95%CI 3.4–10.3). This effect held for both AA and W pts (p=0.65 for race and comorbidity interaction). Among the 146 pts (86AA, 63W) for whom it is known that chemotherapy was recommended, AA were over 9 times as likely to have a documented refusal (OR 9.5; 95% CI 1.19–75.4). These findings were robust to adjustments for age, sex, insurance status and marital status. Conclusions: AA were significantly less likely than W to receive chemotherapy for stage III colon cancer. The reasons for the difference include both refusal of therapy and the presence of comorbidities that the treating physicians felt were a contraindication to therapy. Future research should be directed at better understanding the reasons behind the higher refusal rates for AA patients. No significant financial relationships to disclose.
Efficacy and side-effect profile of long-term bisphosphonate therapy in patients (pts) with multiple myeloma (MM): MRC myeloma IX study results.
Authors: Gareth J Morgan, Graham H. Jackson, Faith Davies, Ping Wu, Walter Gregory, Sue E Bell, Alexander Szubert, Nuria Navarro Coy, Mark Drayson, Roger G. Owen, Sylvia Feyler, John Ashcroft, Fiona Ross, Jennifer Byrne, Huw Roddie, Claudius Rudin, Kevin Boyd, Gordon Cook, J. Anthony Child
Journal: Journal of Clinical Oncology (2012)

8015 Background: Bisphosphonates (BPs) are recommended in pts with osteolytic lesions from MM. However, data on the long-term efficacy and safety of BPs beyond 2 y is somewhat limited. The MRC Myeloma IX study has already revealed significant overall survival (OS) and progression-free survival (PFS) benefits for zoledronic acid (ZOL) over clodronate (CLO) in MM pts (N = 1960) initiating chemotherapy (Morgan GJ, et al. Lancet. 2010). We now report the efficacy and safety of BP therapy with long-term follow-up. Methods: Newly diagnosed MM pts were randomized to ZOL (4 mg IV q 21-28 days) or CLO (1600 mg/day PO) plus antimyeloma therapy. BPs continued at least until disease progression. PFS and OS were estimated using Kaplan-Meier methodology. Hazard ratios (HRs) were calculated using stratified Cox models. Adverse events (AEs) were monitored continuously and analyzed using cumulative incidence functions. Results: At a median follow-up of 5.8 y in 1960 evaluable pts, ZOL improved PFS (HR = 0.88; P = .01) and OS (HR = 0.88; P = .03) vs CLO. Both BPs were generally well tolerated, and acute renal failure events were similar between groups (ZOL 5.2% vs CLO 5.8% at 2 y, with incidence plateaued thereafter). Overall incidence of confirmed osteonecrosis of the jaw (ONJ) has remained low (ZOL 3.7% vs CLO 0.5%; P &lt; .0001). ONJ incidence was lower among pts receiving thalidomide-containing regimens (1.4%) vs no thalidomide (2.76%; P = .041). Events were generally low-grade, most occurred between 8 and 30 mo (median time to ONJ = 23.7 mo), and cumulative incidence plateaued at ~36 mo. Ten pts had data on ONJ recovery: complete recovery in 4 pts, improvement in 2 pts, no change in 3 pts in the ZOL group; and no change in 1 CLO pt. Dental surgery or trauma preceded ONJ in 6 ZOL pts. Conclusions: ZOL provided sustained PFS and OS improvements vs CLO during long-term therapy in the MRC Myeloma IX study. Overall incidence of AEs was similar between groups, with no notable changes during long-term therapy. ONJ incidence remained low during long-term (&gt; 2.5 y) therapy and was reduced in pts receiving thalidomide (possibly because of anticytokine effects of this agent).
Characteristics of HIV+ lung cancer cases in a large clinical population: Implications for lung cancer screening.
Authors: Marina Shcherba, H. Dean Hosgood, Juan Lin, David Hanna, Uriel R. Felsen, Mindy Ginsberg, Linda Fisher, Kevin Wilson, Julie Chung, Xiaonan Xue, Kathryn Anastos, Bilal Piperdi, Simon Spivack, Steven M. Keller, Howard D. Strickler, Missak Haigentz
Journal: Journal of Clinical Oncology (2014)

1569 Background: Lung cancer (LCa) accounts for ~30% of cancer deaths and 10% of non-HIV-related deaths among HIV(+)s. Compared to those in the general population, even after accounting for smoking, HIV(+)s have a 2.5–5-fold higher risk of LCa, and are diagnosed younger. The National Lung Screening Trial (NLST) demonstrated survival improvements with low dose CT (LD-CT) screening in persons at high lung cancer risk (age 55-74 with ≥30 pack-years [pys] of smoking). We examined the age and smoking histories of HIV+ LCa patients to determine who would have met NLST screening eligibility. Methods: The Cancer Registry (42,967 cancer cases) and the HIV Integrated Clinical Database (14,927 HIV+s) at Montefiore Medical Center – Einstein (Bronx, NY) were linked to identify HIV+ cancer cases between 2000-2012. Chart review was performed for those with LCa. Results: Of the 935 invasive cancers in HIV+s, 90 (9.6%) were LCa (62% men, 38% women). Histology was 11% small cell, 20% squamous and 37% adenocarcinoma, 2% large cell, and remaining 30% were classified as non-small cell carcinomas. Median age at LCa diagnosis was 54 years ([y]; range: 24–72), with 2% <35y, 52% 35-54y, 46% ≥55y. 4% were never smokers, and 3% had <15pys, 24% 15-29pys, 68% ≥30pys. Overall, 66 cases (73%) did not meet NLST age or smoking criteria. Most cases (85%) had been followed for HIV care. The median CD4+ was 238 cells/μL, and median HIV viral load was 81 copies/mL. LCa was stage I in 8%, stage II in 11%, stage III in 23%, and stage IV in 58%. All stage I/II cases underwent surgical resection. Conclusions: Most HIV+ LCa cases failed to meet NLST criteria for LD-CT screening due to age <55y or pys <30. If LD-CT is to be utilized in this high-risk population, age and smoking thresholds may need to be lowered. Notably, 19% of tumors were diagnosed at stage I/II without routine screening, reinforcing the potential to identify LCa at a treatable stage in HIV(+) persons.
Frequency and risk factors of potential drug interactions in breast cancer patients.
Authors: Fatma Acar, İbrahim Hakkı Dursun, Hakan Harputluoglu, Ali Yiğit, Mehmet Salih Kilic, Emin Tamer Elkiran
Journal: Journal of Clinical Oncology (2014)

e17669 Background: Breast cancer is the most common cancer in women. Breast cancer is seen in one of every six women during their lifetime period. In addition to cytotoxic treatment, these patients use various medication for hormonal treatment, treatment of comorbid diseases and palliative treatment. In our study we aimed to evaluate frequency, severity, clinical importance and risk factors of drug interactions in breast cancer patients. Methods: 200 breast cancer patients who applied to Inönü University Medical Faculty Turgut Özal Hospital’s medical oncology inpatient and outpatient clinics are included to this study. Patient’s demogrofical features, their treatment regimen, comorbid diseases and other medication being used in purpose of supportive treatment are gathered with a questionnaire. The web-based
Antiemetic prescribing practices using a computerized physician order entry system.
Authors: Kunal C. Kadakia, Alexis D. Leal, Drew K. Seisler, Rui Qin, Kelliann C. Fee-Schroeder, Darryl Grendahl, Kristine Sorgatz, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2013)

e17538 Background: Adherence to guideline-consistent chemotherapy-induced nausea and vomiting (CINV) prophylaxis is suboptimal. The primary aim of this study was to evaluate the magnitude of compliance to institutional guideline-directed antiemetic prophylaxis using a computerized physician order entry system at a single tertiary care institution. A nurse survey was also performed to evaluate how oncology practices, within a cooperative group, manage clinician orders for the prevention of CINV. Methods: The electronic medical records of 100 consecutive patients were evaluated. The primary endpoint was the incidence of compliance to provide all aspects of institutional guideline-directed antiemetic prophylaxis for acute (Day 1) and delayed (Days 2-4) CINV for patients receiving high, moderate, low, and minimally-emetogenic chemotherapy (HEC/MEC/LEC/MinEC). Noncompliance was declared if a recommended antiemetic was not prescribed per the guidelines or if additional antiemetics were prescribed. Descriptive analyses were performed on the convenience sample. Logistic regression was applied to determine the association of potential factors with noncompliance. Results: The incidence of compliance on Days 1-4 was 94%. Half of the noncompliant events occurred on Day 1 alone and involved the omission of pre-chemotherapy prochlorperazine in patients receiving LEC (3 of 6, 50%). There was a high-degree of compliance to institutional guidelines for delayed CINV (97%). Patients receiving doxorubicin/cyclophosphamide were numerically less likely to receive institutional guideline-directed antiemetic prophylaxis, compared to patients receiving other chemotherapy regimens (OR: 0.24 (0.04, 1.36), p-value: 0.05). No other factors were significantly predictive for compliance. The nurse survey demonstrated significant variability amongst the involved institutions, with regards to antiemetic prescribing practices. Conclusions: Computerized physician order entry is associated with impressive adherence to clinician prescribing practices, according to institutional guideline-directed antiemetic prophylaxis, for preventing acute and delayed CINV.
Is online patient information at NCI cancer centers too complex for broad general readership?
Authors: Stephen Rosenberg, Dave Francis, Craig Hullett, Zachary Scott Morris, Jeffrey Brower, Michael Fisher, Bethany Marie Anderson, Michael F. Bassetti, Randall J. Kimple
Journal: Journal of Clinical Oncology (2015)

6526 Background: The NIH and the Department of Health and Human Services recommend that online patient information (OPI) be written at a 6th grade level to facilitate broad readership comprehension. We sought to assess the readability of OPI found on NCI Designated Cancer Center websites across the US. Methods: Cancer.gov was utilized to identify 68 NCI Designated Cancer Center websites from which we collected both general OPI and specific OPI on breast, prostate, lung, and colon cancer. We then performed a readability analysis with 10 commonly used readability tests: the New Dale–Chall Test, Flesh Reading Ease Score, Flesh-Kinkaid Grade Level, FORCAST test, Fry Score, Simple Measure of Gobbledygook, Gunning Frequency of Gobbledygook, New Fog Count, Raygor Readability Estimate, and Coleman-Liau Index. We sought to test the hypothesis that the readability of OPI from NCI Designated Cancer Centers would be written at the 6thgrade level. As a secondary analysis, we compared readability of OPI between comprehensive and non-comprehensive cancer centers, by geographic region, and to the OPI produced by the American Cancer Society (ACS). Results: Data from 40 comprehensive and 18 non-comprehensive NCI Designated Cancer Centers were available for analysis (7 non-clinical centers and 3 without appropriate OPI were excluded). A mean of 30,507 words (range 5,732 – 147,425) were analyzed. A composite measure of grade level was constructed using the 8 readability measures that provide a grade level. These measures were strongly correlated and formed a reliable measure (SI alpha = 0.98). The mean grade level of 12.46 (95% CI: 12.13 – 12.79) was significantly greater than the target reading level (t (57) = 38.15, p < .001). No statistically significant difference in readability was seen when comparing comprehensive vs. non-comprehensive centers (t range 0.42 – 1.19, p = 0.24 – 0.69). Regional differences were identified in 4 of the 10 readability metrics (p < .05). The ACS OPI provides easier language, 7-9th grade level, across all tests (p< .01). Conclusions: OPI found on NCI Designated Cancer websites is more complex for the readership than recommended. This may limit the reach and impact of important cancer information to the public.