bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and predictors of posttraumatic stress disorder in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study
Authors: Stuber M. , Meeske K. , Zebrack B. , Krull K. , Stratton K. , Leisenring W. , Robison L. , Zeltzer L. 
Published: February 2017

CRA10002 Background: This study examined prevalence and demographic- and disease-related correlates of posttraumatic stress disorder (PTSD) among 6,542 adult childhood cancer survivors and 368 siblings from the Childhood Cancer Survivor Study. Methods: Subjects were dichotomized based on full PTSD criteria, using the Foa PTSD self-report measure to assess posttraumatic stress symptoms of intrusion of unwanted memories, avoidance of event reminders, and increased startle response, and the Brief Symptom Inventory-18 and the SF-36 subscale, role limitation due to emotional health, to evaluate clinical distress or impaired function. A self-report questionnaire provided demographic information and medical abstraction provided cancer reatment data. Multivariable generalized linear models were used to compare prevalence of PTSD among cancer survivors to siblings and to examine relationships between PTSD and demographic and disease-related factors. Relative risks (RR) were calculated based on a Poisson distribution with robust error variances. Results: Five hundred eighty-nine (9%) childhood cancer survivors and 8 (2%) siblings met criteria for a diagnosis of PTSD (RR = 3.83, 95% CI 1.96–7.48, p < 0.0001). Among cancer survivors, there was significantly more PTSD reported by women from minority backgrounds (p < 0.05). Other demographic factors associated with PTSD were having less than a college education (p < 0.05), being unmarried (p < 0.001), having an annual income less than $20,000 (p < 0.05) and being unemployed (p = 0.001). Risk of PTSD was significantly higher for survivors diagnosed at ages 15 to 20 years (p < 0.05). PTSD was more common among survivors treated with intensive chemotherapy (p < 0.05) or radiation therapy (p < 0.001) and who relapsed or developed a second malignant neoplasm (p < 0.001). Neuroblastoma and Wilms tumor survivors had a significantly lower risk of PTSD than did leukemia survivors (p < 0.05). Conclusions: While the majority of childhood cancer survivors did not demonstrate PTSD, a clinically significant number did meet diagnostic criteria. Prospective assessment of survivors with high risk demographic-, diagnosis-, and treatment-related characteristics should be considered as part of long-term health screening. No significant financial relationships to disclose.
Final STEPP results of prophylacatic versus reactive skin toxicity (ST) treatment (tx) for panitumumab (pmab)-related ST in patients (pts) with metastatic colorectal cancer (mCRC)
Authors: Mitchell E. P. , Lacouture M. , Shearer H. , Iannotti N. , Piperdi B. , Pillai M. , Xu F. , Yassine M. 
Published: February 2017

CRA4027 Background: Pmab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is approved as monotherapy in the US for mCRC following disease progression (PD) and in the EU and Canada for tumors bearing wild-type (WT) KRAS. The most common toxicity with anti-EGFR inhibitors are ST. This study of pmab+ chemotherapy (CT) estimates the difference in the incidence of specific ≥ grade 2 ST of interest between pts receiving prophylactic (P) or reactive (R) skin tx. Methods: Pts had unresectable mCRC after PD with 1st-line fluoropyrimidine and oxaliplatin-based CT ± bevacizumab. Pts received either pmab 6.0mg/kg/FOLFIRI Q2W or pmab 9 mg/kg/irinotecan Q3W. Within each stratum, pts were randomized 1:1 to either P ST tx 24 hrs before the 1st dose daily for 6 wks or R ST tx after ST occurred. Tx for ST included: moisturizers, sunscreen, topical steroid, and doxycycline. Efficacy and safety were evaluated by P vs R tx groups, KRAS status (mutant [MT] vs WT), and chemotherapy status. Responses were assessed using modified RECIST with confirmation. Quality of life was assessed using the Dermatology Life Quality Index at screening, wks 2–7, and follow-up. Results: 95 pts were enrolled and randomized: 48 pts to P and 47 pts to R. During the 6 wk ST tx period, 29% of pts in the P group vs 62% of pts in the R group had protocol-specified ≥grade 2 ST. Of the 87 KRAS evaluable pts, 49 (56%) pts had WT KRAS and 38 (44%) pts had MT KRAS. Efficacy and safety are shown. Mean (SD) change in DLQI from baseline was 1.3 (2.6) for P and 4.2 (5.8) for R at wk 3 (when the median time to 1st ≥grade 2 ST was reached in the R group) and was 2.0 (2.8) for P and 2.6 (4.4) for R at wk 7. Conclusions: Prophylactic use of the skin tx regimen resulted in >50% reduction in the rate of specific ≥ grade 2 STs and improved QOL during the 6-week skin tx period vs R use. Numerical differences in favor of the P group were observed for all endpoints. [Table: see text] [Table: see text]
Partial breast irradiation or whole breast radiotherapy for early breast cancer: A meta-analysis of randomized controlled trials
Authors: Valachis A. , Mauri D. , Polyzos N. P. , Mavroudis D. , Georgoulias V. , Casazza G. 
Published: February 2017

CRA532 Background: The purpose of the study was to compare treatment outcomes in patients with breast cancer treated with partial breast irradiation and of those treated with whole breast radiation therapy. Methods: We conducted a systematic review and meta-analysis of published. Randomized clinical trials comparing partial breast irradiation versus whole breast radiation therapy. Primary outcome was overall survival and secondary outcomes were locoregional, distant and supraclavicular recurrences. Results: A search of the literature identified 3 trials with pooled total of 1,140 patients. We found no statistically significant difference between partial and whole breast radiation arms associated with death (OR 0.912, 95% CI 0.674–1.234, p = 0.550), distant metastasis (OR 0.740, 95% CI, 0.506–1.082, p = 0.120), or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278–7.202, p = 0.560). However, partial breast irradiation was statistically significantly associated with an increased risk of both local (pooled OR 2.150, 95% CI, 1.396–3.312; p = 0.001) and regional disease recurrences (pooled OR 3.430, 95% CI, 2.058–5.715; p < 0.0001) compared with whole breast radiation. Conclusions: Partial breast irradiation does not jeopardize survival and may be used as an alternative to whole breast radiation. Nevertheless, the issue of locoregional recurrence needs to be further addressed. No significant financial relationships to disclose.
A phase III study comparing concurrent gemcitabine (Gem) plus cisplatin (Cis) and radiation followed by adjuvant Gem plus Cis versus concurrent Cis and radiation in patients with stage IIB to IVA carcinoma of the cervix
Authors: Dueñas-González A. , Zarba J. J. , Alcedo J. C. , Pattarunataporn P. , Beslija S. , Patel F. , Casanova L. , Barraclough H. , Orlando M. 
Published: February 2017

CRA5507 Background: Cervical cancer is the second-most common cancer among women worldwide, in both incidence and mortality. Current standard therapy for locally advanced disease consists of concurrent Cis and external-beam radiation (XRT). This multicenter, open-label, randomized, phase III trial aimed to improve outcomes, capitalizing on the synergistic activity of Gem, Cis, XRT, and the potential value of adjuvant therapy. Methods: Eligible patients (pts) with bulky stage IIB to IVA, 18–70 years of age, chemotherapy- and radiotherapy-naive, with a Karnofsky Performance Status score ≥70, were randomized to Arm A: Cis 40 mg/m2 followed by Gem 125 mg/m2 weekly × 6 doses with concurrent XRT (50.4 Gy: in 28 fractions: 1.8 Gy/day, 5 days/week), followed by brachytherapy (brachy) (30–35 Gy) and then 2 adjuvant 21-day cycles of Gem (1,000 mg/m2 on Days 1 and 8) plus Cis (50 mg/m2 on Day 1); or Arm B: Cis 40 mg/m2 weekly × 6 doses with concurrent XRT followed by brachy, given as in Arm A. Primary endpoint was progression-free survival (PFS) at 3 years, compared between arms using Kaplan-Meier methods and a Z-statistic. Results: 515 pts were enrolled between 5/02 and 3/04 (259 pts Arm A, 256 pts Arm B). Median age was 46 years; stage IIB/IIIB/IVA in 61/37/2% of pts. Compliance in the concurrent and brachy phase was >90% for both arms; adjuvant cycles were completed by >75% of pts in Arm A. PFS at 3 years was 74% in Arm A compared to 65% in Arm B, resulting in a statistically significant improvement (p = 0.029). Overall survival (log-rank p = 0.0224) and time to progressive disease (log-rank p = 0.0008) were also significantly improved. Significantly more pts in Arm A experienced grade 3/4 toxicities (86.5%), compared to pts in Arm B (46.3%; Fisher's p < 0.001). In Arm A, 2 pts died due to causes probably related to treatment compared to 0 pts in Arm B. Conclusions: This novel regimen of concurrent Gem plus Cis and XRT followed by brachy and adjuvant Gem plus Cis significantly improved outcomes in pts with locally advanced carcinoma of the cervix, at the expense of increased but acceptable toxicity, compared to the current standard of care. [Table: see text]
MSH2 and adjuvant cisplatin-based chemotherapy in non-small cell lung cancer
Authors: Fouret P. , Planchard D. , Mendiboure J. , Kamal N. S. , Olaussen K. A. , Bertrand P. , Pirker R. , Dunant A. , Le Chevalier T. , Soria J. C. ,   IALT-Bio Investigators
Published: February 2017

CRA7502 Background: Adjuvant cisplatin-based chemotherapy improves survival among patients with non-small cell lung cancer. The human MutS homolog 2 (MSH2) protein is required to repair cisplatin-DNA lesions. Methods: We used immunohistochemistry to determine MSH2 expression in specimens from patients who had been enrolled in the International Adjuvant Lung Trial. The long-term (median follow-up 7.5 years) overall survival benefit was evaluated in a Cox model adjusted on clinical and pathological variables. Results: Among 673 evaluable tumors, 257 (38%) were MSH2 positive and 416 (62%) were MSH2 negative. The long-term survival benefit of chemotherapy was likely different according to MSH2 expression (test for interaction, P=0.06): chemotherapy compared with observation prolonged survival in the MSH2 negative group (adjusted hazard ratio for death, 0.76; 95%CI, 0.59 to 0.97; P=0.03), but not in the MSH2 positive group (adjusted hazard ratio for death, 1.12; 95%CI, 0.81 to 1.55; P=0.48). In the control arm, the adjusted hazard ratio for death associated with MSH2 positivity compared to MSH2 negativity was 0.66 (95%CI, 0.49 to 0.90; P=0.01). Among 658 patients with available excision repair cross-complementing group 1 (ERCC1) data, the benefit of chemotherapy decreased with the number of positive markers among MSH2 and ERCC1 (P=0.01). Chemotherapy compared with observation prolonged survival in the combined MSH2 negative/ERCC1 negative subgroup (adjusted hazard ratio for death, 0.65; 95%CI, 0.47 to 0.91; P=0.01). Conclusions: MSH2 appears to predict a long-term benefit from adjuvant cisplatin-based chemotherapy in patients with non-small cell lung cancer and may be combined with ERCC1. [Table: see text]
A randomized trial of chemoradiation using mitomycin or cisplatin, with or without maintenance cisplatin/5FU in squamous cell carcinoma of the anus (ACT II)
Authors: James R. , Wan S. , Glynne-Jones R. , Sebag-Montefiore D. , Kadalayil L. , Northover J. , Cunningham D. , Meadows H. , Ledermann J. ,   National Cancer Research Institute (NCRI) ACT II Trial Management Group
Published: February 2017

LBA4009 Background: Chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and mitomycin-C (MMC) is standard treatment for anal cancer. This trial addresses two questions: whether (i) replacing MMC with cisplatin (CDDP) improves the complete response (CR) rate, and (ii) two cycles of maintenance chemotherapy after CRT reduces recurrence. Methods: Between 2001 and 2008, 940 patients (pts) were recruited to a multicenter, randomized factorial trial. Pts received 5-FU (1,000mg/m2/day on d1–4 and 29–32), radiotherapy (RT) (50.4Gy in 28 fractions), and either MMC (12mg/m2, d1; n=471) or CDDP (60mg/m2 on d1 and 29; n=469). Pts were also randomized to receive maintenance therapy (n=448) 4 weeks after CRT (two cycles of CDDP and 5-FU weeks 11 and 14) or no maintenance (n=446). Maintenance randomization was not considered appropriate in 46 pts. Statistical power was ≥80% to detect a difference in the CR rate of 5% (CDDP vs MMC), and 30% reduction in recurrence (maintenance vs no maintenance). Results: Median age 58 yrs; 62% male, 38% female; tumor site - canal (81%), margin (15%); stage T1-T2 (50%), T3-T4 (43%); node negative (62%), positive (30%). Median follow-up was 3 yrs. The CR rate was 94% MMC and 95% CDDP (p=0.53). MMC pts had more acute grade 3/4 haematological toxicities (25 vs 13%, p<0.001) but this did not result in an increase in neutropaenic sepsis (3.1 vs 3.2%, p=0.93). Non-haematologic grade 3/4 toxicities were similar (61 vs 65%, p=0.22). Preliminary analysis shows no statistically significant difference in recurrence free survival (RFS) (HR 0.89, 95% CI 0.68, 1.18; p=0.42) or overall survival (HR 0.79, 95% CI 0.56,1.12; p=0.19) for the maintenance comparison. The number of pre-treatment colostomies not reversed were similar between treatments (18 MMC vs 14 CDDP, p=0.65, Maint/No maint, p=0.23) and only 9 disease-free pts had colostomies performed (5 MMC, 4 CDDP). Conclusions: ACT II is the largest trial conducted in anal cancer. High CR (95%) and RFS (75% at 3 yrs) rates were achieved with this CRT. This excellent outcome may have been influenced by the absence of a gap in the RT schedule. There was no difference in CR rates between MMC and CDDP or in RFS rates with or without maintenance chemotherapy. 5-FU, MMC with RT remains the standard of care. [Table: see text]
A randomized, phase III study of carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in relapsed platinum-sensitive ovarian cancer (OC): CALYPSO study of the Gynecologic Cancer Intergroup (GCIG)
Authors: Pujade-Lauraine E. , Mahner S. , Kaern J. , Gebski V. , Heywood M. , Vasey P. , Reinthaller A. , Vergote I. , Pignata S. , Ferrero A. 
Published: February 2017

LBA5509 Background: This multicenter phase III study was designed to compare efficacy and safety of carboplatin-pegylated liposomal doxorubicin (PLD) (C-D) and carboplatin-paclitaxel (C-P) in relapsed platinum-sensitive OC patients (pts). Methods: Pts with recurrent OC > 6 months after first-line or second-line platinum-based therapy who had been pretreated with a taxane were randomized by stratified blocks to either C-D [C AUC 5 IV + PLD 30 mg/m2 IV] d1 q4 wk, or C-P [C AUC 5 IV + P 175 mg/m2 IV] d1 q3 wk × ≥ 6 cycles. The primary endpoint was progression-free survival (PFS), with secondary endpoints of toxicity, QoL and survival. The non-inferiority design required 745 events with 90% power, 95% confidence interval (CI). Results: From 4/05 to 09/07, 976 pts were enrolled, 467 to C-D arm and 509 to C-P arm. Pt parameters were well balanced. 85% of C-D and 78% of C-P pts received ≥ 6 cycles. Median follow-up is 21mo. Overall survival is still too early to be reported (n=308 deaths). This is the final analysis for PFS and toxicity. Results are below. Conclusions: This trial, the largest in relapsed OC, showed significant superiority of PLD-carboplatin combination in terms of PFS. In addition, compared to paclitaxel-carboplatin, PLD-carboplatin was well tolerated with lower rates of severe and long-lasting (neuropathy) toxicities. [Table: see text] No significant financial relationships to disclose.
A randomized, double-blind, placebo-controlled, phase IIIb trial (ATLAS) comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC)
Authors: Miller V. A. , O'Connor P. , Soh C. , Kabbinavar F. 
Published: February 2017

LBA8002 Background: B when added to chemotherapy, and E alone, each lead to improved survival in the treatment of patients (pts) with NSCLC (Sandler et al, NEJM 2006, 355:2542–2550; Shepherd et al, NEJM 2005, 353:123–132). Pre-clinical and clinical data (Herbst, J Clin Oncol 2007, 25: 4743–4750) suggest that the combination of B and E may improve the efficacy of NSCLC treatment. This potential was demonstrated in the BETA (B in combination with E compared with E alone for treatment of advanced NSCLC after failure of standard first-line chemotherapy) trial, a phase III trial in which progression free survival (PFS) was improved for patients treated with B + E (Hainsworth, Thoracic Oncol 2008, 3(11) Supp. 4:S302). Methods: The ATLAS study was designed to evaluate B + E (150 mg daily) versus B alone, following B + platin-containing doublet chemotherapy, in pts with stage IIIb/IV NSCLC. Enrolled pts were B-eligible, including pts with treated brain metastases, and pts anticoagulated with low molecular weight heparin(s). Pts with peripheral and/or extra-thoracic squamous tumors were also eligible. Pts received 4 cycles of B (15 mg/kg every 3 weeks) with chemotherapy. Pts who had not experienced disease progression (DP) or significant toxicity were then randomized to receive B + E or B + placebo (P). The primary objective of ATLAS was to compare PFS in pts receiving B + E versus B + placebo. Secondary objectives included the assessment of safety, and overall survival. A data safety monitoring committee (DSMC) monitored safety and efficacy. Results: 1,160 patients were enrolled and 768 randomized from May 2005 to May 2008. The DSMC recommended stopping the trial at the second planned interim efficacy analysis, because it met the primary endpoint. The median PFS after randomization was 4.8 mos for (B + E) vs. 3.7 mos for (B + P), HR= 0.722 (95% CI: 0.592–0.881), p = 0.0012. The safety profile for B + E was consistent with known profiles for B and E. Conclusions: E added to B treatment after chemotherapy with B significantly improves the PFS of patients treated in the first-line setting for locally advanced, recurrent, or metastatic NSCLC. [Table: see text]
Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).
Authors: Bang Y. , Kwak E. L. , Shaw A. T. , Camidge D. R. , Iafrate A. J. , Maki R. G. , Solomon B. J. , Ou S. I. , Salgia R. , Clark J. W. 
Published: February 2017

3 Background: PF-02341066 (PF-1066) is a selective, ATP-competitive, small molecule, orally bioavailable inhibitor of the ALK and MET/HGF receptor tyrosine kinases. EML4-ALK fusion oncogenes have been reported in approximately 4% of NSCLC. Patients with NSCLC harboring an ALK fusion were recruited into an expanded cohort at the recommended phase II dose within the first-in-patient monotherapy trial of PF-1066. Methods: Patients with ALK fusions, as determined by FISH using a break-apart probe to ALK, were enrolled into the expanded cohort irrespective of prior therapy. Treated brain metastases were allowed. PF-1066 was given orally at a dose of 250 mg BID. Responses were determined using RECIST with radiographic studies repeated every 8 weeks. The disease control rate (DCR) was determined based on the frequency of patients with RECIST CR, PR and stable disease at 8 weeks. Results: To date, 76 ALK+ NSCLC patients have been treated. The median number of prior treatments was 3 (range, 0-7). Most patients had adenocarcinoma histology and were never or former smokers. Mean plasma Ctrough was 292 ng/mL, which was above the predicted efficacious concentration from preclinical models (120 ng/mL). The median t1/2 was ∼53 hours. To date, 50 patients are evaluable for response; ORR is 64% and DCR 90%. The median progression-free survival is not yet mature. The median duration of treatment is 25.5+ weeks. Radiological responses typically were observed at the first or second restaging CT scan. Gastrointestinal toxicities, including nausea (55%) and vomiting (39%), were the most frequent adverse events. Conclusions: The oral ALK inhibitor, PF-1066, demonstrated a high response rate in patients selected for ALK fusions and was associated with a good safety profile. A phase III study has been initiated. This study supports the concept of molecular selection of NSCLC patients for appropriately designed treatment. [Table: see text]
Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study.
Authors: Burger R. A. , Brady M. F. , Bookman M. A. , Walker J. L. , Homesley H. D. , Fowler J. , Monk B. J. , Greer B. E. , Boente M. , Liang S. X. 
Published: February 2017

LBA1 Background: BEV, a humanized anti-VEGF monoclonal antibody, has demonstrated single-agent activity in patients with recurrent EOC, or PPC. The therapeutic impact of concurrent ± maintenance BEV with standard chemotherapy (CT) was evaluated in an international, double-blind, placebo-controlled phase III trial. Methods: Eligible patients had newly diagnosed, previously untreated EOC, PPC or FTC following abdominal surgery for staging and maximal effort at tumor debulking; stage III (macroscopic residual disease) or stage IV disease. The randomly allocated regimens were (1) CT (IV paclitaxel 175 mg/m2 + carboplatin AUC 6 cycles 1-6) + placebo cycles (C)2-22 (R1) (2) CT + concurrent BEV (15 mg/kg) C2-6 + placebo C7-22 (R2) (3) CT + concurrent BEV C2-6 + maintenance BEV C7-22 (R3) Infusions were administered d1 of a 21d cycle. The primary endpoint is progression-free survival (PFS) (radiographic, CA125, clinical criteria or death); secondary endpoints include overall survival, safety, and QoL. Results: 1,873 patients, median age 60, were enrolled from 9/05 - 6/09. Stage III optimally debulked (34%), stage III sub-optimally debulked (40%), and stage IV (26%) patients were similarly distributed in each treatment group. Grade 3 - 4 hypertension was reported in 1.6% (R1), 5.4% (R2), and 10.0% (R3). Grade ≥ 3 GI perforation, hemorrhage or fistula occurred in 0.8% (R1), 2.6% (R2) and 2.3% (R3). Relative to R1, the hazard of first progression or death for R2 was 0.908 (95% CI: 0.795 – 1.04, p=0.16) and for R3 was 0.717 (95% CI: 0.625 – 0.824, p<0.0001). Conclusions: This study demonstrates that front-line treatment of EOC, PPC, and FTC patients with CT plus concurrent and maintenance BEV prolongs PFS. This is the first anti-angiogenic agent to demonstrate benefit in this population. [Table: see text]