bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of computed tomography in the staging of patients with local-regional metastases of melanoma.
Authors: Buzaid A C , Tinoco L , Ross M I , Legha S S , Benjamin R S 
Published: February 2017

PURPOSE To determine the value of computed tomographic (CT) scans in the staging of asymptomatic melanoma patients who presented with or developed local-regional disease as the first site of recurrence and had both a normal chest radiograph and serum lactate dehydrogenase (LDH) level. PATIENTS AND METHODS The records of 99 patients with local-regional disease were reviewed. Of these, 89 met the study criteria and are the subjects of this analysis. Radiologic findings were categorized into the following four groups: (1) true-positive (TP), when the scan identified either regional or distant disease that was not appreciated on physical examination; (2) false-positive (FP), when the scan showed a radiologic abnormality that either did not change for at least 6 months or was proven to be histologically benign; (3) false-negative (FN), when a patient had symptoms suggestive of or suspicious for metastases and was subsequently found to have metastases, but all imaging studies were nondiagnostic; and (4) true-negative (TN), when all imaging studies were negative for metastases in an asymptomatic patient. RESULTS Findings on CT scan were TP for six patients (7%), FP for 20 (22%), and TN for 63 (71%). Of the six patients with TP findings, CT of the chest identified disease that was not visible on chest radiograph in only one and CT of the abdomen or pelvis showed metastases in five. CT or magnetic resonance imaging (MRI) of the brain showed no evidence of brain metastases in any patient, although it showed asymptomatic skull metastases in one patient. The most common FP findings were hypodense hepatic lesions and noncalcified lung nodules. CONCLUSION TP findings are observed in approximately 7% of patients with local-regional disease, which indicates a low yield but definite usefulness of CT scans in this subset of patients. Because FP are more common than TP findings, histologic diagnosis of recurrence is advisable. CT scan or MRI of the brain is not necessary in asymptomatic patients. CT of the chest adds little to a chest radiograph. In light of today's more cost-conscious health-care environment, our results are of practical importance.
Phase I trial of carboplatin and infusional cyclosporin in advanced malignancy.
Authors: Morgan R J , Margolin K , Raschko J , Akman S , Leong L , Somlo G , Scanlon K , Ahn C , Carroll M , Doroshow J H 
Published: February 2017

PURPOSE To determine the maximal-tolerated dose (MTD) of infusional cyclosporine (CSA) with fixed-dose carboplatin (CBDCA). PATIENTS AND METHODS Clonogenic cytotoxicity assays were performed to assess the effect of CSA on reversal of resistance to CBDCA. The phase I study was performed in three phases. In phases 1 and 2, escalating-dose CSA (5, 7.5, 8.8, or 9.5 mg/kg/d) with fixed-dose CBDCA 300 or 250 mg/m2 were administered. Phase 3 required an initial cycle of CBDCA 250 mg/m2 alone, followed by combination therapy with CBDCA 250 mg/m2 and CSA (8.8, 9.5, or 10.0 mg/kg/d). RESULTS Preincubation of platinum-resistant A2780 human ovarian cancer cells with CSA 2 micrograms/mL significantly enhanced CBDCA cytotoxicity in clonogenic assays. Fifty-one patients received 130 courses of therapy. The phase 1 MTD was thrombocytopenia (CSA 7.5 mg/kg/d and CBDCA 300 mg/m2) attributable to the effects of CBDCA alone. The phase 2 MTD was reversible nephrotoxicity (serum creatinine elevations to 3.6 and 4.4 mg/dL) and neutropenia (CSA 9.5 mg/kg/d and CBDCA 250 mg/m2). In phase 3, headache was observed in five patients and hypertension in one patient at CSA 10 mg/kg/d. The expected change in platelet count predicted for CBDCA alone was compared with the actual change; no excessive thrombocytopenia was observed with addition of CSA. Steady-state CSA levels of 2 micrograms/mL capable of reversing platinum resistance in vitro were observed. Four objective responses were observed. CONCLUSION CSA is effective in reversing CBDCA resistance in A2780 ovarian cancer cells. Short-term infusions of CSA < or = 8.8 mg/kg/d in combination with CBDCA are well-tolerated for heavily pretreated patients and result in CSA levels known to reverse CBDCA resistance in vitro.
Stage I testicular seminoma: results of adjuvant irradiation and surveillance.
Authors: Warde P , Gospodarowicz M K , Panzarella T , Catton C N , Sturgeon J F , Moore M , Goodman P , Jewett M A 
Published: February 2017

PURPOSE To assess the results of treatment and patterns of relapse in a contemporary group of patients with stage I testicular seminoma managed by adjuvant radiation therapy (RT) and surveillance. PATIENTS AND METHODS Between January 1981 and December 1991, 364 patients with stage I seminoma were treated at Princess Margaret Hospital. Of these, 194 were treated with adjuvant RT (92% received a dose of 25 Gy in 20 fractions for 4 weeks) and 172 were managed by surveillance. Two patients were included in this series twice--both had postorchiectomy RT for stage I disease, developed a contralateral seminoma, and were placed on surveillance and analyzed for outcome of both primary tumors. The median follow-up period for patients treated with adjuvant RT was 8.1 years (range, 0.2 to 12), and for patients managed by surveillance, it was 4.2 years (range, 0.6 to 10.1). RESULTS The overall 5-year actuarial survival rate for all patients was 97%, and the cause-specific survival rate was 99.7%. Only one patient died of seminoma. Of 194 patients treated with RT, 11 have relapsed, with a 5-year relapse-free rate of 94.5%. Prognostic factors for relapse included histology, tunica invasion, spermatic cord involvement, and epididymal involvement. Twenty-seven patients developed disease progression on surveillance, which resulted in a 5-year progression-free rate of 81.9%. The only factor identified to predict progression on surveillance was age at diagnosis: patients aged < or = 34 years had a 26% risk of progression at 5 years, in contrast to a 10% risk of progression in those greater than 34 years of age. CONCLUSION The outcome of patients with stage I testicular seminoma is excellent, with only one of 364 patients (0.27%) dying of disease. In our experience, both a policy of adjuvant RT and of surveillance resulted in a high probability of cure. Our surveillance experience showed that four of five patients with stage I seminoma are cured with orchiectomy alone. The benefit of adjuvant RT was reflected in a decreased relapse rate. We have identified a number of prognostic factors for relapse in patients managed with both approaches, but further study of prognostic factors is required, particularly to identify patients at high risk of disease progression on surveillance.
Consolidation chemoradiotherapy and autologous bone marrow transplantation versus continued chemotherapy for metastatic neuroblastoma: a report of two concurrent Children's Cancer Group studies.
Authors: Stram D O , Matthay K K , O'Leary M , Reynolds C P , Haase G M , Atkinson J B , Brodeur G M , Seeger R C 
Published: February 2017

PURPOSE To compare event-free survival (EFS) for patients with stage IV neuroblastoma who were treated with induction chemotherapy followed by additional courses of the same chemotherapy or by intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT). METHODS Two hundred seven children who were diagnosed with stage IV neuroblastoma after 1 year of age were given five to seven courses of induction chemotherapy consisting of cisplatin, etoposide, doxorubicin, and cyclophosphamide (CCC-321-P2). This chemotherapy was continued for 13 total courses for some patients, whereas intensive chemoradiotherapy with ABMT was given to others (CCG-321-P3). The decision to continue chemotherapy versus to consolidate with chemoradiotherapy was not randomized but was made by parents and physicians. Marrow used for ABMT was purged ex vivo and was free of immunocytologically detectable neuroblastoma cells. RESULTS One hundred fifty-nine of 207 patients (77%) remained event-free during induction therapy. Of these, 67 received chemoradiotherapy/ABMT (CCG-321-P3) and 74 continued chemotherapy (CCG-321-P2). Using Cox regression analysis, the relative risk (RR) of an event after chemoradiotherapy/ABMT was estimated to be 58% of that for patients who continued chemotherapy (P = .01). Similarly, Kaplan-Meier analysis estimated EFS at four years for the chemoradiotherapy/ABMT and chemotherapy groups to be 40% and 19% respectively (P = .019). Subgroups appearing to benefit from chemoradiotherapy/ABMT were those with only a partial tumor response to induction chemotherapy (RR = 0.43; P = .008; EFS, 29% v 6%) and those whose tumors had amplification of the N-myc gene (RR = 0.26; P = .112; EFS, 67% v 0%). CONCLUSION Consolidation with intensive, myeloablative chemoradiotherapy followed by purged ABMT may be more effective than continuing chemotherapy for patients with stage IV neuroblastoma.
Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment
Authors: Poultsides G. A. , Servais E. L. , Saltz L. B. , Patil S. , Kemeny N. E. , Guillem J. G. , Weiser M. , Temple L. K. , Wong W. , Paty P. B. 
Published: February 2017

CRA4030 Background: In the absence of symptoms (bleeding, perforation, obstruction) or resectable metastatic disease, primary tumor resection in patients who present with synchronous metastatic colorectal cancer (CRC) is of uncertain benefit. The purpose of this study was to describe the frequency of intervention necessary to palliate the intact primary tumor in patients who present with synchronous stage IV CRC and receive up-front modern combination chemotherapy without prophylactic surgery. Methods: Using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (FOLFOX, IFL, or FOLFIRI) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. Results: Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (stent or radiotherapy), whereas 213 (89%) never required any direct symptomatic management for their intact primary. Of those, 47 (20%) ultimately underwent elective colon resection at the time of metastasectomy and 8 (3%) during laparotomy for hepatic artery infusion pump placement. Neither use of bevacizumab, location of the primary tumor in the rectum, or metastatic disease burden were associated with increased intervention rate. In addition, when included as a time-varying covariate in a Cox regression model, the need for emergent intervention did not correlate with overall survival. Conclusions: Most patients with synchronous stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease. [Table: see text]
Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors
Authors: Aubert R. E. , Stanek E. J. , Yao J. , Teagarden J. R. , Subar M. , Epstein R. S. , Skaar T. C. , Desta Z. , Flockhart D. A. 
Published: February 2017

CRA508 Background: Tamoxifen (TAM) is metabolized to its active form, endoxifen, by hepatic cytochrome P450 (CYP) 2D6. Diminished CYP2D6 function, both by genetic variation or concurrent use of pharmacologic inhibitors, can significantly reduce endoxifen plasma concentrations and may lead to reduced TAM effectiveness. Methods: We interrogated an integrated research database comprised of de-identified medical and pharmacy claims (Rx) data for 10.7 million U.S. health plan members to identify women with breast cancer (BrCa) new to TAM therapy in a 30-month period from 2003 to 2005, and investigated the risk of recurrent BrCa as a function of concurrent use of potent and moderate inhibitors of CYP2D6. Inclusion criteria were: greater than or equal to 24 months of follow-up data and adherence to TAM (medication possession ratio > 70%) over 2 years (N = 1,298). Disease recurrence was defined by BrCa ICD-9 codes or CPT codes for mastectomy, lumpectomy, lymph node dissection, or radiation therapy occurring at least 6 months after the index TAM Rx. Two study groups were identified: TAM alone (N = 945) or TAM + a CYP2D6 inhibitor concomitantly (N = 353). BrCa recurrence rates were compared using Kaplan-Meier analysis with log-rank test, and univariate hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards model. Results: The study groups were similar at baseline. Median age was 52 years (TAM) and 53 years (TAM + CYP2D6 inhibitor). Interventions performed in the TAM alone group included mastectomy in 54%, lumpectomy in 36%, and radiation therapy in 47%, and were 52%, 38%, 46%, respectively, in the TAM + CYP2D6 inhibitor group. Among women on a CYP2D6 inhibitor, the median duration of overlap with TAM was 255 days. Patients receiving TAM + a CYP2D6 inhibitor had a 2-year BrCa recurrence rate of 13.9% versus 7.5% in patients receiving TAM alone (HR 1.92, 95% CI 1.33–2.76, p < 0.001). Conclusions: Our findings support the presence of a clinically significant drug interaction between TAM and known CYP2D6 inhibitors. This resulted in a significant 1.9 fold higher BrCa recurrence within 2 years of initiating TAM therapy. [Table: see text]
Cancer screening in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS)
Authors: Nathan P. C. , Ness K. K. , Hudson M. M. , Mahoney M. , Ford J. S. , Landier W. , Armstrong G. , Henderson T. , Robison L. L. , Oeffinger K. C. 
Published: February 2017

CRA6501 Background: Childhood cancer survivors may develop a second malignant neoplasm (SMN) and require surveillance to detect new cancers. Methods: We surveyed survivors and siblings from the CCSS, a cohort study of patients who have survived ≥5 years after a diagnosis of childhood cancer from 1970–86. We assessed compliance with the American Cancer Society's (ACS) guidelines for surveillance mammography, colonoscopy and PAP smears, and compared them to a matched population comparison group drawn from the 2003 National Health Interview Survey. Further, we examined compliance with the Children's Oncology Group (COG) guidelines for more frequent colonoscopy, mammography and skin exams in survivors at high risk for cancers of the colon (≥30 Gy pelvic, abdominal or spinal radiation), breast (≥ 20 Gy breast radiation in females) or skin (any radiation). Proportions screened were compared between groups with adjusted generalized estimating equations or log-binomial regression models. Results: There were 8318 survivors (50.6% male, mean age at interview 31.2 ± 7.3 years), 2661 siblings and 8318 population controls. 141/829 (17.6%), 592/855 (70.4%) and 3362/3690 (92.6%) eligible survivors reported a colonoscopy, mammogram, or PAP smear per ACS guidelines. Survivors were less likely than siblings (odds ratio [OR] 0.30; 95% confidence interval [CI] 0.18–0.49) and population controls (OR 0.63; CI 0.50–0.80) to have a colonoscopy, and less likely than siblings to have a PAP smear (risk ratio [RR] 0.98; CI 0.97–0.99). However, they were more likely than siblings (RR 1.14; CI 1.03–1.27) and population controls (RR 1.05; CI 1.01–1.10) to have a mammogram. Among survivors at increased risk for a SMN, only 92/809 (11.4%) reported a colonoscopy within the COG recommended 5-year period, 164/537 (30.5%) reported a mammogram within a 1-year period and 1288/4833 (26.7%) reported a skin exam. Care at a cancer center was associated with mammography (RR 1.91; 95% CI 1.02–1.27) and skin exam (RR 1.55; 95% CI 1.22–196) in high-risk patients. Conclusions: Childhood cancer survivors are not screened adequately for SMNs. Surveillance is very poor amongst those at highest risk for colon, breast, or skin cancer. Survivors and their physicians need education about the importance of surveillance. No significant financial relationships to disclose.
National survey of physicians practice patterns: Fertility preservation and cancer patients
Authors: Quinn G. , Vadaparampil S. T. , Jacobsen P. , Lee J. , Lancaster J. , Bepler G. , Keefe D. L. , Albrecht T. L. 
Published: February 2017

CRA9508 Background: Addressing the impact of cancer treatment on fertility is a high priority in providing quality cancer care to patients of childbearing age. Evidence suggests less than 50% of patients receive adequate fertility information prior to cancer treatment. This study assessed the practice patterns of physicians and identified perceptions of barriers to communication about fertility. Methods: A 37 item survey was developed by a review of the literature and previous qualitative interviews. A random sample of physicians from the American Medical Association Masterfile was stratified by board specialty related to oncology. Three waves of surveys were distributed across the United States. The domains of the survey included demographics, knowledge, attitudes and practice behaviors related to FP with patients of childbearing age. Results: Of 1,979 physicians identified, a total of 613 physicians completed the survey, yielding a 33% response rate among oncologists. Oncologists with favorable attitudes towards FP were 4.9 times more likely to discuss the impact of cancer treatment on future fertility than those who have unfavorable attitudes. GYN or Medical/Hematological oncologists were 2.1 times more likely than other specialists to report feeling comfortable discussing FP with their patients. The majority of oncologists reported discussing FP with patients and indicated the primary barrier to discussion was a patient too ill to delay treatment. However, less than 25% of oncologists report referring patients for FP and only 38% report knowledge of the ASCO guidelines suggesting oncologists should discuss FP and refer all patients of childbearing age. Less than 25% of physicians surveyed reported distributing educational materials regarding FP. Conclusions: The majority of physicians in this survey report discussing FP; however they are not consulting specialists or providing educational materials to their patients. Future research will include the development of physician and nurse training curricula and interventions to facilitate discussion of FP between physicians and cancer patients. No significant financial relationships to disclose.
A phase III trial comparing mFOLFOX6 to mFOLFOX6 plus bevacizumab in stage II or III carcinoma of the colon: Results of NSABP Protocol C-08
Authors: Wolmark N. , Yothers G. , O'Connell M. J. , Sharif S. , Atkins J. N. , Seay T. E. , Feherenbacher L. , O'Reilly S. , Allegra C. J. 
Published: February 2017

LBA4 Background: The primary aim of this two-arm randomized prospective study was to determine whether mFOLFOX6 plus bevacizumab (mFF6+B) would prolong disease-free survival (DFS) compared to mFOLFOX6 (mFF6) alone. Methods: Between September 2004 and October 2006, 2,672 patients with follow-up (1,338 and 1,334 in respective arms) with stage II (24.9%) or III carcinoma of the colon were randomized to receive either mFF6 (oxaliplatin 85 mg/m2 IV d1, leucovorin 400 mg/m2 IV d1, 5-FU 400 mg/m2 IV bolus d1, and 5-FU 2400 mg/ m2 CI over 46 hrs (d1+2) q14d × 12 cycles) or mFF6+B (same mFF6 regimen + bevacizumab 5 mg/kg IV q 2 wks × 1 yr). The primary end point was DFS. Events were defined as first recurrence, second primary cancer, or death. Results: The median follow-up for patients still alive was 36 months. The hazard ratio (HR: FF6+B vs. mFF6) was 0.89; 95% CI (0.76=1.04); p=0.15. Data censored at intervals disclosed an initial benefit for bevacizumab that diminished over time: The smoothed estimate of the DFS HR over time indicated that bevacizumab significantly reduced the risk of a DFS event during the interval from 0.5 to 1.0 year. There was no evidence that patients receiving bevacizumab had a worse DFS compared to those receiving mFF6 alone following treatment. Conclusions: The addition of bevacizumab to mFF6 did not result in an overall statistically significant prolongation in DFS. There was a transient benefit in DFS during the one-year interval that bevacizumab was utilized. Consideration may be given to clinical trials assessing longer duration of bevacizumab administration. Supported by PHS grants U10CA-12027, -69974, -37377, and -69651 from the NCI and a grant from Genentech, Inc. [Table: see text] No significant financial relationships to disclose.
ESPAC-3(v2): A multicenter, international, open-label, randomized, controlled phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma
Authors: Neoptolemos J. , Büchler M. , Stocken D. D. , Ghaneh P. , Smith D. , Bassi C. , Moore M. , Cunningham D. , Dervenis C. , Goldstein D. 
Published: February 2017

LBA4505 Background: Adjuvant 5-FU/FA (ESPAC-1 trial) and GEM (CONKO-001 trial) provide improved survival for patients with resected pancreatic cancer compared to no chemotherapy. The aim of the ESPAC-3 (v2) trial was to compare 5FU/FA vs GEM to identify if either adjuvant chemotherapy was associated with a significantly better survival. Methods: Patients with an R0/R1 resection for pancreatic ductal adenocarcinoma were randomized (stratified for resection margin status and country) <8 weeks of surgery to receive either 5FU/FA (FA, 20 mg/m2, iv bolus injection followed by 5-FU, 425 mg/m2, iv bolus injection given 1–5d every 28 days) or GEM (1,000mg/m2 iv infusion 1d, 8d and 15d every 4 weeks) for 6 months. The primary outcome measure was overall survival; the secondary measures were toxicity, progression free survival and quality of life. 1,030 patients were needed to detect a 10% difference in 2-year survival rates with 90% power. Results: 1,088 patients from 16 countries were randomized from July 2000 to Jan 2007 (5FU/FA = 551, GEM = 537). Median (range) age was 63 (31–85) years; 598 (55%) were men. Median tumor size was 30 (20–350) mm; 384 (35%) were R1 resections; 777 (72%) were node positive; and 263 (25%) were poorly differentiated tumors. Final analysis was carried out on an intention to treat basis with a minimum of 2 years follow-up after 753 (69%) patients had died. Median (IQR) follow-up of 335 alive patients was 34.2 (27.1–43.4) months, equal across treatment groups. Median survival from resection of patients treated with 5FU/FA was 23.0 (95% CI: 21.1, 25.0) months and for patients treated with GEM this was 23.6 (95%CI: 21.4, 26.4) months. Log-rank analysis revealed no statistically significant difference in survival estimates between the treatment groups (c2LR=0.7, p=0.39, HRGEM=0.94 (95%CI: 0.81, 1.08)). There was no significant difference in the effect of treatment across subgroups according to R status (test of heterogeneity c21=0.3, p=0.56). Conclusions: This is the largest adjuvant trial ever conducted for pancreatic ductal adenocarcinoma and showed no significant difference in survival between adjuvant 5FU/FA and adjuvant GEM. [Table: see text]