bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and coexistence of KRAS, BRAF, PIK3CA, NRAS, TP53, and APC mutations in Indian colorectal cancer patients: Next-generation sequencing–based cohort study
Authors: Jauhri Mayank , Bhatnagar Akanksha , Gupta Satish , BP Manasa , Minhas Sachin , Shokeen Yogender , Aggarwal Shyam
Published: February 2017

Colorectal cancer incidences are on a rise in India. In this study, we have analyzed the mutation frequencies of six potential biomarkers, their coexistence, association with clinicopathological characteristics, and tumor location in Indian colorectal cancer patients. Next-generation sequencing was performed to identify mutations in the six potential biomarker genes using formalin-fixed paraffin-embedded tissue blocks of 112 colorectal cancer patients. The mutation frequency observed in KRAS, BRAF, PIK3CA, NRAS, TP53, and APC was 35.7%, 7.1%, 16.1%, 6.3%, 39.3%, and 29.5%, respectively. The significant associations of mutations were KRAS with age less than 60 years (p = 0.041), PIK3CA with males (p = 0.032), tumor stage I–II (p = 0.013), lack of metastasis in lymph nodes (p = 0.040), NRAS with rectum (p = 0.002), and APC with T2 stage of tumor growth (p = 0.013). No single patient harbored mutations in these six genes or any five genes simultaneously. Significance was noted in coexistence of KRAS with APC (p = 0.024) and mutual exclusion of KRAS with BRAF (p = 0.029). PIK3CA exon 9 was observed to be more frequently associated with KRAS mutations than PIK3CA exon 20 (p = 0.072). NRAS mutations were mutually exclusive with BRAF and PIK3CA mutations. As per our knowledge, this is the first next-generation sequencing–based biomarker study in Indian colorectal cancer patients. Frequent coexistence of gene mutations in pairs and triplets suggests that synergistic effect of overlapping mutations might further trigger the disease. In addition, infrequent coexistence of multiple gene mutations hints toward different signaling pathways for colorectal cancer tumorigenesis.
Puckish protesting in the Umbrella Movement
Authors: Gan Wendy
Published: February 2017

The civility of Hong Kong protesters during the 2014 Umbrella Movement was often remarked on. Rather less known were the more playful and witty dimensions to the protests. Humour has always been a familiar and febrile strand in Hong Kong protest culture: puns are immensely popular, as are parodies and moments of surreal comic juxtapositions and appropriations that then take a life of its own. This article will examine two examples of madcap levity in the Umbrella Movement, including the use of the ‘Happy Birthday’ song to counter vocal on-site critics and a later and more significant shift to the Shopping Revolution, with its play on the Mandarin phrase, 購物 gòu wù (to go shopping). Humour’s specific potency here comes from an irreverent revoicing that wrests control away from dominant discourses. By redirecting attention and power away from establishment voices, marginalized and local points of view are empowered. Given recent political developments, however, humour has receded more into the shadows; the structure of feeling has altered considerably.
Mobile phone use in intimate relationships: The case of youth in Botswana
Authors: Lesitaokana William O
Published: February 2017

Drawing upon qualitative research data of a study I carried out in Gaborone and Francistown, this article attempts to demonstrate that the mobile phone is ubiquitous and cultural technology which has become central to young people’s intimate relationships. In particular, the use of mobile phones in romantic relationships among urban youth in Botswana is evinced in two ways, both of which are clearly local and distinct. First, the mobile phone is useful to facilitate emotional intimacy through voice calls, text messages and social networking, thus serving as a substantial link between intimate partners. Second, through its cost value, the mobile phone is recognised as a perfect gift to express practical intimacy in romantic relationships. This study therefore suggests that, in the way it is used, the mobile phone influences youth to create or recreate mobile cultures, which are to some extent predicated on their traditional lifestyles.
High-Frequency Irreversible Electroporation: Safety and Efficacy of Next-Generation Irreversible Electroporation Adjacent to Critical Hepatic Structures
Authors: Siddiqui Imran A. , Kirks Russell C. , Latouche Eduardo L. , DeWitt Matthew R. , Swet Jacob H. , Baker Erin H. , Vrochides Dionisios , Iannitti David A. , Davalos Rafael V. , McKillop Iain H.
Published: February 2017

Irreversible electroporation (IRE) is a nonthermal ablation modality employed to induce in situ tissue-cell death. This study sought to evaluate the efficacy of a novel high-frequency IRE (H-FIRE) system to perform hepatic ablations across, or adjacent to, critical vascular and biliary structures. Using ultrasound guidance H-FIRE electrodes were placed across, or adjacent to, portal pedicels, hepatic veins, or the gall bladder in a porcine model. H-FIRE pulses were delivered (2250 V, 2-5-2 pulse configuration) in the absence of cardiac synchronization or intraoperative paralytics. Six hours after H-FIRE the liver was resected and analyzed. Nine ablations were performed in 3 separate experimental groups (major vessels straddled by electrodes, electrodes placed adjacent to major vessels, electrodes placed adjacent to gall bladder). Average ablation time was 290 ± 63 seconds. No electrocardiogram abnormalities or changes in vital signs were observed during H-FIRE. At necropsy, no vascular damage, coagulated-thermally desiccated blood vessels, or perforated biliary structures were noted. Histologically, H-FIRE demonstrated effective tissue ablation and uniform induction of apoptotic cell death in the parenchyma independent of vascular or biliary structure location. Detailed microscopic analysis revealed minor endothelial damage within areas subjected to H-FIRE, particularly in regions proximal to electrode insertion. These data indicate H-FIRE is a novel means to perform rapid, reproducible IRE in liver tissue while preserving gross vascular/biliary architecture. These characteristics raise the potential for long-term survival studies to test the viability of this technology toward clinical use to target tumors not amenable to thermal ablation or resection.
Robot manipulator identification based on adaptive multiple-input and multiple-output neural model optimized by advanced differential evolution algorithm
Authors: Ngoc Son Nguyen , Anh Ho Pham Huy , Thanh Nam Nguyen
Published: February 2017

This article proposes a novel advanced differential evolution method which combines the differential evolution with the modified back-propagation algorithm. This new proposed approach is applied to train an adaptive enhanced neural model for approximating the inverse model of the industrial robot arm. Experimental results demonstrate that the proposed modeling procedure using the new identification approach obtains better convergence and more precision than the traditional back-propagation method or the lonely differential evolution approach. Furthermore, the inverse model of the industrial robot arm using the adaptive enhanced neural model performs outstanding results.
Graph representation for two-dimensional scene understanding by the cognitive vision module
Authors: Bielecki Andrzej , Śmigielski Piotr
Published: February 2017

In this article, the cognitive vision module of an autonomous flying robot is studied. The problem of the scene understanding by the robot, which flies on the high altitude, is analyzed. In such conditions, the examined scene can be regarded as two-dimensional. It is assumed that the robot operates in the urban-type environment. The scene representation is stored in the neighborhood graph that collects data about the objects locations, shapes, and their spatial relations. The fragments of the scene are understood by the robot in the context of neighborhoods of the objects. It is shown that such information can be effectively used for recognition of the object, while many objects of similar shape exist in the scene. In the proposed recognition process, not only the information about the shape of the object is utilized but also the spatial relations with other objects in its close neighborhood are examined.
Bidirectional scale-invariant feature transform feature matching algorithms based on priority k-d tree search
Authors: Liu XiangShao , Zhou Shangbo , Li Hua , Li Kun
Published: February 2017

In this article, a bidirectional feature matching algorithm and two extended algorithms based on the priority k-d tree search are presented for the image registration using scale-invariant feature transform features. When matching precision of image registration is below 50%, the discarding wrong match performance of many robust fitting methods like Random Sample Consensus (RANSAC) is poor. Therefore, improving matching precision is a significant work. Generally, a feature matching algorithm is used once in the image registration system. We propose a bidirectional algorithm that utilizes the priority k-d tree search twice to improve matching precision. There are two key steps in the bidirectional algorithm. According to the case of adopting the ratio restriction of distances in the two key steps, we further propose two extended bidirectional algorithms. Experiments demonstrate that there are some special properties of these three bidirectional algorithms, and the two extended algorithms can achieve higher precisions than previous feature matching algorithms.
Knowing, being or doing? A comparative study on human service professionals’ perceptions of quality in day-to-day encounters with clients and students with intellectual disabilities
Authors: Ineland Jens , Hjelte Jan
Published: February 2017

What does it mean to decide, act and behave in a professional manner towards people with intellectual disabilities? This article analyses how professionals from three welfare organizations describe quality in daily encounters with people with intellectual disabilities. Four hundred and twenty-one respondents participated in the study. Our empirical data consisted of written excerpts exclusively. Findings revealed that quality in encounters with people with intellectual disabilities was associated with personal attributes, pertinent knowledge, professional actions and ideological awareness. Findings also show differences in responses, both quantitatively (frequency) and qualitatively (content), which seem to be associated with organization. This reflects that human service organizations, as normative environments, underpin ideas about relevance and appropriateness in day-to-day situations, forming actions and perceptions among its members. Our conclusion is that organizational context needs to be considered to enhance our knowledge on how different categories of professionals view quality and moral worth when working with people with intellectual disabilities.
Learning curves of elite car racers
Authors: Franceschini Giordano , Terzini Mara , Zanetti Elisabetta M
Published: February 2017

This work is focused on racing cars driver’s training. Nine different tracks are considered and six drivers. Each driver drives on every track and performs consecutive trial sessions on each track; each session is made of various laps, and lap times are fitted using an exponential model, yielding an estimate of the initial performance, the learning constant, and the asymptotic performance. According to results, the learning curve varies significantly among pilots and among tracks; all pilots reach their session asymptotic performance in less than nine laps. The asymptotic performance in consecutive trial sessions improves significantly, and it is strongly correlated to the initial session performance (r2 > 0.99). As a conclusion, it is more profitable to perform separated sessions made of few laps (less than 10) rather than performing a smaller number of longer sessions. Whenever the initial lap time stops decreasing systematically, trial sessions should end because the asymptotic performance is not likely to improve further.
LGBTQ Part 2
Authors: Perron Tracy , Kartoz Connie , Himelfarb Chaya
Published: February 2017

In addition to dealing with the normal challenges of being a teenager, many times LGBTQ youth have to deal with harassment, intimidation, and bullying on a daily basis as they disproportionately experience verbal and physical harassment while in school as a result of their sexual orientation and/or gender identity. This violence adversely affects these students’ health and well-being as reflected in the depression and suicide rate among LGBTQ youth. As Part 2 of a series in articles on caring for LGBTQ youth in a school setting, this article reviews specific health risks in this group of students. School nurses can help reduce disparities in health for LGBTQ youth by understanding risk for psychological consequences of bullying and advocating for a just and responsive social school culture. Implications for school nurses include educating school staff and families as well as providing prompt and appropriate referrals for necessary psychological care.
Amniotic Fluid Assessment: Amniotic Fluid Index Versus Maximum Vertical Pocket
Authors: Coombe-Patterson Jacquelyn
Published: February 2017

Amniotic fluid assessment is vital to fetal well-being. Accurately diagnosing an amniotic fluid abnormality can aid in the proper management of a pregnancy at risk for an adverse outcome. Sonography is the most common way to assess amniotic fluid volume throughout a pregnancy; however, the most accurate technique, amniotic fluid index or maximum vertical pocket, is yet to be determined. Dye-dilution techniques are the most accurate way to measure amniotic fluid volume, but they are invasive and can be performed only at the time of a cesarean delivery. Multiple studies have been performed to determine the accuracy of the amniotic fluid index and maximum vertical pocket methods when diagnosing amniotic fluid volume abnormalities. Based on the studies reviewed in this article, neither method stands out as superior to the other when it comes to diagnosing amniotic fluid abnormalities during pregnancy. However, the maximum vertical pocket should also always be considered when an amniotic fluid abnormality is suspected because the amniotic fluid index overdiagnoses amniotic fluid abnormalities, leading to increased rates of pregnancy intervention and the potential for adverse pregnancy outcomes.
Overexpression of p53 protein in a high-risk population of patients with superficial bladder cancer before and after bacillus Calmette-Guérin therapy: correlation to clinical outcome.
Authors: Lacombe L , Dalbagni G , Zhang Z F , Cordon-Cardo C , Fair W R , Herr H W , Reuter V E
Published: February 2017

PURPOSE

We have previously demonstrated that p53 overexpression is predictive of disease progression and survival in Ta, Tis, and T1 tumors. Instillation of Bacillus Calmette-Guérin (BCG) is now accepted to be the most efficient adjuvant therapy for superficial bladder carcinoma. The aim of this study was to determine if p53 status, assessed before and after intravesical BCG therapy, can predict clinical outcome in a high-risk population of patients with superficial bladder carcinoma.

MATERIALS AND METHODS

We examined 196 tissue specimens from 98 patients, obtained immediately before and after intravesical BCG therapy. The pretherapy population was composed of 22 Ta, 57 Tis, and 19 T1 tumors. After BCG, 66 specimens were TO and 32 had residual tumors. Nuclear p53 overexpression was analyzed in relation to time to disease progression and disease-specific survival.

RESULTS

The median follow-up duration was 44 months. The detection of nuclear p53 overexpression before BCG therapy did not predict response to BCG therapy. Pre-BCG p53 protein overexpression, response to BCG therapy, and pre-BCG stage were all independent markers of disease progression. In patients with residual disease after BCG therapy (nonresponders), multivariate analysis confirmed that posttherapy p53 overexpression was the only independent marker of disease progression.

CONCLUSION

In this high-risk population of patients with superficial bladder tumors, patients who have p53 nuclear overexpression in the tumor and stage T1 disease before BCG therapy are at high risk of disease progression. Furthermore, in the group of patients with residual disease after BCG therapy, p53 status is a better predictor of disease progression than post-BCG stage.
Efficacy and tolerance of vinorelbine and fluorouracil combination as first-line chemotherapy of advanced breast cancer: results of a phase II study using a sequential group method.
Authors: Dieras V , Extra J M , Bellissant E , Espie M , Morvan F , Pierga J Y , Mignot L , Tresca P , Marty M
Published: February 2017

PURPOSE

To assess the antitumor efficacy and safety profile of the combination of Fluorouracil (5FU) and vinorelbine given as first-line therapy to patients with advanced breast cancer.

PATIENTS AND METHODS

As defined in the seven consecutive steps of a phase II group sequential design, 63 patients received 5FU 750 mg/m2/d for 5 consecutive days as a continuous infusion and vinorelbine 30 mg/ m2 on days 1 and 5 as a short intravenous (I/V) infusion every 3 weeks.

RESULTS

Forty-one of 63 patients achieved an objective response, which allowed us to discontinue the study and reject a response rate less than 50% with a statistical power of 90%. The unbiased estimate of the response rate was 61.6%. Response rate did not differ significantly according to the following: (1) type of prior adjuvant therapy (none, n = 23; without anthracycline, n = 6; with anthracyline, n = 34); (2) site of metastatic disease; and (3) number of metastatic sites. The median time to progression was 8.4 months. The median response duration was 12.3 months, and the median duration of complete response (CR), from the first assessment of CR, was 7.3 months. The median overall survival time was 23 months (28.1 months for patients with a CR). The main toxicities (grades 3 and 4) were neutropenia (90% of patients), infection (12.7%), mucositis (37%), and constipation (9.5%). Nevertheless, treatment could be given on an outpatient basis to the majority of patients, and the median relative dose-intensity was 86%.

CONCLUSION

This phase II study, which used a group-sequential design, shows that the combination of 5FU and vinorelbine is an active and tolerable regimen for the treatment of first metastatic progression of breast cancer. It provides an alternative regimen for patients who have previously received anthracycline-based adjuvant chemotherapy or in whom anthracyclines cannot be used.
Prognostic significance of abnormal p53 accumulation in primary, resected non-small-cell lung cancers.
Authors: Nishio M , Koshikawa T , Kuroishi T , Suyama M , Uchida K , Takagi Y , Washimi O , Sugiura T , Ariyoshi Y , Takahashi T , Ueda R , Takahashi T
Published: February 2017

PURPOSE

This study was conducted to evaluate the prognostic significance of p53 abnormalities in primary, resected non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS

Methodologic validation of immunohistologic detection of p53 abnormalities in routine pathology sections was assessed using 31 lung cancer specimens for which p53 gene status was known from our previous molecular biologic studies. Applying the optimized cutoff value, we evaluated the prognostic significance of p53 abnormalities in an independent cohort of 208 NSCLC patients with complete follow-up data, whose resections were consecutively performed between January 1984 and December 1988.

RESULTS

Immunohistologic detection of p53 abnormalities appeared to be reliable and showed approximately 90% concordance with the p53 gene status. Using the selected cutoff value of 10%, 46% of 208 NSCLCs showed p53 abnormalities. There was no relationship between p53 abnormalities and clinical outcome in the entire cohort, which represented all histologic subtypes of NSCLC (P = .58). Based on the reasoning that the influence of p53 abnormalities may have been obscured by distinct biologic roles depending on histologic subtypes, we also separately analyzed subsets of patients with adenocarcinomas (n = 100) and with squamous cell carcinomas (n = 88) and found that it may be a useful prognosticator only in adenocarcinoma patients (P = .04).

CONCLUSION

p53 abnormalities are not a significant prognostic factor in primary, resected NSCLC when all histologic subtypes are combined, but may be a useful prognosticator for adenocarcinomas. Additional studies are warranted for further evaluation, specifically of adenocarcinomas.
Intravenous azidothymidine with fluorouracil and leucovorin: a phase I-II study in previously untreated metastatic colorectal cancer patients.
Authors: Falcone A , Danesi R , Dargenio F , Pfanner E , Brunetti I , Del Tacca M , Nethersell A B , Conte P F
Published: February 2017

PURPOSE

To determine the plasma pharmacokinetics and the maximum-tolerated dose (MTD) of intravenous (IV) azidothymidine (AZT) administered 90 to 120 minutes after fluorouracil (5-FU) and leucovorin and to preliminarily evaluate the antitumor activity of this combination in metastatic colorectal cancer.

PATIENTS AND METHODS

5-FU 500 mg/m2 IV bolus was administered once a week in the middle of a 2-hour infusion of leucovorin; AZT was given as a 90 to 120-minute IV infusion 60 minutes after 5-FU. Initial AZT dose was 0.5 g/m2, and it was escalated in successive cohorts of three patients by 0.5 to 2 g/m2.

RESULTS

Thirty-five chemotherapy-naive metastatic colorectal cancer patients were entered onto the study, and AZT doses ranged from 0.5 to 10 g/m2. The peak AZT plasma concentration increased from 21.9 to 995.6 micromol/L. The area under the concentration/time curve (AUC) also showed a progressive, but not linear increase from 40.34 to 3,108 h x micromol/L. The most relevant toxicity was diarrhea, which was severe in six patients (17%). Toxicities were not AZT-dose-related, except fpr hypotension, which occurred in patients treated at AZT doses > or = 7 g/m2 and became dose-limiting for AZT 10 g/m2. Among 34 assessable patients, 15 objective responses were observed (44%; 95% confidence interval 27 to 62), lasting a median of 44 weeks; five (15%) were complete.

CONCLUSION

AZT doses > or = 6 g/m2 administered IV over 90 to 120 minutes produce maximum plasma concentration and AUC similar to those previously reached in murine tumor models. Dose-limiting toxicity is hypotension, which occurs at AZT 10 g/m2. The recommended AZT dose for further studies is 8 g/m2. The combination of 5-FU plus leucovorin plus AZT is feasible with acceptable toxicities, and has promising activity in metastatic colorectal cancer.
Conditioning regimen-dependent disposition of cyclophosphamide and hydroxycyclophosphamide in human marrow transplantation patients.
Authors: Slattery J T , Kalhorn T F , McDonald G B , Lambert K , Buckner C D , Bensinger W I , Anasetti C , Appelbaum F R
Published: February 2017

PURPOSE

The pharmacokinetics of cyclophosphamide (CY) and 4-hydroxycyclophosphamide (HCY) were studied in 14 patients being prepared for bone marrow transplantation with either busulfan (BU)/CY (n = 7) or CY/total-body irradiation (TBI) (n = 7) to determine whether exposure to CY and its proximate toxic metabolite HCY is modulated by other agents used in the preparative regimen.

PATIENTS AND METHODS

HCY was assayed by a new method that stabilized the metabolite at bedside. In BU/CY patients (who also received phenytoin), CY clearance was 112% greater (P = .0014), half-life 54% less (P = .0027), peak HCY concentration in plasma/CY dose 113% greater (P = .0006), and the ratio of area under the plasma concentration-time curves (AUCs) of HCY to CY 166% greater (P = .0116) than in CY/TBI patients. The ratio of the AUC of HCY/CY dose was 48% greater in BU/CY patients than in CY/TBI patients when one CY/TBI patient with an apparent impaired ability to eliminate HCY was excluded from analysis. In CY/TBI patients, there was an inverse correlation between the AUC of HCY and that of CY (R2 = .740, P = .028). Also, the ratio of the AUC of HCY/CY dose was correlated with the average concentration of BU at steady-state (Css, Bu) (R2 = .646, P = 0.29). Variability in CY and HCY pharmacokinetics among the 14 patients overall was pronounced, with the highest variability (15-fold) observed in the ratio of the AUC of HCY to that of CY.

CONCLUSION

Prior administration of BU and/or phenytoin significantly alters exposure to CY and HCY. Interpatient variability in HCY exposure at a given CY dose is substantial.
Phase I dose-escalation trial of gemcitabine and cisplatin for advanced non-small-cell lung cancer: usefulness of mathematic modeling to determine maximum-tolerable dose.
Authors: Shepherd F A , Burkes R , Cormier Y , Crump M , Feld R , Strack T , Schulz M
Published: February 2017

PURPOSE

This study was undertaken to determine the maximum-tolerated doses of gemcitabine and cisplatin, each given weekly for 3 weeks with a 1-week rest.

PATIENTS AND METHODS

Patients less than 75 years of age were eligible if they had stage III/IV non-small-cell lung cancer (NSCLC), life expectancy > or = 12 weeks, hemoglobin level > or = 10 g/dL, granulocyte count > or = 2 x 10(9)/L, platelet count > or = 100 x 10(9)/L, hepatic enzymes < or = three times the upper limit of normal, and creatinine concentration < or = 130 mumoles/L. The starting doses for gemcitabine and cisplatin were 1,000 mg/m2 and 25 mg/m2 per week for 3 weeks. At dose level 2, cisplatin was increased to 30 mg/m2/wk for 3 weeks, and thereafter only gemcitabine was increased by 250 mg/m2/wk at each dose level to a maximum of 2,250 mg/m2/wk.

RESULTS

There were 33 men and 17 women, with a median age of 62 years. Pathology included adenocarcinoma in 35 patients, squamous in eight, large cell in six, and mixed histology in one. Sixteen patients had stage III and 34 had stage IV tumors. The median nadir granulocyte and platelet counts decreased with each dose level, but cycle 1 dose-limiting toxicity (DLT) in > or = two patients was not encountered in cycle 1, even at the highest dose level. Cumulative marrow toxicity was seen at all levels, which resulted in frequent dose reductions or omissions. A mathematic model of all toxicities over time suggested that dose level 4 (cisplatin 30 mg/m2/wk and gemcitabine 1,500 mg/m2/wk) would be the maximum dose at which grade 4 toxicity would be expected in < or = 33% of patients over four cycles. Of 47 assessable patients, 14 achieved a partial response (30%; confidence interval, 17% to 43%). The median duration was 16 weeks and the median survival time was 24 weeks (range, 3.5-64+).

CONCLUSION

Weekly gemcitabine and cisplatin are active against NSCLC, and the recommended phase II doses are 30 and 1,500 mg/m2/wk for 3 weeks, respectively.
Duration and reintroduction of adjuvant chemotherapy for node-positive premenopausal breast cancer patients.
Authors:   International Breast Cancer Study Group
Published: February 2017

PURPOSE

The optimal duration and timing of adjuvant chemotherapy for breast cancer patients remain uncertain and were prospectively studied.

PATIENTS AND METHODS

We randomly assigned 1,554 premenopausal breast cancer patients with node-positive disease in a 2 x 2 factorial design to receive the following: (A) cyclophosphamide, methotrexate, and fluorouracil for 6 consecutive courses on months 1 to 6 (CMF x 6); (B) CMFx6 plus three single courses of reintroduction CMF given on months 9, 12, and 15; (C) CMF for three consecutive courses on months 1 to 3 (CMFx3); or (D) CMFx3 plus three single courses of reintroduction CMF given on months 6, 9, and 12. Accrual was between July 1986 and April 1993. A total of 1,475 patients (95%) were eligible and assessable. The median follow-up duration was 60 months.

RESULTS

Patients who received CMFx3 without reintroduction had a 5-year disease-free survival (DFS) rate of 53% compared with 58% for the other three treatment groups (hazards ratio [HR], 1.20; 95% confidence interval [CI], 1.00 to 1.45; P = .04). The increased risk of relapse with CMFx3 was more marked for women aged less than 40 years (308 patients; HR, 1.32; 95% CI, 0.94 to 1.84; P = .11) and for patients with estrogen receptor (ER)-negative tumors (455 patients; HR, 1.45; 95% CI, 1.06 to 2.00; P = .02). Reintroduction chemotherapy provided additional benefit (HR, 0.86; 95% CI, 0.73 to 1.01; p = .07), especially for women > or = 40 years of age (1,167 patients; HR, 0.82; 95% CI, 0.68 to 0.99; P = .04).

CONCLUSION

Three courses of adjuvant CMF chemotherapy are not sufficient compared with longer duration CMF chemotherapy, especially in younger women and in patients with ER-negative primary tumors. Reintroduction chemotherapy showed some evidence of additional benefit, but remains investigational.
Paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a phase II trial.
Authors: Johnson D H , Paul D M , Hande K R , Shyr Y , Blanke C , Murphy B , Lewis M , De Vore R F
Published: February 2017

PURPOSE

Studies conducted by the Eastern Cooperative Oncology Group (ECOG) indicate both paclitaxel and carboplatin are associated with an improvement in 1-year survival in patients with stage IV non-small-cell lung cancer (NSCLC). Based on these findings, a phase II trial of these agents in combination was conducted in patients with advanced NSCLC.

PATIENTS AND METHODS

Eligibility included previously untreated stage IIIB or IV NSCLC patients with a good performance status (PS). Paclitaxel (135 or 175 mg/m2) was administered by 24-hour infusion on day 1, followed by a 1-hour infusion of carboplatin on day 2 (300 mg/m2 or dosed to an area under the concentration-time curve [AUC] of 6 mg/mL.min). Treatment was repeated every 28 days for a total of six cycles. Hematopoietic growth factors were not routinely used.

RESULTS

Among 51 eligible patients, there were no complete and 14 partial responses, for an overall response rate of 27% (95% confidence interval [CI], 17% to 41%). The median progression-free survival time was 23.8 weeks (range, 12.1 to 73.9) and median survival time, 38 weeks. The survival rate at 1 year was 32%. Grade 3 or 4 granulocytopenia and thrombocytopenia were observed in 47% and 3%, respectively, of the 184 treatment cycles administered. The most common nonhematologic toxicities included nausea and emesis, neuropathy, and arthralgia/myalgia.

CONCLUSION

Paclitaxel plus carboplatin is a moderately active regimen in patients with advanced NSCLC and warrants comparison with existing cisplatin-based regimens in a prospective randomized trial. The toxicities of this regimen are well tolerated in patients with a good PS.
Age and serum lactate dehydrogenase level are independent prognostic factors in human immunodeficiency virus-related non-Hodgkin's lymphomas: a single-institute study of 96 patients.
Authors: Vaccher E , Tirelli U , Spina M , Talamini R , Errante D , Simonelli C , Carbone A
Published: February 2017

PURPOSE

The role of classical pragnostic factors (ie, age, performance status [PS], stage, extranodal involvement, and serum lactate dehydrogenase [LDH] level) included in the International Index for diffuse large-cell non-Hodgkin's lymphoma (NHL) of the general population is presently unknown in the setting of human immunodeficiency virus (HIV). To assess the prognostic value of these factors in HIV-related NHL, we reviewed the cohort of patients with HIV-related NHL diagnosed and treated with combination chemotherapy (CT) at our institution.

PATIENTS AND METHODS

Ninety-six patients with systemic HIV-related NHL diagnosed and treated with combination CT regimens between September 1987 and December 1993 at the Centro di Riferimento Oncologico, Aviano, Italy, were studied. All clinical and laboratory data were evaluated by univariate and multivariate analyses, using overall survival as the end point.

RESULTS

Complete remission (CR) occurred in 48% of patients; the overall median survival and disease-free survival times were 7 and 13 months, respectively. Among the classical and HIV-related prognostic factors, the following had a statistically significant influence on survival: PS > or = 2, elevated LDH level, age greater than 40 years, a CD4 cell count less than 100/microL, active opportunistic infections at diagnosis of NHL, and B symptoms. Multivariate analyses showed that only age, serum LDH level, and CD4 cell count were independent predictors of shortened survival. The increased hazard for patients greater than 40 years of age was 1.6 (95% confidence interval [CI], 1.2 to 2.3), for patients with increased LDH it was 1.8 (95% CI, 1.01 to 3.1), and for patients with a CD4 cell count less than 100/microL it was 1.7 (95% CI, 1.01 to 2.9).

CONCLUSIONS

Our study shows that in addition to HIV-related prognostic factors, ie, CD4 cell count less than 100/microL, classical prognostic factors such as age and serum LDH level are independent prognostic factors and should be included in the design of future clinical trials of HIV-related NHL.
Transdermal Clonidine for Ameliorating Tamoxifen-Induced Hot Flashes
Authors: Goldberg Richard M. , Loprinzi Charles L. , O'Fallon Judith R. , Veeder Michael H. , Miser Angela W. , Mailliard James A. , Michalak John C. , Dose Ann Marie , Rowland Ken M. , Burnham Nora L.
Published: February 2017

The 1994 report by Goldberg et al, entitled "Transdermal Clonidine for Ameliorating Tamoxifen-induced Hot Flashes" (J Clin Oncol 12:155–158), included an incorrect version of Figure 1. The correct figure is as follows:

Please see the PDF for Figure.
Neurotoxicity and ototoxicity of cisplatin plus paclitaxel in comparison to cisplatin plus cyclophosphamide in patients with epithelial ovarian cancer.
Authors: Cavaletti G , Bogliun G , Crespi V , Marzorati L , Zincone A , Marzola M , Rota S , Galli A , Tredici P , Tredici G
Published: February 2017

PURPOSE

To compare the neurotoxicity and ototoxicity of combination cisplatin plus paclitaxel versus cisplatin plus cyclophosphamide using extensive clinical and instrumental evaluation.

PATIENTS AND METHODS

Forty-six of 51 consecutive patients affected by-epithelial ovarian cancer seen in our institution between October 1994 and August 1995 entered the study. After randomization, they were assigned to receive cisplatin 75 mg/m2 every 3 weeks associated with cyclophosphamide 750 mg/m2 (CC group, n = 22) or paclitaxel 175 mg/m2 over a 3-hour infusion (CP group, n = 24). Treatment was repeated six times in 43 patients and nine times in 25. Before treatment and after three, six, and nine courses of chemotherapy, patients underwent clinical and instrumental neurologic and otologic examinations.

RESULTS

Mild sensory impairment was evident even after only three courses of both treatments and signs and symptoms were more severe at the end of treatment. On clinical grounds only, it was possible to demonstrate after six and nine courses a difference between CC and CP treatment, due to the involvement in some CP patients of pain and thermal sensory modalities. However, the overall severity of the neuropathy was similar. Audiometric parameters demonstrated a more negative outcome after treatment in CC compared with CP patients. However, the different severity of the involvement was closely correlated to this initial difference in audiologic performance.

CONCLUSION

Up to nine courses of chemotherapy, the CC and CP schedules are similar in terms of severity of neurotoxicity and ototoxicity when patients are evaluated during and immediately after treatment. With the doses used in our study, these toxicities are not dose-limiting. Our results suggest that most of the toxic effects observed during the treatment were due to cisplatin.
Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma.
Authors: Guillou L , Coindre J M , Bonichon F , Nguyen B B , Terrier P , Collin F , Vilain M O , Mandard A M , Le Doussal V , Leroux A , Jacquemier J , Duplay H , Sastre-Garau X , Costa J
Published: February 2017

PURPOSE

Several histologic grading systems have been validated in soft tissue sarcomas (STS), but no system is currently accepted worldwide. The National Cancer Institute (NCI) and French Federation of Cancer Centers Sarcoma Group (FNCLCC) systems were examined comparatively in the same population of patients with STS to determine which system is the best prognosticator with regard to metastasis development and tumor mortality.

PATIENTS AND METHODS

Four hundred ten adult patients with nonmetastatic STS were examined. Histologic grade was established according to the NCI and FNCLCC systems in each case. The prognostic value of both systems was examined using univariate and multivariate (Cox's model) analyses, and special attention was devoted to tumors with discordant grades.

RESULTS

In univariate analysis, both the NCI and FNCLCC systems were of prognostic value to predict metastasis development and tumor mortality. In multivariate analysis, high-grade tumors, irrespective of the system used, size > or = 10 cm, and deep location were found to be independent prognostic factors for the advent of metastases. Tumor grade had a higher predictive value than size or depth, and higher prognostic weight was assigned to the FNCLCC grading system in Cox models. Grade discrepancies were observed in 34.6% of the cases. An increased number of grade 3 STS, a reduced number of grade 2 STS, and a better correlation with overall and metastasis-free survival within subpopulations with discordant grades were observed in favor of the FNCLCC system.

CONCLUSION

The FNCLCC system showed slightly increased ability to predict distant metastasis development and tumor mortality. The use of this system to evaluate STS aggressiveness might be favored.
Phase I trial and pharmacokinetic study of all-trans-retinoic acid administered on an intermittent schedule in combination with interferon-alpha2a in pediatric patients with refractory cancer.
Authors: Adamson P C , Reaman G , Finklestein J Z , Feusner J , Berg S L , Blaney S M , O'Brien M , Murphy R F , Balis F M
Published: February 2017

PURPOSE

To determine the maximum-tolerated dose (MTD) of all-trans-retinoic acid (ATRA) administered on an intermittent oral schedule with interferon-alpha2a (IFN-alpha2a) in children with refractory cancer, and whether the marked reduction in plasma ATRA concentrations observed with chronic daily oral dosing could be circumvented with an intermittent dosing schedule.

PATIENTS AND METHODS

Thirty-three children with refractory cancer (stratified by age, < or = 12 and > 12 years) were treated with ATRA 3 consecutive days per week and IFN-alpha2a 3 x 10(6) U/m2 5 consecutive days per week, both repeated weekly. The starting dose of ATRA was 60 mg/m2/d divided into three doses, with planned escalations to 90 and 120 mg/m2/d. Because severe headaches have been noted to occur on the initial day of ATRA administration, only two of three doses of ATRA were administered on day 1 of each week.

RESULTS

Pseudotumor cerebri or dose-limiting headache was observed in two of five patients older than 12 years treated at the 120-mg/m2/d dose level and in one of six < or = 12 years at the 90-mg/m2/d level. Other non-dose-limiting toxicities of ATRA included reversible elevations in hepatic transaminases and triglycerides, dry skin, cheilitis, and nausea/vomiting. One child with recurrent neuroblastoma had an objective response of 6 months' duration, and one with recurrent Wilms' tumor had histologic maturation of multiple tumors. This intermittent schedule allowed for exposure to relatively high plasma concentrations of ATRA on a repetitive basis. Following 30-mg/m2 doses, the ATRA area under the concentration-time curve (AUC) decreased from 96 +/- 14 micromol/L/min on day 1 to 26 +/- 24 micromol/L/min by day 3 of drug administration, but on day 1 of the fourth consecutive week of therapy, the AUC averaged 110 +/- 16 micromol/L/min. The recommended pediatric phase II dose of ATRA administered on this schedule is 90 mg/m2/d.

CONCLUSION

An intermittent schedule of ATRA administration appears to circumvent the low plasma drug exposure that is a result of the sustained upregulation of metabolism when this drug is administered on a chronic daily schedule. Based on the results of this trial, a phase II trial of ATRA/IFN-alpha2a in neuroblastoma and Wilms' tumor using this schedule is in progress.
Alternating MOPP and ABVD chemotherapy plus mantle-field radiation therapy in patients with massive mediastinal Hodgkin's disease.
Authors: Longo D L , Glatstein E , Duffey P L , Young R C , Ihde D C , Bastian A W , Wilson W H , Wittes R E , Jaffe E S , Hubbard S M , DeVita V T
Published: February 2017

PURPOSE

To evaluate the efficacy and toxicity of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy plus mantle-field radiation therapy in the treatment of patients with massive mediastinal Hodgkin's disease of any stage.

PATIENTS AND METHODS

Eighty patients presented with Hodgkin's disease and a mediastinal mass greater than one third the greatest chest diameter on chest radiograph. Patients were staged and treated with MOPP alternated with ABVD chemotherapy for a total of six cycles. Patients then received 10 Gy mantle-field radiation therapy delivered to the original extent of disease followed by 25 to 35 Gy to the residual abnormalities.

RESULTS

The complete response (CR) rate was 89%. With a median follow-up duration of 10 years, disease-free survival of the complete responders is 78% at 15 years and overall survival is 75% at 15 years. For patients with stage I or II disease, disease-free survival was 76% at 15 years and overall survival was 79%; for those with stage III or IV disease, disease-free survival was 82% at 15 years and overall survival was 64%. Age, stage, sex, B symptoms, number of extranodal sites, lactate dehydrogenase (LDH) levels, erythrocyte sedimentation rate, and platelet count did not influence treatment outcome. Treatment-related pneumonitis was noted in 16% of patients (fatal in one), mainly in those older than age 35 years who received total doses of radiation therapy greater than 42 Gy. Fertility is more often preserved with MOPP/ABVD therapy than with MOPP chemotherapy and there appears to be less pulmonary and cardiac disease than with ABVD chemotherapy. Two patients have developed second solid tumors within radiation ports and one relapsed patient developed acute leukemia after MOPP salvage therapy.

CONCLUSION

MOPP/ABVD followed by mantle-field radiation therapy is an effective treatment for all stages of Hodgkin's disease that present with a large mediastinal mass. Our data suggest that the large mediastinal mass is a more dominant determinant of prognosis than Ann Arbor stage or other clinical prognostic factors.
Peripheral-blood stem-cell transplantation versus autologous bone marrow transplantation in Hodgkin's and non-Hodgkin's lymphomas: a new matched-pair analysis of the European Group for Blood and Marrow Transplantation Registry Data. Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
Authors: Majolino I , Pearce R , Taghipour G , Goldstone A H
Published: February 2017

PURPOSE

To address the question of short-term and long-term advantages of peripheral-blood stem-cell transplantation (PBSCT) over autologous bone marrow transplantation (ABMT), we have reviewed the data of 3,214 patients with lymphoma, 2,859 undergoing ABMT, and 355 undergoing PBSCT.

PATIENTS AND METHODS

Analysis of prognostic factors for progression-free survival (PFS) was conducted separately for non-Hodgkin's lymphoma (NHL) (N = 1,915) and Hodgkin's disease (HD) (N = 1,299). In multivariate analysis, the relevant factors were status at transplant for NHL and sex, size of largest mass at transplant, status at transplant, and conditioning regimen for HD. The pair analysis was carried out by matching NHL and HD patients separately by their prognostic factors. Additionally, NHL patients were matched for histology, whereas both HD and NHL patients were matched for date of transplant. With this method, 454 patients were matched in the NHL group and 256 were matched in the HD group.

RESULTS

The overall survival (OS) and PFS unexpectedy were better for ABMT versus PBSCT patients in the HD group (OS, 65.3% at 4 years for ABMT v 52.7% for PBSCT; P = .0198). There was no difference in OS or PFS in the NHL group (OS, 56.6% at 4 years for ABMT v 52.7% for PBSCT; P = .4148). The overall relapse or progression rate at 4 years for NHL was 42% after ABMT and 49.2% after PBSCT (P = .1220); for HD, it was 40% and 58.6%, respectively (P = .0164). Transplant-related mortality was lower, but not significantly, with PBSCT: 7.0% for ABMT versus 3.5% for PBSCT in NHL (P = .1356) and 7% for ABMT versus 4.7% for PBSCT in HD (P = .6056). Hematologic recovery occurred faster significantly with PBSCT irrespective of disease.

CONCLUSION

This study confirms the advantage of PBSCT in terms of hematopoietic reconstitution, but it fails to show any superiority in the long term. Poorer results for both progression free and overall survival observed in HD patients who are receiving PBSCT are unexplained and should be confirmed with randomized studies.
Mobilization of peripheral-blood progenitor cells with high-dose etoposide and granulocyte colony-stimulating factor in patients with breast cancer, non-Hodgkin's lymphoma, and Hodgkin's disease.
Authors: Copelan E A , Ceselski S K , Ezzone S A , Lasky L C , Penza S L , Bechtel T P , Klein J L , Hehmeyer D M , Scholl M D , Marshall D D , Elder P J , Risley G L , Avalos B R
Published: February 2017

PURPOSE

We analyzed the safety and effectiveness of high-dose etoposide (2 g/m2) followed by granulocyte colony-stimulating factor (G-CSF) as a peripheral-blood progenitor cell (PBPC) mobilization regimen and assessed extent of tumor reduction in patients with breast cancer, non-Hodgkin's lymphoma (NHL), and Hodgkin's disease (HD).

PATIENTS AND METHODS

One hundred sixty-nine consecutive patients who eventually underwent PBPC transplantation received treatment with high-dose etoposide (2 g/m2) followed by daily G-CSF (5 microg/kg).

RESULTS

This mobilization method was effective in nearly all patients. No patients died of mobilization-related complications. A 50% reduction in tumor size was seen in 19% of assessable patients with breast cancer, 44% of those with NHL, and 38% of those with HD. Hematopoietic recovery (HR) following transplantation occurred in all patients. Patients with > or = 4 x 10(6) CD34+ cells/kg engrafted with neutrophils at a median of 9 days after transplant and patients with at least 1.2 x 10(6) CD34+/CD33- cells/kg achieved platelet recovery at a median of 15 days.

CONCLUSION

Etoposide plus G-CSF is an effective and safe method for mobilization of PBPCs. Etoposide is an effective agent in tumor reduction in NHL and HD and is less effective in breast cancer. The substantially lower incidence of prior exposure to this agent compared with cyclophosphamide favors its use.