bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of UK and European Association of Urology (EAU) guidelines for kidney cancer management
Authors: Nicol David
Published: February 2017

Clinical practice frequently utilises guidelines on how specific conditions should be managed. For urologists in the UK a range of sources are used as guidelines for the management of kidney cancer. These include documents from national bodies such as the National Institute for Health and Care Excellence (NICE), professional bodies as well as those prepared by individual groups of clinicians within regional cancer networks. In this article the European Association of Urology (EAU) guidelines on renal cell carcinoma are compared to guidelines used in the UK for this disease. Broadly consistent variations exist related to regional practice patterns, funding and the currency of the various guidelines. A specific strength of the EAU guidelines is the regular updating of these allowing incorporation of new evidence. These however do not consider the funding model for healthcare of the UK which dictates the availability of some treatment modalities and thus in some areas are not applicable. Current guidelines for kidney cancer developed within the UK are inconsistent and often outdated in terms of evidence sources. Broader use of the EAU guidelines within the economic restrictions of healthcare in the UK may result in a more consistent practise utilising current evidence sources in the management of kidney cancer.
Adult Cells Combined With Platelet-Rich Plasma for Tendon Healing
Authors: Rubio-Azpeitia Eva , Sánchez Pello , Delgado Diego , Andia Isabel
Published: February 2017

Background:

The combination of cells with platelet-rich plasma (PRP) may fulfill tendon deficits and help overcome the limited ability of tendons to heal.

Purpose:

To examine the suitability of 3 human cell types in combination with PRP and the potential impact of the tenocyte-conditioned media (CM) to enhance tendon healing.

Study Design:

Controlled laboratory study.

Methods:

Tenocytes, bone marrow–derived mesenchymal stem cells, and skin fibroblasts were cultured in 3-dimensional PRP hydrogels supplemented or not with CM, and cell proliferation and migration were examined. The effect of tendon-derived CM on matrix-forming phenotype and secretion of inflammatory proteins was determined through their administration to mesenchymal stem cells, tendon, and skin fibroblasts by reverse transcription quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.

Results:

Differences were found in the matrix-forming phenotype between each of the cell types. The ratio of collagen I:collagen III was greater in bone marrow–derived mesenchymal stem cells than in skin fibroblasts and tenocytes. The bone marrow–derived mesenchymal stem cells expressed increased levels of cartilage-related genes than tenocytes or skin fibroblasts. The presence of the tenocyte-CM stimulated basic healing mechanisms including proliferation and chemotaxis in all cell types. In addition, the tenocyte-CM modified the matrix-forming phenotype of every cell type when cultured in PRP hydrogels. Each cell type secreted interleukin-6, interleukin-8, and monocyte chemotactic protein-1 in PRP hydrogels, but mesenchymal stem cells secreted less interleukin-8 and monocyte chemotactic protein-1 than tenocytes or skin fibroblasts.

Conclusion:

The tenocyte-CM combined with PRP stimulated tenogenesis in mesenchymal stem cells and in skin fibroblasts and reduced the secretion of inflammatory proteins.

Clinical Relevance:

Modifying the target tissue with PRP prior to cell implantation may optimize the effect of cell therapies. Skin fibroblasts and bone marrow–derived mesenchymal stem cells combined with PRP could be used to regenerate tendons.
Defending Farmers’ Seed Freedom
Authors: Shiva Vandana
Published: February 2017

This article is an eco-feminist approach to understanding sustainability and social change, and engages with issues such as why the homogenization of crop production is dangerous, why it is the multinational corporation seed industry that needs regulations and not the small farmers and how colonization is taking place through seed patents. It also documents the Navdanya movement for the protection of biological and cultural diversity, raises concerns about the ecological and health impacts of genetically modified organisms (GMOs), addresses the issue of farmers’ suicide in India after the introduction of Bt cotton in the country, addresses the ongoing fight against the US seed giant Monsanto for the illegal and unauthorized manner in which GMO has been introduced in India, and highlights farmers’ rights vis-à-vis the seed.
Ruminations of a Gandhian: Margaret Chatterjee
Authors: Prasad Sujata
Published: February 2017

This article is based on conversations the author had with nonagenarian Gandhian, Margaret Chatterjee, over the last one year. It is reflective of Chatterjee’s engagement with Gandhian philosophy—non-violence and satyagraha, drawn from influences in Gandhi’s life—and captures why she rejects the categorization of Gandhi as either a traditionalist or a modernist.
Hina Jilani on her Satyagraha for Women’s Rights in Pakistan
Authors: Kakoty Juanita
Published: February 2017

This piece is based on a conversation the author had with lawyer and human rights activist from Pakistan, Hina Jilani, in May 2016. It captures Jilani’s account of the ‘Satyagraha’ she has waged in her lifetime for the rights of women in her country; and as she narrates her story, she interweaves it with the ‘Satyagraha’ that shaped the women’s movement in Pakistan. One can read here about Jilani’s struggle for truth, for a human rights consciousness in a political climate of military regime; and how she challenged courts in the country to step outside the realm of conventional law and extend justice to women and girls. And in the process, learn that her struggle for truth has been intertwined with that of the women’s movement in the country.
Pretreatment serum squamous cell carcinoma antigen: a newly identified prognostic factor in early-stage cervical carcinoma.
Authors: Duk J M , Groenier K H , de Bruijn H W , Hollema H , ten Hoor K A , van der Zee A G , Aalders J G
Published: February 2017

PURPOSE

To investigate the prognostic value of pretreatment serum squamous cell carcinoma antigen (SCC-ag) levels in patients with cervical squamous cell carcinoma in relation to well-established conventional risk factors.

PATIENTS AND METHODS

Sera from 653 women treated for squamous cervical cancer between 1978 and 1994 were analyzed for the presence of SCC-ag and related to clinicopathologic characteristics and patient outcome using univariate and multivariate analyses.

RESULTS

Increased pretreatment SCC-ag levels correlated strongly with unfavorable clinicopathologic characteristics (International Federation of Gynecology and Obstetrics [FIGO] stages IB to IV [P < or = .00005]; stages IB and IIA: tumor size [P = .0236], deep stromal infiltration [P = .00009], and lymph node metastasis [P = .0001]). After multivariate analysis, elevated pretreatment serum SCC-ag levels (P = .001), lesion size (P = .043), and vascular invasion by tumor cells (P = .001) were independent predictors for the presence of lymph node metastases. In Cox regression analysis, controlling for SCC-ag, lesion size, grade, vascular invasion, depth of stromal infiltration, and lymph node status only the initial SCC-ag level had a significant independent effect on survival (P = .0152). Even in node-negative patients, the risk of recurrence was three times higher if the SCC-ag level was elevated before therapy.

CONCLUSION

The determination of pretreatment serum SCC-ag level provides a new prognostic factor in early-stage disease, particularly in patients with small tumor size. In future trials to assess the value of new treatment strategies, pretreatment serum SCC-ag levels can be used to help identify patients with a poor prognosis.
Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The International Collaborative Cancer Group.
Authors: Coombes R C , Bliss J M , Wils J , Morvan F , Espié M , Amadori D , Gambrosier P , Richards M , Aapro M , Villar-Grimalt A , McArdle C , Pérez-López F R , Vassilopoulos P , Ferreira E P , Chilvers C E , Coombes G , Woods E M , Marty M
Published: February 2017

PURPOSE

To determine whether a combination chemotherapy regimen that contains epirubicin (fluorouracil, epirubicin, and cyclophosphamide [FEC]) is superior to the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in premenopausal women with axillary node-positive operable breast cancer.

PATIENTS AND METHODS

The International Collaborative Cancer Group (ICCG) conducted a large randomized trial in which two alternative schedules were used according to participating center: CMF1 versus FEC1 and CMF2 versus FEC2.

RESULTS

Seven hundred fifty-nine patients were entered onto the trial. At a median follow-up time of 4.5 years, no significant benefit for the anthracycline-containing regimen was observed in terms of relapse-free (P = .61) or overall survival (P = .13). FEC1 and CMF1 appear to be of similar efficacy, but there is a suggestion that FEC2 may be superior to CMF2, since patients who received FEC2 had improved overall (P = .02) and relapse-free survival (P = .03) rates. Nausea and vomiting and alopecia were more common in the epirubicin-containing regimen (P = .001).

CONCLUSION

We conclude that the FEC2 regimen, in which epirubicin replaced the methotrexate in CMF, is the preferable adjuvant chemotherapy regimen for premenopausal patients with operable axillary node-positive breast cancer.
Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study.
Authors: Rivkin S E , Green S , O'Sullivan J , Cruz A B , Abeloff M D , Jewell W R , Costanzi J J , Farrar W B , Osborne C K
Published: February 2017

PURPOSE

To determine whether the addition of surgical ovariectomy to standard chemotherapy prolongs disease-free survival (DFS) and overall survival in premenopausal patients with estrogen receptor (ER)-positive operable breast cancer with positive axillary nodes.

PATIENTS AND METHODS

Three hundred fourteen premenopausal patients with ER-positive, node-positive breast cancer were enrolled between July 1979 and July 1989. Patients were stratified according to number of involved nodes and type of primary surgery and randomized to receive either of the following: (1) cyclophosphamide 60 mg/m2/d by mouth for 1 year, methotrexate 15 mg/m2 intravenously (i.v.) weekly for 1 year, fluorouracil (5-FU) 400 mg/m2 i.v. weekly for 1 year, vincristine .625 mg/m2 i.v. weekly for the first 10 weeks, and prednisone weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 (CMFVP); or (2) bilateral ovariectomy followed by CMFVP.

RESULTS

The median follow-up time is 7.7 years and the maximum 13.2 years. Treatment arms are not significantly different with respect to either survival or DFS (one-sided log-rank, P = .55 and .70, respectively). The 7-year survival rate is 71% on the CMFVP arm and 73% on CMFVP plus ovariectomy. No significant differences were observed in node or receptor level subsets.

CONCLUSION

We conclude that, in this study, the addition of ovariectomy did not improve results over chemotherapy alone in the treatment of premenopausal women with node-positive, ER-positive, operable breast cancer. Our sample size was too small to detect a small improvement. The death hazards ratio of CMFVP/CMFVP plus ovariectomy was 1.22 (95% confidence interval [CI], .79 to 1.89).
Randomized trial of a psychologic distress screening program after breast cancer: effects on quality of life.
Authors: Maunsell E , Brisson J , Deschênes L , Frasure-Smith N
Published: February 2017

PURPOSE

Although psychosocial intervention can reduce psychosocial distress following breast cancer, many women who are experiencing problems are not identified and offered additional help. This trial assessed effects on quality of life of psychologic distress screening among newly diagnosed, nonmetastatic breast cancer patients.

PATIENTS AND METHODS

From 1990 to 1992, all eligible patients in one regional breast cancer center were identified and offered study participation. Women in both control and experimental groups received brief psychosocial intervention from a social worker at initial treatment. The experimental group also had monthly telephone screening of distress levels using a brief, validated instrument, with additional psychosocial intervention offered only to those with high distress at screening.

RESULTS

Among 282 eligible patients, 89% were randomized and completed the study. Participants' psychologic distress levels decreased over the study period (P = .0001). However, no between-group differences were observed. Mean distress scores among control and experimental women at 0-, 3-, and 12-month interviews were 20.7 and 20.4, 15.5 and 15.0, and 14.6 and 13.5, respectively. No between-group differences were observed with respect to physical health, functional status, social and leisure activities, return to work, or marital satisfaction.

CONCLUSION

Our results indicate that, among patients who receive a minimal psychosocial intervention as part of their initial cancer care, a distress screening program does not improve quality of life. Minimal psychosocial intervention at initial treatment may be effective in reducing distress, thus making it difficult to obtain additional benefit from a screening program.
Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors.
Authors: Rustin G J , Newlands E S , Lutz J M , Holden L , Bagshawe K D , Hiscox J G , Foskett M , Fuller S , Short D
Published: February 2017

PURPOSE

No increase in second tumor incidence was found in a previous analysis of women treated with chemotherapy for gestational trophoblastic tumors (GTT). More patient years at risk enabled a further analysis of the risk of second tumors to be performed in the 1,377 women treated in this until up to 1990.

PATIENTS AND METHODS

Health questionnaires were returned on 93.3% of patients who successfully completed chemotherapy and were living in the United Kingdom. The remainder were flagged for death or developing further cancers by the Office of Population Census and Surveys and by the Thames Cancer Registry. Incidence density analysis was performed based on 15,279 person-years of observation available. Standardized incidence ratio (SIR) was used to estimate the relative risk (RR) of second tumors associated with the treatment. To calculate the expected number, the actual incidence rates observed by the Thames Cancer Registry during the same calendar period of observation were used.

RESULTS

An overall 50% excess of risk (RR = 1.5; 95% confidence interval [CI], 1.1 to 2.1; P < .011) was observed: there were 37 second tumors, when 24.5 were expected. For specific second tumors, the risk was significantly increased for myeloid leukemia (RR = 16.6; 95% CI, 5.4 to 38.9), colon (RR = 4.6; 95% CI, 1.5 to 10.7), and breast cancer when the survival exceeded 25 years (RR = 5.8; 95% CI, 1.2 to 16.9). The risk was not significantly increased among the 554 women receiving single-agent therapy (RR = 1.3; 95% CI, 0.6 to 2.1). Leukemias only developed in patients receiving etoposide plus other cytotoxic drugs.

CONCLUSION

This study suggests that there is a slight increased risk of second tumors after sequential or combination chemotherapy for GTT. This has become apparent since the introduction of etoposide and longer follow-up.
Geographic variation in the conduct of patient surveillance after lung cancer surgery.
Authors: Johnson F E , Naunheim K S , Coplin M A , Virgo K S
Published: February 2017

PURPOSE

Considerable variation among surgeons exists in the current practice of patient surveillance after lung cancer treatment. We evaluated whether geographic factors are responsible for this observed variation.

METHODS

Profiles of hypothetical patients suitable for postoperative surveillance and a detailed questionnaire based on the profiles were mailed to the 3,700 members of the Society of Thoracic Surgery (STS). The influence of the geographic location of the respondents on practice patterns was assessed among eight large metropolitan statistical areas (MSAs) with sufficient numbers of respondents, among nine broad geographic areas (United States census regions), and by the population size of the MSA from which the respondents reported.

RESULTS

There were 2,009 responses (54% return rate); 768 of those respondents both operate on and provide long-term follow-up care for lung cancer patients. There were sizeable effects of tumor-node-metastasis (TNM) stage and year postsurgery on practice patterns. Respondents from the Los Angeles/Long Beach MSA consistently had the highest frequency of follow-up test usage and those from the Tampa/St Petersburg MSA usually had the lowest. This held true for most testing modalities and was consistent across TNM stages I to III and years 1 to 5 postsurgery. Follow-up strategy was generally most intensive in the largest MSAs (population size, 2.5 to 10 million). The STS respondents from the Pacific US census region generally used the most intensive follow-up strategies and those from the East North Central and Mountain regions often used the least intensive. The differences disclosed in all three analyses were small.

CONCLUSION

There is marked variation among STS members in surveillance strategy, and the determinants of testing intensity are complex and interrelated. TNM stage and year postsurgery clearly affect follow-up practice; this analysis provides the first evidence that geographic setting has rather little effect on the surveillance strategies of clinicians.
Natural history and prognosis of untreated stage I epithelial ovarian carcinoma.
Authors: Ahmed F Y , Wiltshaw E , A'Hern R P , Nicol B , Shepherd J , Blake P , Fisher C , Gore M E
Published: February 2017

PURPOSE

The aim of this study was to investigate the independent significance of prognostic factors in stage I invasive epithelial ovarian cancer (EOC).

PATIENTS AND METHODS

Between 1980 and 1994, all patients with stage I EOC (borderline tumors excluded) following surgical resection were entered onto this study. No patient received adjuvant therapy and patients were monitored as follows: years 1 to 2-physical examination and serum CA125 every 3 months and computed tomographic (CT) scan every 6 months; years 3 to 5-physical examination and serum CA125 every 6 months and CT scan yearly; years 5 to 10-annual physical examination and serum CA125, with CT scan if clinically indicated.

RESULTS

A total of 194 patients entered the study. The median patient age was 54 years (range, 15 to 83), and the median follow-up duration 54 months (range, 7 to 157). Five-year survival rates were as follows: stage IA, 93.7%; stage IB, 92%; and stage IC, 84%. Multivariate analysis using Cox's regression identified grade (P < .001), presence of ascites (P = .05), and surface tumor (P < .01) as independent poor prognostic factors. International Federation of Gynecology and Obstetrics (FIGO) substage did not appear to have independent prognostic significance. Intraoperative capsule rupture was not found to be prognostically significant. The impact of pre-operative rupture remains unclear.

CONCLUSION

This is an important series, as no patient received adjuvant therapy, and represents the natural history of surgically resected stage I EOC.
Double dose-intensive chemotherapy with autologous stem-cell support for metastatic breast cancer: no improvement in progression-free survival by the sequence of high-dose melphalan followed by cyclophosphamide, thiotepa, and carboplatin.
Authors: Ayash L J , Elias A , Schwartz G , Wheeler C , Ibrahim J , Teicher B A , Reich E , Warren D , Lynch C , Richardson P , Schnipper L , Frei E , Antman K
Published: February 2017

PURPOSE

Twenty-one percent of responding metastatic breast cancer patients remain progression-free a median 50 months following one intensification cycle of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/ m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). This trial studied whether the sequence of high-dose melphalan followed by CTCb resulted in improved disease response and duration.

METHODS

Women with at least partial responses (PRS) to induction received melphalan (140 or 180 mg/ m2) with peripheral-blood progenitor cell (PBPC) and granulocyte colony-stimulating factor (G-CSF) support. They were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support.

RESULTS

Data on 67 women, at a median of 25 months from CTCb, were examined. After melphalan, 49 (73%) required admission for fever (89%), mucositis (35%), or infection (15%) (median stay, 8 days). All received CTCb. For the first 33 patients, the median days from start of melphalan to CTCb was 24. After liver toxicity (one death from venoocclusive disease [VOD]) developed in 11 patients during CTCb, the interval between intensifications was increased to 35 days without incident. Twenty-three patients (34%) are progression-free a median of 16 months post-CTCb. The median progression-free survival (PFS) and survival times for the whole group are estimated at 11 and 20 months, respectively.

CONCLUSION

Treatment with this sequence of high-dose melphalan followed by CTCb has not resulted in superior PFS to date, when compared with single-intensification CTCb. This report discusses factors related to patient selection, the role of induced drug resistance, and the schedule of administration of alkylating agenting that may adversely influence outcome.
Improving the cancer chemotherapy use process.
Authors: Fischer D S , Alfano S , Knobf M T , Donovan C , Beaulieu N
Published: February 2017

PURPOSE

Reports of the tragic consequences of erroneous cancer chemotherapy overdoses at a prominent cancer center and a university hospital prompted a review of our institution's practices and those of 123 other hospitals to ascertain for each the current in-house process to prevent chemotherapy errors.

METHODS

A multidisciplinary committee of oncologists, nurses, and pharmacists reviewed the chemotherapy use process and identified opportunities for improvement. A 1-page facsimile survey was answered by 150 of 215 members of the American Society of Clinical Oncology (ASCO) who received it.

RESULTS

We further restricted the writing of cytotoxic chemotherapy orders to physicians who were board-certified or -eligible in hematology or medical, pediatric, and gynecologic oncology and their approved fellows. Dispensation of drugs is limited to oncology-certified pharmacists, and administration to chemotherapy-certified nurses. Standard orders are used either on special oncology forms or designated order sets in the computer. Procedures to regulate the ordering of antineoplastic drugs for nonmalignant indications by nononcology specialists are outlined. A process to prevent chemotherapy errors is in place in 95% of hospitals. Dedicated medical oncology units are ubiquitous, and most cancer centers and university hospitals have dedicated gynecologic and pediatric oncology units. Chemotherapy orders are generally written by oncology fellows and countersigned by an attending oncologist in cancer centers and university hospitals, whereas private oncology attending physicians write them in most community hospitals. Drugs are administered by oncology-certified nurses in most institutions.

CONCLUSIONS

These recommendations should improve the safety and effective use of chemotherapy and reduce the error rate to as close to zero as human fallibility will allow.
Treatment of cancer with radiation and drugs.
Authors: Tannock I F
Published: February 2017

PURPOSE

To review the current status and future prospects of combined treatment of cancer with radiation and drugs.

DESIGN

A review of (1) mechanisms whereby combined use of radiation and drugs might lead to improved therapeutic benefit for the treatment of cancer; (2) problems related to the design and analysis of clinical trials that evaluate combined modality treatment; and (3) clinical results of larger randomized trials that have compared combined versus single modality treatment for various types of cancer.

RESULTS

Improvement in the therapeutic index depends on exploitation of the biologic properties that differ between tumors and normal tissues; such properties may include mechanisms of resistance to radiation and drugs, tissue microenvironment, and cell proliferation or repopulation during radiotherapy. To detect or rule out the small but clinically important differences in outcome that might occur will require the performance of large, randomized, controlled trials or patient-based meta-analyses; single-arm studies, small randomized trials, and subgroup analyses of larger trials can generate hypotheses. Clinical gains from combined treatment have been demonstrated in a few sites, with disappointing results in others. In general, more promising results have accrued from concurrent treatment, despite greater toxicity, than from sequential use of drugs and radiation.

CONCLUSION

Clinical gains from combined treatment with radiation and drugs have been small. New, mechanistically based approaches to combined treatment are required.
Phase I/II trial of PIXY321 to enhance engraftment following autologous bone marrow transplantation for lymphoid malignancy.
Authors: Vose J M , Anderson J E , Bierman P J , Appelbaum F R , Anderson J R , Garrison L , Lebsack M E , Armitage J O
Published: February 2017

PURPOSE

A phase I/II study of PIXY321 following high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) was conducted to evaluate the safety and clinical potential of this agent.

PATIENTS AND METHODS

Fifty patients with Hodgkin's disease or non-Hodgkin's lymphoma (NHL) undergoing HDT and ABMT received PIXY321 post-ABMT in doses that ranged from 50 to 1,000 micrograms/m2/d either as intravenous (i.v.) or subcutaneous (SC) dosing until engraftment was reached.

RESULTS

If all doses are considered together, the median time to reach an absolute neutrophil count (ANC) > or = 500/microL was 18 days and the median time to platelet transfusion independence was 21 days. At the estimated optimum dose of 750 micrograms/m2/d by SC injection once daily, the median time to reach an ANC > or = 500/microL was 15 days and the median time to platelet transfusion independence was 16 days. Historical control patients who received granulocyte-macrophage colony-stimulating factor (GM-CSF) had a median time to an ANC > or = 500/microL of 19 days and a median time to platelet independence of 26 days.

CONCLUSION

The administration of PIXY321 post-ABMT was generally well tolerated and resulted in prompt engraftment in the majority of patients who underwent HDT and ABMT for lymphoid malignancies. The optimum dose and route of administration of PIXY321 suggested by this trial was 750 micrograms/m2/d by once-daily SC injection. Compared with historical control patients who received 2-hour i.v. GM-CSF, patients who received PIXY321 at 750 micrograms/m2/d by SC injection once daily had an improvement in the median days to neutrophil and platelet engraftment by 4 and 10 days, respectively.
Significance of cytogenetic findings for the clinical outcome in patients with T-cell lymphoma of angioimmunoblastic lymphadenopathy type.
Authors: Schlegelberger B , Zwingers T , Hohenadel K , Henne-Bruns D , Schmitz N , Haferlach T , Tirier C , Bartels H , Sonnen R , Kuse R
Published: February 2017

PURPOSE

The aim of this study was to evaluate the significance of cytogenetic findings for the clinical outcome of patients with Angioimmunoblastic Lymphadenopathy (AILD)-Type T-cell lymphoma.

MATERIALS AND METHODS

In a retrospective analysis, the cytogenetic findings of 50 patients with AILD-type T-cell lymphoma were correlated with the frequency of spontaneous and therapy-induced remissions and with survival using the statistical methods of Kaplan and Meier and the model of Cox for multivariate analysis. Treatment was not uniform because the patients were treated in different hospitals during a period of 8 years and because a standard therapy has not yet been established.

RESULTS

The following cytogenetic findings were associated with a significantly lower incidence of therapy-induced remissions and a significantly shorter survival duration: presence of aberrant metaphases in unstimulated cultures (P = .04 for both parameters); clones with an additional X chromosome (P = .0001 and P = .03, respectively); structural aberrations of the short arm of chromosome 1, preferentially involving 1p31-32 (P < .001 and P = .04, respectively); and complex aberrant clones with more than four aberrations (P = .0003 and P = .005, respectively). Multivariate analysis showed that these cytogenetic findings had a significant influence on survival, but therapy modalities did not. Only the presence of complex aberrant clones was an independent prognostic factor. Trisomy 3 had no effect on survival, but patients without trisomy 5 (P = .08) tended to live longer.

CONCLUSION

This is the first study that seems to indicate that cytogenetic findings have prognostic significance in AILD-type T-cell lymphoma. These results must be proven in prospective studies of homogeneously treated patients.
Inferior vena cava filters in cancer patients: indications and outcome.
Authors: Schwarz R E , Marrero A M , Conlon K C , Burt M
Published: February 2017

PURPOSE

Our experience with inferior vena cava (IVC) filter placement to prevent pulmonary emboli (PE) in cancer patients with deep vein thromboses (DVT) was reviewed to identify indications, patient characteristics, complications, and long-term outcome.

METHODS

Charts of 182 patients with cancer were retrospectively analyzed. All patients had received an IVC filter in our institution between January 1980 and April 1992.

RESULTS

Of 182 patients, 103 were men and 79 were women. Median age was 59 years (range, 15 to 88). Eight patients (4%) had stage I disease, 22 patients (12%) stage II, 37 patients (20%) stage III, and 115 patients (63%) stage IV. A DVT was diagnosed in 97 patients (53%), a PE in 46 patients (25%), and a combination in 39 patients (21%). Indications for IVC filter placement were DVT or PE in the presence of contraindications to anticoagulation therapy (perioperative, n = 58; CNS metastases, n = 20; thrombocytopenia, n = 7; bleeding, n = 61; others, n = 24; total, N = 170) or anticoagulation failure (recurrent PE, n = 6; recurrent DVT; n = 6; total N = 12). Filter placement complications (n = 6, 3%) included malposition (n = 3), migration (n = 1), arrhythmia (n = 1), and wound infection (n = 1), but no deaths. After filter placement, four patients developed a recurrent PE, and 11 patients developed a recurrent DVT. No significant postthrombotic complications were observed.

CONCLUSION

IVC filter placement patients with advanced cancer and thrombotic complications is safe, well tolerated, and can offer effective therapy/prophylaxis with a low incidence of treatment failure.
Tamoxifen-associated eye disease. A review.
Authors: Nayfield S G , Gorin M B
Published: February 2017

PURPOSE

The oral antiestrogen tamoxifen has demonstrated efficacy in the treatment of metastatic breast cancer and as adjuvant therapy in early-stage disease. Clinical trials of tamoxifen in chemoprevention of breast cancer among high-risk women have focused attention on potential adverse effects of long-term tamoxifen use, including the possibility of ocular toxicity. This review evaluates the published case reports, clinical series, and clinical trial data on ocular toxicities attributed to tamoxifen. Clinical issues of surveillance, differential diagnosis, and management of tamoxifen-related eye disease are discussed.

DESIGN

National Library of Medicine online bibliographic services were used to identify case reports and clinical studies of ocular adverse effects that occurred in patients receiving tamoxifen published through the fall of 1994. The medical literature relevant to issues raised by the reports and studies was similarly identified and reviewed.

RESULTS

Case reports and case series identify crystalline retinal deposits, macular edema, and corneal changes as potential tamoxifen ocular toxicities. Extensive retinal lesions and macular edema with visual impairment have been reported in a few patients receiving high-dose tamoxifen. Less extensive retinal changes may occur in patients receiving low doses for long periods, and isolated retinal crystals may be observed in patients without visual symptoms.

CONCLUSION

Ocular toxicity is uncommon in the current clinical setting of long-term, low-dose tamoxifen use. Physicians should be aware of the potential for ocular toxicity among patients receiving the drug and should assure appropriate surveillance and prompt evaluation of visual complaints.
Phase I and pharmacologic study of sequences of paclitaxel and cyclophosphamide supported by granulocyte colony-stimulating factor in women with previously treated metastatic breast cancer.
Authors: Kennedy M J , Zahurak M L , Donehower R C , Noe D A , Sartorius S , Chen T L , Bowling K , Rowinsky E K
Published: February 2017

PURPOSE

Pacltaxel is active in metastatic breast cancer, but limited information is available on combinations of this agent with other cytotoxic agents. Study aims were to determine the maximum-tolerated doses (MTDs) of paclitaxel (24-hour infusion) and cyclophosphamide (1-hour infusion) administered every 21 days with granulocyte colony-stimulating factor (G-CSF, filgrastim) to determine the effect of drug sequence on toxicity and pharmacology and to evaluate the activity of this combination in women with anthracycline-resistant disease.

PATIENTS AND METHODS

Thirty-seven women with metastatic breast cancer were treated. Starting doses were paclitaxel 135 mg/m2 and cyclophosphamide 750 mg/m2, with filgrastim 5 microG/kg/d subcutaneously beginning 24 hours after chemotherapy. Four patients were treated at each dose level. The sequence of drug administration was alternated between sequential patients, and with subsequent courses of therapy in each patient, to enable evaluation of effects of drug sequence on toxicity and pharmacology. Patients were treated every 21 days and disease status was reevaluated every two courses.

RESULTS

Paclitaxel 200 mg/m2 and cyclophosphamide 1,250 mg/m2 is the MTD for this combination on this schedule. The hematopoietic toxicity of therapy was sequence-dependent. Paired analysis of toxicity data indicated more severe toxicity in courses in which paclitaxel was administered first. Sequence-dependent pharmacologic effects did not account for this phenomenon. Responses were noted in 29% of patients with anthracycline-resistant disease.

CONCLUSION

Paclitaxel 200 mg/m2 and cyclophosphamide 1,250 mg/m2 with filgrastim administered every 21 days are the doses recommended for further study.
Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study.
Authors: McGuire W P , Blessing J A , Moore D , Lentz S S , Photopulos G
Published: February 2017

PURPOSE

Taxol (paclitaxel; Bristol-Myers Squibb, Princeton, NJ) is a new antineoplastic drug with broad-spectrum activity in solid tumors, including epithelial ovarian cancer, head and neck cancer, esophageal cancer, breast cancer, bladder cancer, and lung cancer. Its unique mechanism of action, polymerization of tubulin monomers, has stimulated both clinical and preclinical research on this agent. As limited drug supplies became more plentiful, a phase II trial of Taxol was initiated in patients with advanced squamous cervix cancer who had received no prior chemotherapy.

PATIENTS AND METHODS

In this trial, 30 assessable patients were initially entered onto the study and four partial responses were seen. Further accrual of 22 assessable patients was then accomplished to define better the response rate with smaller confidence intervals. The starting dose of Taxol was 170 mg/m2 (135 mg/m2 for patients with prior pelvic radiation) given as a 24-hour continuous intravenous infusion with courses repeated every 3 weeks. Dose escalations to 200 mg/m2 and deescalations to 110 mg/m2 were allowed based on adverse effects.

RESULTS

The final response rate was 17% (two complete responses and seven partial responses). The primary and dose-limiting toxicity was neutropenia.

CONCLUSION

The response rate makes Taxol a drug with sufficient activity to explore it in combination with other agents with similar activity.
Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer. Interim analysis of a phase II trial.
Authors: Stahl M , Wilke H , Fink U , Stuschke M , Walz M K , Siewert J R , Molls M , Fett W , Makoski H B , Breuer N , Schmidt U , Niebel W , Sack H , Eigler F W , Seeber S
Published: February 2017

PURPOSE

The prognosis of patients with locally advanced esophageal cancer (LAEC) remains poor when treated with local modalities. An intensive preoperative program with chemoradiotherapy was used to evaluate the curative resection rate, pathologic response, and survival of patients with LAEC.

PATIENTS AND METHODS

Ninety patients with LAEC were treated preoperatively with chemotherapy (three courses of fluorouracil, leucovorin, etoposide, and cisplatin [FLEP]) followed by concurrent chemoradiotherapy (one course of cisplatin plus etoposide in combination with 40 Gy of radiation). Transthoracic esophagectomy was performed 4 weeks after the end of radiation.

RESULTS

Seventy-two patients were included in this evaluation. Forty-four (61%) underwent a complete tumor resection, and 16 (22%) had no tumor in the resected specimen (pathologic complete response [PCR]). The operative mortality rate was 15%. At a median follow-up time of 22 months (range, 12 to 41), the median survival duration of all 72 patients was 17 months (range, 1 to 41+). The calculated survival rates at 3 years were 33%, 42%, and 68% for all patients, patients after complete resection, and patients with PCR, respectively.

CONCLUSION

This combined treatment modality is active in LAEC, with a PCR in 33% of the patients undergoing surgery. The results appear improved compared with those reported with surgery alone, by approximately doubling the 3-year survival rate. The high efficacy of preoperative chemoradiation warrants evaluation of the role of surgery in LAEC.
High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia. Results of protocol ALL VI from the Dutch Childhood Leukemia Study Group.
Authors: Veerman A J , Hählen K , Kamps W A , Van Leeuwen E F , De Vaan G A , Solbu G , Suciu S , Van Wering E R , Van der Does-Van der Berg A
Published: February 2017

PURPOSE

Here we report the results of a nationwide cooperative study in the Netherlands on acute lymphoblastic leukemia (ALL) in children. The aim of the study was to improve the cure rate and to minimize side effects in a group of non-high-risk ALL patients, especially with regard to the CNS. A second aim was to study potential prognostic factors.

METHODS

Children (age 0 to 15 years) with non-high-risk ALL (WBC count < 50 x 10(9)/L, no mediastinal mass, no B-cell phenotype, and no CNS involvement) were treated with a uniform protocol, ALL VI. The treatment protocol used 6-week induction regimen with three drugs (vincristine, dexamethasone, and asparaginase), three weekly doses of intravenous (IV) medium high-dose methotrexate (2 g/m2), and 2-year maintenance therapy that consisted of alternating 5-week periods of methotrexate and mercaptopurine and 2-week periods of vincristine and dexamethasone. In the first year of maintenance, triple intrathecal therapy was administered every 7 weeks.

RESULTS

From December 1, 1984 until July 1, 1988, 291 children with ALL were diagnosed; 206 were categorized as non-high-risk (71%), and 190 were treated according to protocol ALL VI. At 8 years, the event-free survival (EFS) rate was 81% (SE = 3%) and survival rate 85% (SE = 2.9%); the median follow-up time was 7.3 years (range, 36 to 117 months). The CNS relapse rate was 1.1% (two of 184 patients who achieved a complete remission [CR]). The only factor found to be of negative prognostic importance in terms of EFS (P = .05) was a positive acid phosphatase reaction.

CONCLUSION

For children with non-high-risk ALL, the combination of IV medium high-dose methotrexate (2 g/m2 times three), triple intrathecal therapy in the first year of maintenance treatment, and the use of dexamethasone for induction and pulses during maintenance treatment has proved to be highly effective, especially in the prevention of CNS relapse. A high cure rate was achieved without the use of anthracyclines, alkylating agents, and cranial irradiation.
Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen.
Authors: Magrath I , Adde M , Shad A , Venzon D , Seibel N , Gootenberg J , Neely J , Arndt C , Nieder M , Jaffe E , Wittes R A , Horak I D
Published: February 2017

PURPOSE

We have used identical treatment protocols for adults and children with small non-cleaved-cell lymphoma (SNCL) for many years and report here the results of two successive treatment regimens in these age groups.

PATIENTS AND METHODS

Seventy-two patients (39 adults and 33 children) were treated with protocol 77-04 between 1977 and 1985. All patients, except those with resected abdominal disease, received 15 cycles of a combination of cyclophosphamide (CTX), doxorubicin (ADR), prednisone (PRED), vincristine (VCR), high-dose methotrexate (MTX), and intrathecal (IT) therapy. Forty-one patients (20 adults and 21 children) were treated with protocol 89-C-41, which has been used since 1989. High-risk patients received four alternating cycles (with a total duration of 12 to 15 weeks) of an intensified version of protocol 77-04 without PRED (CODOX-M), and a new drug combination consisting of ifosfamide, etoposide, high-dose cytarabine (ara-C), and IT MTX (IVAC). Low-risk patients received three cycles of the CODOX-M regimen. High-risk patients were randomized to either receive or not receive granulocyte-macrophage colony-stimulating factor (GM-CSF).

RESULTS

Event-free survival (EFS) in protocol 77-04 was 56% at 2 years and beyond. EFS in protocol 89-C-41 was 92% at 2 years and beyond. GM-CSF was associated with increased thrombocytopenia.

CONCLUSION

Adults and children with SNCL have a similar prognosis when treated with the same chemotherapy. EFS in high-risk patients has been markedly improved by including IVAC in protocol 89-C-41, and excellent results can be achieved with only four cycles of therapy. In protocol 89-C-41, GM-CSF was not beneficial.
Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study.
Authors: Jeremic B , Shibamoto Y , Acimovic L , Milisavljevic S
Published: February 2017

PURPOSE

To investigate the efficacy of concurrent hyperfractionated radiation therapy (HFX RT) and low-dose daily chemotherapy (CHT) in stage III non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS

Between January 1990 and December 1991, 131 patients with histologically or cytologically confirmed stage III NSCLC, Karnofsky performance status (KPS) > or = 50, and no previous therapy were randomly treated as follows: group I, HFX RT with 1.2 Gy twice daily to a total dose of 69.6 Gy (n = 66); and group II, same HFX RT with CHT consisting of 50 mg of carboplatin (CBDCA) and 50 mg of etoposide (VP-16) given on each RT day (n = 65).

RESULTS

Group II patients had a significantly longer survival time than group I patients, with a median survival of 22 versus 14 months and 4-year survival rates of 23% versus 9% (P = .021). The median time to local recurrence and 4-year local recurrence-free survival rate were also significantly higher in group II than in group I (25 v 20 months and 42% v 19% respectively, P = .015). In contrast, the distant metastasis-free survival rate did not significantly differ in the two groups (P = .33). The two groups showed similar incidence of acute and late high-grade toxicity (P = .44 and .75, respectively). No treatment-related toxicity was observed.

CONCLUSION

The combination of HFX RT and low-dose daily CBDCA plus VP-16 was tolerable and improved the survival of patients with stage III NSCLC as a result of improved local control.
High-dose carboplatin, etoposide, and cyclophosphamide for patients with refractory germ cell tumors: treatment results and prognostic factors for survival and toxicity.
Authors: Motzer R J , Mazumdar M , Bosl G J , Bajorin D F , Amsterdam A , Vlamis V
Published: February 2017

PURPOSE

The efficacy and toxicity of high-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation (AuBMT) was investigated in a prospective trial for patients with cisplatin-refractory germ cell tumor (GCT). Prognostic factors for survival and treatment-related toxicity were identified.

PATIENTS AND METHODS

Fifty-eight patients with refractory GCT were treated with high-dose carboplatin, etoposide, and cyclophosphamide plus AuBMT. Prognostic factors for toxicity and survival were examined in multivariate analyses.

RESULTS

Twenty-three patients (40%) achieved a complete response and 12 (21%) are alive and free of disease at a median follow-up time of 28 months. Myelosuppression was severe and there were seven (12%) treatment-related deaths. Independently predictive factors that resulted in faster blood count recovery were the use of granulocyte colony-stimulating factor (G-CSF) for the number of days to neutrophil count recovery (P = .013) and prior treatment with cisplatin limited to six cycles or less for the number of days to platelet count recovery (P = .0012). Both were predictive for the number of days of hospitalization (P = .04 and .03, respectively). The two independently predictive variables for survival were pretreatment level of HCG; human chorionic gonadotrophin (HCG; < or = 100 times the upper limit of normal [xnl] v > 100 xnl, P = .02) and the presence of retroperitoneal metastases (yes or no, P = .04). Patients grouped by HCG < or = 100 xnl with retroperitoneal metastases, HCG < or = 100 xnl without retroperitoneal metastases, and all patients with HCG more than 100 xnl had median survival times of 14, 11, and 3 months, respectively (P = .04).

CONCLUSION

High-dose carboplatin, etoposide, and cyclophosphamide is an effective therapy for patients with refractory GCT, and results in a complete response proportion of 40% and a 2-year survival rate of 31% at a median follow-up time of 28 months. This was accomplished in a group of patients with a dismal prognosis to conventional-dose therapy.