bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchronous and Metachronous Squamous Cell Carcinomas of the Head and Neck Mucosal Sites
Authors: Erkal Haldun Ş. , Mendenhall William M. , Amdur Robert J. , Villaret Douglas B. , Stringer Scott P.
Published: February 2017

PURPOSE: The present study presents the experience at the University of Florida with synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites.

PATIENTS AND METHODS: This study included 1,112 patients with squamous cell carcinomas of the oropharynx, hypopharynx, and supraglottic larynx treated with radiation therapy with curative intent from 1964 to 1997. All patients had follow-up for at least 2 years. No patients were lost to follow-up.

RESULTS: The overall survival rate was 45% and the disease-specific survival rate was 67% at 5 years after initial diagnosis of carcinoma of the head and neck mucosal sites. Seventy-seven patients (7%) presented with synchronous carcinomas of the head and neck mucosal sites and 103 patients (9%) developed metachronous carcinomas of the head and neck mucosal sites at 0.6 to 21.7 years (median, 3.6 years). The overall survival rate was 31%, and the disease-specific survival rate was 50% at 5 years after metachronous carcinomas of the head and neck mucosal sites. Seven patients (1%) developed metachronous carcinomas of the thoracic esophagus at 1 to 11.1 years (median, 2.8 years), 15 patients (1%) presented with synchronous carcinomas of the lung, and 83 patients (7%) developed metachronous carcinomas of the lung at 0.6 to 17.6 years (median, 3.5 years).

CONCLUSION: Development of synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites are in part responsible for failure to improve overall survival rates for patients with squamous cell carcinomas of the head and neck mucosal sites, justifying rigorous follow-up and studies on chemoprevention.
Reproductive Factors and Risk of Intermediate- or High-Grade B-Cell Non-Hodgkin’s Lymphoma in Women
Authors: Nelson Rebecca A. , Levine Alexandra M. , Bernstein Leslie
Published: February 2017

PURPOSE: The incidence rates of non-Hodgkin’s lymphoma (NHL) unrelated to human immunodeficiency virus infection are lower for women than for men; yet, few factors have been identified that may account for this difference in risk. NHL is difficult to study epidemiologically because this disorder represents a group of malignancies that differ in terms of morphologic presentation, immunologic features, genetic characteristics, prognosis, and etiology.

PATIENTS AND METHODS: We conducted a population-based case-control study in women to determine whether reproductive factors or hormonal exposures might be related to the risk of high- or intermediate-grade B-cell NHL. We interviewed 177 female residents of Los Angeles County who were diagnosed with high- or intermediate-grade B-cell NHL between 1989 and 1992; each case patient was individually matched on age and race to a control subject who lived in her neighborhood.

RESULTS: Women who had used oral contraceptives had significantly lower risk of intermediate- or high-grade NHL (multivariate odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.26 to 0.86) than women who had never used these compounds. Among parous women, those who had used lactation suppressants (which contain high levels of estrogen) had significantly lower risk of NHL (multivariate OR = 0.50; 95% CI, 0.29 to 0.85) than unexposed women. Postmenopausal women had a somewhat greater risk of NHL than premenopausal women, whereas those postmenopausal women who had used hormone replacement therapy (HRT) (primarily estrogen) had somewhat lower risk than those who had not used HRT.

CONCLUSION: Exogenous estrogens seem to have a protective effect on the risk of high- and intermediate-grade B-cell NHL. Although the mechanisms for such protection are not known, alterations in immune reactivity, cytokine expression, or B-cell modulation may play a role.
Autologous Stem-Cell Transplantation for Hodgkin’s Disease: Results and Prognostic Factors in 494 Patients From the Grupo Español de Linfomas/Transplante Autólogo de Médula Ósea Spanish Cooperative Group
Authors: Sureda A. , Arranz R. , Iriondo A. , Carreras E. , Lahuerta J.J. , García-Conde J. , Jarque I. , Caballero M.D. , Ferrà C. , López A. , García-Laraña J. , Cabrera R. , Carrera D. , Ruiz-Romero M.D. , León A. , Rifón J. , Díaz-Mediavilla J. , Mataix R. , Morey M. , Moraleda J.M. , Altés A. , López-Guillermo A. , de la Serna J. , Fernández-Rañada J.M. , Sierra J. , Conde E.
Published: February 2017

PURPOSE: To analyze clinical outcome and significant prognostic factors for overall (OS) and time to treatment failure (TTF) in a group of 494 patients with Hodgkin’s disease (HD) undergoing autologous stem-cell transplantation (ASCT).

PATIENTS AND METHODS: Detailed records from the Grupo Español de Linfomas/Transplante Autólogo de Médula Ósea Spanish Cooperative Group Database on 494 HD patients who received an ASCT between January 1984 and May 1998 were reviewed. Two hundred ninety-eight males and 196 females with a median age of 27 years (range, 1 to 63 years) received autografts while in complete remission (n = 203) or when they had sensitive disease (n = 206) or resistant disease (n = 75) at a median time of 26 months (range, 4 to 259 months) after diagnosis. Most patients received high-dose chemotherapy without radiation for conditioning (n = 443). The graft consisted of bone marrow (n = 244) or peripheral blood (n = 250).

RESULTS: The 100-day mortality rate was 9%. The 5-year actuarial TTF and OS rates were 45.0% (95% confidence interval [CI], 39.5% to 50.5%) and 54.5% (95% CI, 48.4% to 60.6%), respectively. In multivariate analysis, the presence of active disease at transplantation, transplantation before 1992, and two or more lines of therapy before transplantation were adverse prognostic factors for outcome. Sixteen patients developed a secondary malignancy (5-year cumulative incidence of 4.3%) after transplantation. Adjuvant radiotherapy before transplantation, the use of total-body irradiation (TBI) in the conditioning regimen, and age ≥ 40 years were found to be predictive factors for the development of second cancers after ASCT.

CONCLUSION: ASCT achieves long-term disease-free survival in HD patients. Disease status before ASCT is the most important prognostic factor for final outcome; thus, transplantation should be considered in early stages of the disease. TBI must be avoided in the conditioning regimen because of a significantly higher rate of late complications, including secondary malignancies.
Mutations With Loss of Heterozygosity of p53 Are Common in Therapy-Related Myelodysplasia and Acute Myeloid Leukemia After Exposure to Alkylating Agents and Significantly Associated With Deletion or Loss of 5q, a Complex Karyotype, and a Poor Prognosis
Authors: Christiansen Debes H. , Andersen Mette K. , Pedersen-Bjergaard Jens
Published: February 2017

PURPOSE: To study mutations and loss of heterozygosity (LOH) of p53 in therapy-related myelodysplasia (t-MDS) and acute myeloid leukemia (t-AML).

PATIENTS AND METHODS: Fifty-two unselected patients with t-MDS and 25 patients with t-AML were studied by polymerase chain reaction (PCR)–single-strand conformational polymorphism (SSCP) at the DNA level and by reverse transcriptase (RT)-PCR–SSCP at the mRNA level, and cases with aberrant SSCP patterns were sequenced.

RESULTS: Somatically acquired mutations of p53 were observed in 21 of 77 cases of t-MDS or t-AML, and 19 of these 21 patients had received alkylating agents. Single-base substitutions at A:T pairs were more common in t-MDS and t-AML, whereas single-base substitutions at G:C pairs are most common in MDS and AML de novo and in solid tumors. Six patients demonstrated a cytogenetic loss of 17p13, and these six and an additional nine patients with p53 mutations demonstrated LOH of p53 at the DNA or mRNA level. This suggests a cytogenetic loss of the normal p53 allele in these nine cases combined with duplication of the homologous chromosome 17 carrying the mutated p53 allele. Mutations of p53 were significantly associated with deletion or loss of 5q (P < .0001) and a complex karyotype (P = .0001), but surprisingly were not associated with deletion or loss of 7q (P = .73), and were infrequent in patients with balanced chromosome translocations (P = .03). Mutations of p53 were more common in older patients (P = .036) and were associated with an extremely poor prognosis (P = .014), apparently restricted to the 15 cases with LOH of p53 ( P = .046).

CONCLUSION: Mutations with loss of function of p53 are significantly associated with deletion or loss of 5q in t-MDS and t-AML after previous treatment with alkylating agents and are associated with genetic instability.
Results of the Fludarabine and Cyclophosphamide Combination Regimen in Chronic Lymphocytic Leukemia
Authors: O’Brien Susan M. , Kantarjian Hagop M. , Cortes Jorge , Beran Miloslav , Koller Charles A. , Giles Francis J. , Lerner Susan , Keating Michael
Published: February 2017

PURPOSE: To assess the efficacy of combination therapy with fludarabine and cyclophosphamide in patients with chronic lymphocytic leukemia (CLL) based on data suggesting in vitro synergistic activity of the two agents.

PATIENTS AND METHODS: A total of 128 patients with CLL were treated with fludarabine 30 mg/m2 intravenously daily for 3 days and cyclophosphamide at either 500 mg/m2 daily for 3 days (n = 11), 350 mg/m2/d for 3 days (n = 26), or 300 mg/m2 daily for 3 days (n = 91). The cyclophosphamide dose was decreased because of myelosuppression in the early part of the study. Patients were divided into four groups based on the expectation for response to single-agent fludarabine, including previously untreated patients, patients previously treated with alkylating agents, patients successfully treated with alkylating agents and fludarabine but relapsing, and patients refractory to fludarabine with or without alkylating agents.

RESULTS: Fludarabine and cyclophosphamide produced ≥ 80% response rates in all patients not refractory to fludarabine at the start of therapy as well as a 38% response rate in patients who were refractory to fludarabine. The complete remission (CR) rate was 35% in previously untreated patients, which was not significantly different from the CR rate in historical control patients treated with single-agent fludarabine. However, residual disease assessed by flow cytometry occurred in only 8% of previously untreated patients achieving CR, and median time to progression has not been reached after a median follow-up of 41 months. The main complication of therapy was related to myelosuppression and infection. Neutropenia to less than 500 × 109/L was noted in 48% of patients who received cyclophosphamide 300 mg/m2. Pneumonia or sepsis occurred in 25% of patients, and fever of unknown origin occurred in another 25%. Pneumonia or sepsis were significantly more frequent in patients who were refractory to fludarabine at the start of combination chemotherapy.

CONCLUSION: Fludarabine and cyclophosphamide seem to have a significant advantage over single-agent fludarabine in the salvage setting. Although the CR rate was not increased in previously untreated patients, residual disease detected by flow cytometry was rare and remission durations seemed to be prolonged in this subset. Myelosuppression and infection remain the most significant complications of therapy in CLL.
High-Dose Interferon Alfa-2b Does Not Diminish Antibody Response to GM2 Vaccination in Patients With Resected Melanoma: Results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696
Authors: Kirkwood John M. , Ibrahim Joseph , Lawson David H. , Atkins Michael B. , Agarwala Sanjiv S. , Collins Keirsten , Mascari Ruth , Morrissey Donna M. , Chapman Paul B.
Published: February 2017

PURPOSE: High-dose interferon alfa-2b (IFNα2b) is the only established adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a chemically defined vaccine that is one of the best developed of a range of vaccine candidates for melanoma. A single-institution phase III trial conducted at Memorial Hospital served as the impetus for an intergroup adjuvant E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients. To build on the apparent benefit of IFNα2b in resectable high-risk American Joint Committee on Cancer (AJCC) stage IIB or III melanoma, this phase II study was designed to evaluate the combination of GMK and IFNα2b. The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFNα2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies.

PATIENTS AND METHODS: This trial enrolled 107 patients with resectable high- or very high–risk melanoma (AJCC stages IIB, III, and IV).

RESULTS: The results demonstrate that IFNα2b does not significantly inhibit immunoglobulin M or G serologic responses to the vaccine and that the combination of high-dose IFNα2b and GMK is well tolerated in this patient population.

CONCLUSION: Cox analysis of the results of the combination with IFNα2b show improvement in the relapse-free survival of patients with very high–risk melanoma (including those with resectable M1 disease).
Patterns of Use of Chemotherapy for Breast Cancer in Older Women: Findings From Medicare Claims Data
Authors: Du Xianglin , Goodwin James S.
Published: February 2017

PURPOSE: There is little population-based information available on the use of chemotherapy in women with breast cancer. This study describes the use of chemotherapy through analysis of Medicare claims and determines the correlates of chemotherapy use.

PATIENTS AND METHODS: We used the merged Surveillance, Epidemiology, and End Results–Medicare database and identified women ≥ 65 years of age diagnosed with breast cancer in 1991 and 1992. Chemotherapy was ascertained from Medicare claims through procedure codes for chemotherapy made within 24 months of the diagnosis.

RESULTS: In women with stages I, II, III, and IV breast cancer, the percentage receiving chemotherapy within 24 months of diagnosis was 5.1%, 19.5%, 33.9%, and 35.2%, respectively. Most women receiving chemotherapy had two to 12 claims; the median number was eight. Use of chemotherapy decreased significantly with age across all tumor stages; eg, in women with stage III cancer, the use of chemotherapy declined from 49% in those aged 65 to 69 years to 10% in those ≥ 80 years old. In a multivariate analysis, there was little variation by ethnicity. Chemotherapy use was highest (70%) in women aged 65 to 69 years with node-positive and estrogen receptor–negative tumors and lowest (5%) in those with node-negative and estrogen receptor–positive tumors. Compared with those without comorbid diseases, patients with a comorbidity score of 2 had significantly lower use of chemotherapy.

CONCLUSION: Medicare claims data seem to provide valuable information on the use of chemotherapy for breast cancer in older women. However, external validation of the accuracy and completeness of these data is required before any firm conclusion can be drawn.
Nipple Fluid Carcinoembryonic Antigen and Prostate-Specific Antigen in Cancer-Bearing and Tumor-Free Breasts
Authors: Zhao Yashuang , Verselis Sigitas J. , Klar Neil , Sadowsky Norman L. , Kaelin Carolyn M. , Smith Barbara , Foretova Lenka , Li Frederick P.
Published: February 2017

PURPOSE: Mammograms and breast examinations are established methods for early breast cancer detection. Routine mammography screening reduces breast cancer mortality among women ages ≥ 50 years, but additional screening methods are needed. We and others have found high levels of carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) in nipple aspirate fluids (NAFs), but the usefulness for these bio-markers for early breast cancer detection is unknown.

PATIENTS AND METHODS: NAFs from one or both breasts of 388 women were analyzed for CEA, PSA, and albumin levels. The study included 44 women with newly diagnosed invasive breast cancers, 67 women with proliferative breast lesions (ductal and lobular carcinoma in situ and atypical ductal hyperplasia), and 277 controls without these breast lesions. Analyses were conducted using the log10-transformed CEA and PSA levels to normalize the distributions of these tumor markers.

RESULTS: Nipple fluid CEAs are significantly higher for cancerous breasts than tumor-free breasts (median 1,830 and 1,400 ng/mL, respectively; P < .01). However, at 90% specificity of the assay (CEA = 11,750 ng/mL), the corresponding sensitivity for cancer detection is 32%. CEA levels are not significantly different for breasts with proliferative lesions compared with tumor-free breasts. Nipple fluid PSAs do not differ by tumor status. Analyses of NAF albumin-standardized CEAs and PSAs yield similar results. Nipple fluid CEA and PSA titers are correlated in the affected and unaffected breast of women with unilateral lesions.

CONCLUSION: Nipple fluid CEAs are higher for breasts with untreated invasive cancers, but the test sensitivity is low. Nipple fluid PSA titers do not seem to be useful for breast cancer detection.
Phase I and Pharmacokinetic Study of Exatecan Mesylate (DX-8951f): A Novel Camptothecin Analog
Authors: Royce Melanie E. , Hoff Paulo M. , Dumas Pamela , Lassere Yvonne , Lee J. Jack , Coyle John , Ducharme Murray P. , De Jager Robert , Pazdur Richard
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic (PK) profile, and recommended phase II dose of Exatecan mesylate (DX-8951f) when administered as a 24-hour continuous infusion every 3 weeks to patients with solid tumors.

PATIENTS AND METHODS: Twenty-two patients with advanced solid tumors, all previously treated, and with performance status ≤ 2, were entered. The starting dose of DX-8951f was 0.15 mg/m2; the dose was escalated according to the modified continual reassessment method. The drug was administered until disease progression or until unacceptable toxic effects occurred.

RESULTS: Seven dose escalations were completed, and a total of 53 courses were delivered (median, two courses; range, one to eight courses) during the study. At doses 1.2 mg/m2 and lower, toxicities were mostly grade 1, primarily hematologic. In the initial cohort of three patients treated at 2.4 mg/m2, grade 2 hematologic toxicity was observed. Of the six additional patients entered at 2.4 mg/m2, three had grade 3 or 4 granulocytopenia. At doses higher than 2.4 mg/m2, DLT granulocytopenia was observed. Nonhematologic toxicities, including nausea, vomiting, diarrhea, fatigue, and alopecia, were mild to moderate. Neither complete nor partial responses were observed, but four patients had stable disease. The PK profile of DX-8951f seemed linear at the doses administered. The plasma clearance, total volume of distribution, and terminal elimination half-life were approximately 3 L/h, 40 L, and 14 hours, respectively.

CONCLUSION: The DLT of this DX-8951f schedule was granulocytopenia for minimally pretreated patients, and both granulocytopenia and thrombocytopenia for heavily pretreated patients. The MTD for both minimally and heavily pretreated patients was 2.4 mg/m2. DX-8951f seems to have a linear PK profile on the basis of single-dose administration. The recommended phase II dose with this schedule is 2.4 mg/m2 for minimally pretreated patients. A lower dose should be used for heavily pretreated patients.
Phase I/II Study of the P-Glycoprotein Modulator PSC 833 in Patients With Acute Myeloid Leukemia
Authors: Dorr R. , Karanes C. , Spier C. , Grogan T. , Greer J. , Moore J. , Weinberger B. , Schiller G. , Pearce T. , Litchman M. , Dalton W. , Roe D. , List A. F.
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose, pharmacokinetic interaction, and activity of PSC 833 compared with daunorubicin (DNR) and cytarabine in patients with poor-risk acute myeloid leukemia.

PATIENTS AND METHODS: Patients received ara-C 3 g/m2/d on 5 consecutive days, followed by an IV loading dose of PSC 833 (1.5 mg/kg) and an 84-hour continuous infusion escalating from 6, 9, or 10 mg/kg/d. Daunorubicin was administered as a 72-hour continuous infusion at 34 or 45 mg/kg/d. Responding patients received consolidation chemotherapy with DNR pharmacokinetics performed without PSC-833 on day 1, and with PSC-833 on day 4. Response was correlated with expression of P-glycoprotein and lung resistance protein (LRP), and in vitro sensitization of leukemia progenitors to DNR cytotoxicity by PSC 833.

RESULTS: All 43 patients are assessable for toxicity and response. Grade 3 or greater hyperbilirubinemia (70%) was the only dose-dependent toxicity. Four patients (9%) succumbed to treatment-related complications. Twenty-one patients (49%) achieved a complete remission or restored chronic phase, including 10 of 20 patients treated at the maximum-tolerated dose of 10 mg/kg/d of PSC-833 and 45 mg/m2 of DNR. The 95% confidence interval for complete response was 33.9% to 63.7%. Administration of PSC 833 did not alter the mean area under the curve for DNR, although clearance decreased approximately two-fold (P = .04). Daunorubicinol clearance decreased 3.3-fold (P = .016). Remission rates were not effected by mdr-1 expression, but LRP overexpression was associated with chemotherapy resistance.

CONCLUSION: Combined treatment with infused PSC 833 and DNR is well tolerated and has activity in patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays elimination of daunorubicinol, but yields variable changes in DNR systemic exposure.
Second-Line Chemotherapy in Patients With Relapsed Extragonadal Nonseminomatous Germ Cell Tumors: Results of an International Multicenter Analysis
Authors: Hartmann Jörg T. , Einhorn Lawrence , Nichols Craig R. , Droz Jean-P. , Horwich Alan , Gerl Arthur , Fossa Sophie D. , Beyer Jörg , Pont Jörg , Schmoll Hans-J. , Kanz Lothar , Bokemeyer Carsten
Published: February 2017

PURPOSE: Relapsed extragonadal germ cell tumors patients (EGGCT) are treated with identical salvage chemotherapy regimens, as are patients with metastatic testicular cancer. This investigation evaluates the results of second-line chemotherapy in nonseminomatous EGGCT and tries to identify prognostic factors for survival.

PATIENTS AND METHODS: We conducted a retrospective review of 142 patients treated at eleven European and American centers between 1975 and 1996. All had received cisplatin-containing regimens as induction treatment.

RESULTS: Twenty-seven of 142 patients (19%) were long-term disease-free, 11% with primary mediastinal and 30% of patients with primary retroperitoneal disease. Median follow-up since start of salvage treatment was 11 months (range, 1 to 157) for all patients and 45 months (range, 6 to 157) for surviving patients. Forty-eight patients (34%) received high dose chemotherapy with autologous bone marrow transplant at relapse, and 10 of these patients (21%) are continuously disease-free. Primary mediastinal location (P = .003), sensitivity to cisplatin (P = .003), elevated β-HCG at relapse (P = .04), and normal LDH at diagnosis (P = .01) were shown to be significant negative prognostic factors for overall survival in univariate; mediastinal location [relative risk ratios (HR) = 1.9; 95% confidence intervals (CI), 1.2 to 3.0] and sensitivity to cisplatin [HR = 2.4; 95% CI, 1.1 to 5.2] were significant negative prognostic factors in multivariate analysis.

CONCLUSION: Although current salvage strategies will cure between 20% and 50% of recurrent metastatic testicular cancer, relapsed nonseminomatous EGGCT patients appear to have an inferior survival rate, in particular in case of primary mediastinal location. Mediastinal primary tumor and inadequate response to cisplatin-based induction chemotherapy have been identified as independent negative prognostic factors, both associated with an approximately two-fold higher risk for failure of salvage treatment.
Recommendations for Cancer Prevention Trials Using Potentially Ototoxic Test Agents
Authors: Shotland Lawrence I. , Ondrey Frank G. , Mayo Kristen A. , Viner Jaye L.
Published: February 2017

PURPOSE: Preventive oncology applies pharmacologic agents to reverse, retard, or halt progression of neoplastic cells to invasive malignancy, a process that may require administration of agents over long periods of time. Although ototoxicity may be a tolerable side effect of anticancer or antimicrobial therapy, even modest ototoxicity may not be acceptable in agents developed for preventive oncology that are routinely administered to subjects who neither are, nor necessarily will become, clinically ill.

MATERIALS AND METHODS: Age-related shifts in hearing may occur over the course of longterm or open-ended therapy; consequently, age-adjusted norms enable researchers to better distinguish hearing loss caused by drugs from that caused by aging. Norms for hearing sensitivity are derived from the Baltimore Longitudinal Study of Aging and are the basis for the proposed audiologic monitoring recommendations.

RESULTS: Audiologic monitoring recommendations are presented that standardize patient selection, adverse event reporting, posttreatment follow-up, and audiologic testing for potentially ototoxic investigational agents.

CONCLUSION: These recommendations are applicable to trials of investigational agents as well as various classes of drugs used in routine clinical care.
Decision Support for Patients With Early-Stage Breast Cancer: Effects of an Interactive Breast Cancer CDROM on Treatment Decision, Satisfaction, and Quality of Life
Authors: Molenaar Sjaak , Sprangers Mirjam AG , Rutgers Emiel J. Th. , Luiten Ernest JT , Mulder Jan , Bossuyt Patrick MM , van Everdingen Jannes JE , Oosterveld Paul , de Haes Hanneke CJM
Published: February 2017

PURPOSE: To investigate the effects of the Interactive Breast Cancer CDROM as a decision aid for breast cancer patients with a choice between breast conserving therapy (BCT) and mastectomy (MT).

PATIENTS AND METHODS: Consecutive patients with stage I and II breast cancer were enrolled. A quasi-experimental, longitudinal, and pretest/posttest design was used. Follow-up was scheduled 3 and 9 months after discharge from the hospital. Control patients (n = 88) received standard care (oral information and brochures). The CDROM was provided to patients in the experimental condition (n = 92) as a supplement to standard procedures. Outcome variables were treatment decision, satisfaction, and quality of life (QoL).

RESULTS: No effect on treatment decision was found. CDROM patients expressed more general satisfaction with information at 3 and 9 months (95% confidence interval for the difference (d) between the means (d: 4.1 to 12.5 and 5.7 to 14.2 respectively). CDROM patients were also more satisfied with their treatment decision at 3 and at 9 months (d: 0.1 to 0.4; 0.2 to 0.5). Moreover, at 9 months, CDROM patients were more satisfied with breast cancer–specific information (d: 0.9 to 16.5), the decision-making process (d: 0.1 to 0.4), and communication (d: 0.2 to 11.0). At 3 and 9 months, a positive effect was found on general health (d: 0.2 to 14.5 and 0.3 to 15.0). Moreover, at 9 months, CDROM patients reported better physical functioning (d: 5.1 to 19.8), less pain (d: -17.9 to -4.5), and fewer arm symptoms (d: -14.1 to -0.5).

CONCLUSION: The Interactive Breast Cancer CDROM improved decision making in patients with early-stage breast cancer with a choice between BCT and MT, as evaluated in terms of patients’ satisfaction and QoL.
Discussing Adjuvant Cancer Therapy
Authors: Leighl Natasha , Gattellari Melina , Butow Phyllis , Brown Richard , Tattersall Martin H.N.
Published: February 2017

PURPOSE: To document the adequacy of patient information in oncology consultations concerning adjuvant therapy and explore predictors of physician communication patterns, treatment decisions, patient information recall, and satisfaction.

PATIENTS AND METHODS: Retrospective analysis of audiotapes and verbatim transcripts of 101 initial adjuvant therapy consultations with medical and radiation oncologists was undertaken. Content analysis, data on communication patterns, treatment decisions, patient anxiety, satisfaction, and information recall were collected. Predictors of physician communication, treatment decisions, recall, and satisfaction with the consultation were identified.

RESULTS: The majority of patients were well informed of their prognosis, benefits and risks of therapy, and alternative management options. Only half were asked about preferences for information or decision-making involvement. Predictors of information detail given include patient sex, age, occupation, and education. Radiation and medical oncologists express prognosis and treatment benefit using similar phrases. When offered the chance to delay decision-making, most patients do so (P < .01). Final treatment decisions appear to be influenced by the presentation of choice in treatment options by the oncologist and whether the treatment decision was made during the initial consultation (P < .01). Information recall was not influenced by communication factors. Patients receiving less detailed information had slightly higher satisfaction with the consultation (P = .03). More anxious patients tended to be less satisfied (P = .07).

CONCLUSION: The optimal way to discuss adjuvant therapy is undefined. More emphasis can be placed on soliciting patient preferences for information and decision-making involvement and tailoring both to the needs of the individual patient. Providing choice in treatment and delaying decision-making may affect the patient’s treatment decision.
Circulating Neuroblastoma Cells Detected by Reverse Transcriptase Polymerase Chain Reaction for Tyrosine Hydroxylase mRNA Are an Independent Poor Prognostic Indicator in Stage 4 Neuroblastoma in Children Over 1 Year
Authors: Burchill Susan A. , Lewis Ian J. , Abrams Keith R. , Riley Richard , Imeson John , Pearson Andrew D.J. , Pinkerton Ross , Selby Peter
Published: February 2017

PURPOSE: In this prospective, multicenter study, the independent prognostic power of neuroblastoma cells detected by reverse transcriptase polymerase chain reaction (RT-PCR) for tyrosine hydroxylase (TH) mRNA was evaluated.

PATIENTS AND METHODS: The clinical significance of disease detected by RT-PCR in peripheral blood from children at diagnosis was compared with established prognostic markers [ie, age, lactate dehydrogenase (LDH), neuron-specific enolase, ferritin, and MYCN gene amplification] by multivariate analysis. The value of disease detection by RT-PCR during treatment and follow-up was also examined.

RESULTS: TH mRNA was detected in peripheral blood from 33 of 49 (67%) children with stage 4 neuroblastoma > 1 year old at diagnosis and was a significant predictive factor for overall survival [hazard ratio (HR) = 2.40, 95% confidence interval (CI) 1.19 to 4.84, P = .014) and event-free survival (HR = 2.09, 95% CI 1.06 to 4.17, P = .034) in a multivariate analysis. Detection of disease in blood from clinically disease-free children was related to increased risk of death (HR 2.54, 95% CI 1.42 to 4.55, P = .0014).

CONCLUSION: TH mRNA in peripheral blood of children with neuroblastoma is a poor prognostic indictor, reflecting the propensity for dissemination via the bloodstream. When combined with a serum LDH > 1500 IU/L, this is the most powerful poor prognostic model at diagnosis for children > 1 year old with stage 4 disease. The detection of TH mRNA in peripheral blood from clinically disease-free children is related to increased risk of relapse and death.
Immediate Neurocognitive Effects of Methylphenidate on Learning-Impaired Survivors of Childhood Cancer
Authors: Thompson Stephen J. , Leigh Laurie , Christensen Robbin , Xiong Xiaoping , Kun Larry E. , Heideman Richard L. , Reddick W. Eugene , Gajjar Amar , Merchant Thomas , Pui Ching-Hon , Hudson Melissa M. , Mulhern Raymond K.
Published: February 2017

PURPOSE: To test if methylphenidate (MPH) has an objective beneficial effect on immediate performance on tests of neurocognitive functions among learning-impaired survivors of childhood acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT).

PATIENTS AND METHODS: From July 1, 1997 through December 31, 1998, 104 long-term survivors of childhood ALL or a malignant BT completed neurocognitive screening for learning impairments and concurrent problems with sustained attention. Eligibility criteria for the MPH trial included an estimated intelligence quotient greater than 50, academic achievement in the 16th percentile or lower for age in reading, math, or spelling, and an ability to sustain attention on a computerized version of the Conners’ Continuous Performance Test (CPT) in the 16th percentile or lower for age and sex. Of the 104, 32 (BT, n = 25; ALL, n = 7) were eligible on the basis of these a priori criteria for a randomized, double-blinded, placebo-controlled trial of MPH. The patients ingested a placebo (lactose) or MPH (0.6 mg/kg; 20 mg maximum) and repeated selected portions of the screening battery 90 minutes later.

RESULTS: Compared to the 17 patients randomized to the placebo group, the 15 patients randomized to the MPH group had a significantly greater improvement on the CPT for sustained attention (errors of omission, P = .015) and overall index (P = .008) but not for errors of commission (indicative of impulsiveness) nor reaction times. A trend for greater improvement in the MPH group on a measure of verbal memory failed to reach statistical significance. No trend was observed for MPH effectiveness in improving learning of a word association task. No significant side effects from MPH were observed.

CONCLUSION: MPH resulted in a statistically significant improvement on measures of attention abilities that cannot be explained by placebo or practice effects.
Phase I Trial of Oral Green Tea Extract in Adult Patients With Solid Tumors
Authors: Pisters Katherine M.W. , Newman Robert A. , Coldman Brenda , Shin Dong M. , Khuri Fadlo R. , Hong Waun Ki , Glisson Bonnie S. , Lee Jin S.
Published: February 2017

PURPOSE: This trial was designed to determine the maximum-tolerated dose, toxicity, and pharmacology of oral green tea extract (GTE) once daily or three times daily.

PATIENTS AND METHODS: Cohorts of three or more adult cancer patients were administered oral GTE with water after meals one or three times daily for 4 weeks, to a maximum of 6 months, depending on disease response and patient tolerance. Pharmacokinetic analyses were encouraged but optional.

RESULTS: Dose levels of 0.5 to 5.05 g/m2 qd and 1.0 to 2.2 g/m2 tid were explored. A total of 49 patients were studied. Patient characteristics: median age, 57 years (range, 27 to 77 years); 23 patients were women (47%); 98% had a Zubrod PS of 1%; 98% had PS of 1; and 21 had non–small-cell lung, 19 had head & neck cancer, three had mesothelioma, and six had other. Mild to moderate toxicities were seen at most dose levels and promptly reversed on discontinuation of GTE. Dose-limiting toxicities were caffeine related and included neurologic and gastrointestinal effects. The maximum-tolerated dose was 4.2 g/m2 once daily or 1.0 g/m2 three times daily. No major responses occurred; 10 patients with stable disease completed 6 months of GTE. Pharmacokinetic analyses found accumulation of caffeine levels that were dose dependent, whereas epigallocatechin gallate levels did not accumulate nor appear dose related.

CONCLUSION: A dose of 1.0 g/m2 tid (equivalent to 7 to 8 Japanese cups [120 mL] of green tea three times daily) is recommended for future studies. The side effects of this preparation of GTE were caffeine related. Oral GTE at the doses studied can be taken safely for at least 6 months.
No Downstaging After Short-Term Preoperative Radiotherapy in Rectal Cancer Patients
Authors: Marijnen C.A.M. , Nagtegaal I.D. , Kranenbarg E. Klein , Hermans J. , van de Velde C.J.H. , Leer J.W.H. , van Krieken J.H.J.M. ,   for the Pathology Review Committee and the Cooperative Clinical Investigators
Published: February 2017

PURPOSE: In retrospective studies, total mesorectal excision (TME) surgery has been demonstrated to result in a reduction in the number of local recurrences of rectal cancer. Reports on improved local control after preoperative, hypofractionated radiotherapy have led to the introduction of a randomized multicenter trial to evaluate the effect of TME surgery with and without preoperative radiotherapy. Treatment with preoperative radiotherapy might have an effect on the pathologic characteristics that determine staging of rectal cancer. We investigated the occurrence of downstaging in rectal cancer patients treated with and without preoperative radiotherapy.

PATIENTS AND METHODS: We analyzed the differences in tumor size, number of examined lymph nodes, tumor-node-metastasis stage, and histopathologic features in 1,321 patients entered onto a randomized trial. The trial compared preoperative radiotherapy (5 × 5 Gy) followed by TME surgery with TME surgery alone. Patients who had an interval of more than 10 days between the start of radiotherapy and surgery were excluded from analysis.

RESULTS: Differences were observed in tumor size (P < .001) and total number of examined lymph nodes (P < .001). No difference in tumor or node classification was detected. The irradiated group demonstrated more poorly differentiated tumors as well as more mucinous tumors.

CONCLUSION: In rectal cancer patients, short-term, preoperative radiotherapy with 5 × 5 Gy does not lead to downstaging if the interval between the start of radiotherapy and surgery does not exceed 10 days.
Phase II Study of the Cyclin-Dependent Kinase Inhibitor Flavopiridol Administered to Patients With Advanced Gastric Carcinoma
Authors: Schwartz Gary K. , Ilson David , Saltz Leonard , O’Reilly Eileen , Tong William , Maslak Peter , Werner Jeanine , Perkins Pam , Stoltz Maxine , Kelsen David
Published: February 2017

PURPOSE: Flavopiridol is the first cyclin-dependent kinase inhibitor to enter clinical trials. Activity in gastric cancer xenografts and in a patient with gastric cancer on the phase I trial led to this phase II study of flavopiridol in patients with metastatic gastric cancer.

PATIENTS AND METHODS: Sixteen patients were entered onto the study, and 14 were assessable for response. Flavopiridol was administered initially at a dose of 50 mg/m2/d by continuous infusion for 72 hours every 2 weeks. Assessment of plasma pharmacokinetics was performed in all patients. Peripheral mononuclear cells were collected throughout the 72-hour infusion for determinants of apoptosis.

RESULTS: There were no major objective responses (exact confidence interval 0% to 23%). One patient achieved a minor response in his liver metastases, though the primary progressed. Other patients exhibited histologic and radiographic evidence of tumor necrosis. Common toxicities included fatigue in 93% of patients (grade 3 or 4 in 27%) and diarrhea in 73% of patients (grade 3 or 4 in 20%). Five patients (33%) developed venous thromboses at the central catheter tip. The studies performed on peripheral mononuclear cells indicated no induction of apoptosis.

CONCLUSION: Flavopiridol administered as a single agent for 72 hours every 14 days is inactive in the treatment of gastric cancer. The drug also induced an unexpected higher incidence of vascular thrombosis and fatigue than was anticipated from the phase I trials. Future development of flavopiridolwill depend on other doses and schedules in combination with chemotherapy.
Self-Reported Quality of Life of Individual Cancer Patients: Concordance of Results With Disease Course and Medical Records
Authors: Velikova Galina , Wright Penny , Smith Adam B. , Stark Daniel , Perren Timothy , Brown Julia , Selby Peter
Published: February 2017

PURPOSE: To investigate the applicability of a standard quality of life (QL) questionnaire to individual cancer patients and to explore the potential for impact of QL information on the process of care by comparing at group level the QL results with the medical records.

PATIENTS AND METHODS: One hundred fourteen consecutive patients at the oncology clinics at St James’s Hospital, Leeds, United Kingdom, completed the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 on a touch-screen computer over a 6-month period. The QL results were compared with the corresponding medical records at individual and group level.

RESULTS: For individual patients, the serial measurement of QL allowed recognition of patterns over time corresponding to disease course. At group level, a higher proportion of patients reported problems on EORTC QLQ-C30 than were mentioned in the medical records (McNemar paired test, P < .01). Most often clinicians mentioned pain (22% to 39%), and at the initial visit role (66%), and social issues (77%). For the rest of the symptoms and functions, the problems were recorded in between 1% and 25% of the notes, but 20% to 76% of the patients reported QL impairment. Problems that were not recorded in the medical notes tended to be of low severity, with a significant trend observed for pain, fatigue, nausea/vomiting, dyspnea, loss of appetite, and physical function scale (χ2 test, 11.55 to 34.42, df = 1, P < .001).

CONCLUSION: The QL data on individual patients was consistent with the clinical records, thus providing evidence for the validity of these measures in assessment of the individual. The QL profiles had more information on symptoms and particularly on functional issues, such as emotional distress and physical performance.
Natural Killer/Natural Killer-Like T-Cell Lymphoma, CD56+, Presenting in the Skin: An Increasingly Recognized Entity With an Aggressive Course
Authors: Mraz-Gernhard Serena , Natkunam Yasodha , Hoppe Richard T. , LeBoit Philip , Kohler Sabine , Kim Youn H.
Published: February 2017

PURPOSE: To describe and identify the clinical and pathologic features of prognostic significance for natural killer (NK) and NK-like T-cell (NK/T-cell) lymphoma presenting in the skin.

PATIENTS AND METHODS: This study was a retrospective review of 30 patients with CD56+ lymphomas initially presenting with cutaneous lesions, with analysis of clinical and histopathologic parameters.

RESULTS: The median survival for all patients was 15 months. Those with extracutaneous manifestations at presentation (11 patients) had a shorter median survival of 7.6 months as compared with those without extracutaneous involvement (17 patients), who had a more favorable median survival of 44.9 months (P = .0001). Age, gender, extent of cutaneous involvement, and initial response to therapy had no statistically significant effect on survival. Seven patients (24%) had detectable Epstein-Barr virus (EBV) within neoplastic cells. The patients with tumor cells that coexpress CD30 (seven patients) have not yet reached a median survival after 35 months of follow-up as compared with those with CD30− tumor cells (20 patients), who had a median survival of 9.6 months (P < .02). Routine histopathologic characteristics had no prognostic significance nor did the presence of CD3ε, EBV, or multidrug resistance.

CONCLUSION: NK/T-cell lymphoma is an aggressive neoplasm; however, a subset with a more favorable outcome is identified in this study. The presence of extracutaneous disease at presentation is the most important clinical variable and portends a poor prognosis. The extent of initial skin involvement does not reliably predict outcome. Patients from the United States with NK/T-cell lymphoma presenting in the skin have a low incidence of demonstrable EBV in their tumor cells. Patients with coexpression of CD30 in CD56 lymphomas tend to have a more favorable outcome.
Oral Mucositis and the Clinical and Economic Outcomes of Hematopoietic Stem-Cell Transplantation
Authors: Sonis Stephen T. , Oster Gerry , Fuchs Hank , Bellm Lisa , Bradford Williamson Z. , Edelsberg John , Hayden Vanessa , Eilers June , Epstein Joel B. , LeVeque Francis G. , Miller Carole , Peterson Douglas E. , Schubert Mark M. , Spijkervet Frederik K.L. , Horowitz Mary
Published: February 2017

PURPOSE: To explore the relationship between oral mucositis and selected clinical and economic outcomes in blood and marrow transplant patients.

PATIENTS AND METHODS: Subjects consisted of 92 transplant patients from eight centers who participated in a multinational pilot study of a new oral mucositis scoring system (Oral Mucositis Assessment Scale [OMAS]). In the pilot study, patients were evaluated for erythema and ulceration/pseudomembrane formation beginning on the first day of conditioning and continuing for 28 days. We examined the relationship between patients’ peak OMAS scores and days with fever (body temperature > 38.0°C), the occurrence of significant infection, days of total parenteral nutrition (TPN), and days of injectable narcotic therapy (all over 28 days), days in hospital (over 60 days), total hospital charges for the index admission, and vital status at 100 days.

RESULTS: Patients’ peak OMAS scores spanned the full range of possible values (0 to 5) and were significantly (P < .05) correlated with all of the outcomes of interest except days with fever (P = .21). In analyses controlling for type of graft (autologous v allogeneic) and study center, a 1-point increase in peak OMAS score was associated with (1) 1.0 additional day with fever (P < .01), (2) a 2.1-fold increase in risk of significant infection (P < .01), (3) 2.7 additional days of TPN (P < .0001), (4) 2.6 additional days of injectable narcotic therapy (P < .0001), (5) 2.6 additional days in hospital (P < .01), (6) $25,405 in additional hospital charges (P < .0001), and (7) a 3.9-fold increase in 100-day mortality risk (P < .01). Mean hospital charges were $42,749 higher among patients with evidence of ulceration compared with those without (P = .06).

CONCLUSION: Oral mucositis is associated with significantly worse clinical and economic outcomes in blood and marrow transplantation.
Clinical and Pharmacologic Study of the Epirubicin and Paclitaxel Combination in Women With Metastatic Breast Cancer
Authors: Grasselli Giacomo , Viganò Lucia , Capri Giuseppe , Locatelli Alberta , Tarenzi Emiliana , Spreafico Carlo , Bertuzzi Alexia , Giani Antonio , Materazzo Carlo , Cresta Sara , Perotti Antonella , Valagussa P. , Gianni Luca
Published: February 2017

PURPOSE: A pharmacokinetic interaction may cause increased cardiotoxicity of paclitaxel (PTX) and high cumulative dose of doxorubicin. We tested antitumor activity, tolerability, and pharmacokinetics of the lesser cardiotoxic epirubicin (EPI) and PTX (ET combination).

PATIENTS AND METHODS: Twenty-seven women with untreated metastatic breast cancer, median age of 56 years, and prominent visceral involvement (74%) were studied. Three-weekly EPI (90 mg/m2) and PTX (200 mg/m2 over 3 hours) were given for a maximum nine cycles. EPI was administered 24 hours before PTX (E → T) in cycle 1, and 15 minutes before PTX (ET) thereafter. EPI, epirubicinol (EOL), EPI-glucuronide (EPI-glu), EOL-glucuronide (EOL-glu), PTX, and 6α-OH-PTX were measured in plasma and urine in 14 women.

RESULTS: Patients received 205 cycles of ET and a median EPI dose of 720 mg/m2. Grade 4 neutropenia (49% of cycles) was the most frequent toxicity. Cardiac contractility was decreased in five patients. Mild congestive heart failure occurred in two (7.4%). Response rate was 76% (28% complete). Median overall survival was 29 months. On the basis of intrapatient comparison in the first 24 hours of E → T and ET cycles, PTX did not affect EPI disposition, but significantly increased plasma exposure to EOL (by 137%), EPI-glu (threefold) and EOL-glu (twofold). Urinary excretion of EPI dose went from 8.2% in E → T to 11.8% in ET cycles. Clearance of PTX was 30% slower in ET than E → T. ET cycles caused lower neutrophil nadir than E → T (644 ± 327 v 195 ± 91, P < .05)

CONCLUSION: ET is feasible, devoid of excessive cardiac toxicity, and active. A reciprocal pharmacokinetic interference between the two drugs has pharmacodynamic consequences, and suggests a direct effect of PTX on EPI metabolism requiring ad hoc investigation.