bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Bone Single-Photon Emission Computed Tomography for Prediction of Pain Relief in Metastatic Bone Disease Treated With Rhenium-186 Etidronate
Authors: Israel Ora , Keidar Zohar , Rubinov Rafael , Iosilevski Galina , Frenkel Alex , Kuten Abraham , Betman Lise , Kolodny Gerald M. , Yarnitsky David , Front Dov
Published: February 2017

PURPOSE: To calculate radiation doses of rhenium-186 (186Re) etidronate in painful bone metastases using quantitative bone single-photon emission computed tomography (SPECT) and to determine the threshold dose for predicting pain relief. We also wanted to determine whether technetium-99m (99mTc) methylene diphosphonate (MDP) concentrations predict radiation doses of 186Re etidronate in painful lesions.

MATERIALS AND METHODS: Forty-eight patients with breast and prostate cancer were evaluated. Patients received therapeutic doses of 186Re etidronate. The area under the pain over time curve (AUPC) was measured for 8 weeks after treatment. Response was calculated as the percentage of change in AUPC. Quantitative bone SPECT (QBS)–measured concentration of 186Re etidronate was used for calculating radiation doses. Receiver operating characteristics curve analysis determined the radiation dose threshold that best separated responders from nonresponders. SPECT-measured concentration of 186Re etidronate in the urinary bladder was correlated with its concentration in the voided urine. Concentration of 99mTc MDP was compared with radiation doses to painful metastases.

RESULTS: The radiation dose threshold was 2.10 Gy. For a decrease of 50% in the AUPC, the positive predictive value (PPV) of this value was 75% and the negative predictive value (NPV) was 88%. For a decrease in pain of 33%, the PPV was 84% and the NPV was 81%. In prostate cancer patients only, the PPV was 81% and the NPV was 92%. The correlation between in vivo/in vitro measured urine concentration was 0.90. The correlation between 99mTc MDP concentration and radiation doses of 186Re etidronate was 0.92.

CONCLUSION: QBS-measured radiation doses of 186Re etidronate in painful metastases are a good predictor of pain relief. Bone SPECT using 99mTc MDP predicts radiation doses delivered by 186Re etidronate.
Phase I and Pharmacokinetic Trial of Gemcitabine in Patients With Hepatic or Renal Dysfunction: Cancer and Leukemia Group B 9565
Authors: Venook Alan P. , Egorin Merrill J. , Rosner Gary L. , Hollis Donna , Mani Sridhar , Hawkins Michael , Byrd John , Hohl Raymond , Budman Daniel , Meropol Neal J. , Ratain Mark J.
Published: February 2017

PURPOSE: To ascertain if hepatic or renal dysfunction leads to increased toxicity at a given dose of gemcitabine and to characterize the pharmacokinetics of gemcitabine and its major metabolite in patients with such dysfunction.

PATIENTS AND METHODS: Adults with tumors appropriate for gemcitabine therapy and who had abnormal liver or renal function tests were eligible. Patients were assigned to one of three treatment cohorts: I—AST level less than or equal to two times normal and bilirubin level less than 1.6 mg/dL; II—bilirubin level 1.6 to 7.0 mg/dL; and III—creatinine level 1.6 to 5.0 mg/dL with normal liver function. Doses were explored in at least three patients within each cohort. Gemcitabine and its metabolite were to be measured in the blood in all patients.

RESULTS: Forty patients were assessable for toxicity. Transient transaminase elevations were observed in many patients but were not dose limiting. Patients with AST elevations tolerated gemcitabine without increased toxicity, but patients with elevated bilirubin levels had significant deterioration in liver function after gemcitabine therapy. Patients with elevated creatinine levels had significant toxicity even at reduced doses of gemcitabine, including two instances of severe skin toxicity. There were no apparent pharmacokinetic differences among the three groups or compared with historical controls.

CONCLUSION: If gemcitabine is used for patients with elevations in AST level, no dose reduction is necessary. Patients with elevated bilirubin levels have an increased risk of hepatic toxicity, and a dose reduction is recommended. Patients with elevated creatinine levels seem to have increased sensitivity to gemcitabine, but the data are not adequate to support a specific dosing recommendation.
Retinoic Acid Receptor-Beta as a Prognostic Indicator in Stage I Non–Small-Cell Lung Cancer
Authors: Khuri Fadlo R. , Lotan Reuben , Kemp Bonnie L. , Lippman Scott M. , Wu Hong , Feng Lei , Lee J. Jack , Cooksley Catherine S. , Parr Bianca , Chang Evelyn , Walsh Garrett L. , Lee Jin S. , Hong Waun K. , Xu Xiao-Chun
Published: February 2017

PURPOSE: Retinoids are pivotal in the growth and differentiation of certain epithelial tissues, interacting with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors. RAR-beta mRNA is undetectable by in situ hybridization (ISH) in 50% of non–small-cell lung cancers (NSCLC). RAR-β may suppress tumorigenicity. Therefore, we hypothesized that loss of expression of RAR-β gene in stage I NSCLC is a prognostic factor of a poor clinical outcome.

PATIENTS AND METHODS: We retrospectively analyzed RAR-β mRNA levels (by ISH using a digoxigenin-labeled antisense riboprobe) in specimens from 185 consecutive patients with completely resected clinical/radiographic stage I NSCLC for whom clinical follow-up data were available.

RESULTS: One hundred fifty-six patients who met the criteria of pathologic stage I NSCLC and positivity for RXR-alpha mRNA (used as a control to assess RNA degradation) and who had adequate follow-up could be evaluated. RAR-β mRNA expression was undetectable in 51 patients, weakly positive in 64 patients, and strongly positive in 41 patients. Overall survival of the 41 patients with strongly positive RAR-β was significantly worse than for the 115 patients with weak or absent RAR-β (P = .045).

CONCLUSION: Unexpectedly, strong RAR-β expression was associated with a significantly worse outcome of early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding should be further explored.
Tamoxifen Should be Cost-Effective in Reducing Breast Cancer Risk in High-Risk Women
Authors: Smith Thomas J. , Hillner Bruce E.
Published: February 2017

PURPOSE: To estimate the cost-effectiveness of tamoxifen in the prevention of breast cancer.

PATIENTS AND METHODS: Clinical trial results of National Surgical Adjuvant Breast Program P−1 compared tamoxifen versus placebo in the prevention of breast cancer, and direct medical care costs were estimated from the Agency for Health Care Policy and Research and local sources. The base estimate of effectiveness included all women on the trial.

RESULTS: For every 100 women treated for 5 years, 1.665 expected cancers would not be detected. If breast cancer death is fully prevented by this strategy, then the cost-effectiveness of tamoxifen compared with no intervention is $8,479 per additional year of life gained. If lifetime prevention of the risk of death from breast cancer exceeded 17%, then the cost-effectiveness ratio would be less than $50,000 per year of life gained (a common benchmark).

CONCLUSIONS: Tamoxifen for breast cancer prevention should be cost-effective under nearly all circumstances. Its use will require additional resources because it is not cost saving, but it fits within accepted guidelines.
New Malignant Diseases After Allogeneic Marrow Transplantation for Childhood Acute Leukemia
Authors: Socié Gérard , Curtis Rochelle E. , Deeg H. Joachim , Sobocinski Kathleen A. , Filipovich Alexandra H. , Travis Lois B. , Sullivan Keith M. , Rowlings Philip A. , Kingma Douglas W. , Banks Peter M. , Travis William D. , Witherspoon Robert P. , Sanders Jean , Jaffe Elaine S. , Horowitz Mary M.
Published: February 2017

PURPOSE: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia.

PATIENTS AND METHODS: We studied a cohort of 3,182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression.

RESULTS: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P < .001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7.5), T-cell–depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1).

CONCLUSION: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers.
Effect of Adjuvant Tamoxifen on the Endometrium in Women With Breast Cancer: A Prospective Study Using Office Endometrial Biopsy
Authors: Barakat R.R. , Gilewski T.A. , Almadrones L. , Saigo P.E. , Venkatraman E. , Hudis C. , Hoskins W.J.
Published: February 2017

PURPOSE: To determine the frequency of developing abnormal pathologic changes in the endometria of tamoxifen-treated women. To characterize the type of pathologic changes involved.

PATIENTS AND METHODS: Between October 1991 and September 1998, 159 patients initiating tamoxifen therapy for breast cancer confined to the breast and axillary lymph nodes were entered in a prospective study. In this study, office endometrial biopsies (EMBs) were obtained during the initiation of tamoxifen and at 6-month intervals for a 2-year period. Three subsequent annual EMBs were recorded for each patient, amounting to a 5-year surveillance.

RESULTS: One hundred fifty-nine patients with a median age of 50 years were entered onto study. Patients were assessable if EMBs were performed at least 1 year after the initiation of tamoxifen treatment. Nine patients (5.7%) were considered protocol violations. The remaining 111 assessable patients underwent a total of 635 EMBs (mean, 5.8 EMBs), with a median surveillance time of 36 months. Eighty-two (12.9%) of the 635 biopsies revealed tissue insufficient for diagnosis. Fourteen patients (12.6%) underwent dilation and curettage (D&C) for an abnormal EMB, persistent bleeding, or for evaluation of adnexal masses at the time of laparoscopy. Findings at D&C included complex hyperplasia (n = 1), abnormal histiocytes (n = 1), simple hyperplasia (n = 2), polyps (n = 4), endocervical polyp (n = 1), and decidualization (n = 2). Three D&Cs were negative. Three patients have undergone hysterectomy.

CONCLUSION: EMB was used to monitor the endometrium in the majority (95%) of breast cancer patients on tamoxifen in this trial, but the utility of routine EMB for screening in tamoxifen-treated women seems limited.
In Vivo Cytoreduction Studies and Cell Sorting–Enhanced Tumor-Cell Detection in High-Risk Neuroblastoma Patients: Implications for Leukapheresis Strategies
Authors: Faulkner Lawrence B. , Garaventa Alberto , Paoli Antonella , Tintori Veronica , Tamburini Angela , Lacitignola Laura , Veltroni Marinella , Piccolo Maria Serena Lo , Viscardi Elisabetta , Milanaccio Claudia , Tondo Annalisa , Spinelli Serena , Bernini Gabriella , De Bernardi Bruno
Published: February 2017

PURPOSE: To improve autologous leukapheresis strategies in high-risk neuroblastoma (NB) patients with extensive bone marrow involvement at diagnosis.

PATIENTS AND METHODS: Anti-GD2 immunocytochemistry (sensitivity, 1 in 105 to 106 leukocytes) was used to evaluate blood and bone marrow disease at diagnosis and during the recovery phase of the first six chemotherapy cycles in 57 patients with stage 4 NB and bone marrow disease at diagnosis. A total of 42 leukapheresis samples from the same patients were evaluated with immunocytology, and in 24 of these patients, an anti-GD2 immunomagnetic enrichment step was used to enhance tumor-cell detection.

RESULTS: Tumor cytoreduction was much faster in blood compared with bone marrow (3.2 logs after the first cycle and 2.1 logs after the first two cycles, respectively). Bone marrow disease was often detectable throughout induction, with a trend to plateau after the fourth cycle. By direct anti-GD2 immunocytology, a positive leukapheresis sample was obtained in 7% of patients after either the fifth or sixth cycle; when NB cell immunomagnetic enrichment was applied, 25% of patients had a positive leukapheresis sample (sensitivity, 1 in 107 to 108 leukocytes).

CONCLUSION: Standard chemotherapy seems to deliver most of its in vivo purging effect within the first four cycles. In patients with overt marrow disease at diagnosis, postponing hematopoietic stem-cell collection beyond this point may not be justified. Tumor-cell clearance in blood seems to be quite rapid, and earlier collections via peripheral-blood leukapheresis might be feasible. Immunomagnetically enhanced NB cell detection can be highly sensitive and can indicate whether ex vivo purging should be considered.
Abnormalities of Chromosome Bands 13q12 to 13q14 in Childhood Acute Lymphoblastic Leukemia
Authors: Heerema Nyla A. , Sather Harland N. , Sensel Martha G. , Lee Mei K. , Hutchinson Raymond J. , Nachman James B. , Reaman Gregory H. , Lange Beverly J. , Steinherz Peter G. , Bostrom Bruce C. , Gaynon Paul S. , Uckun Fatih M.
Published: February 2017

PURPOSE: Little is known about nonrandom deletions of chromosome bands 13q12 to 13q14 (13q12–14) in acute lymphoblastic leukemia (ALL). We determined the prognostic significance of cytogenetically identified breakpoints in 13q12–14 in children with newly diagnosed ALL treated on Children’s Cancer Group protocols from 1988 to 1995.

PATIENTS AND METHODS: Breakpoints in 13q12–14 were identified in 36 (2%) of the 1,946 cases with accepted cytogenetic data. Outcome analysis used standard life-table methods.

RESULTS: Seventeen patients (47%) with an abnormal 13q12–14 were classified, according to the National Cancer Institute (NCI), as poor risk, and 15 patients (42%) were standard risk; four (11%) were infants less than 12 months of age. Eight cases had balanced rearrangements of 13q12–14, 27 patients had a partial loss of 13q, and one had both a partial gain and a partial loss. The most frequent additional abnormalities among these patients were an abnormal 12p, a del(6q), a del(9p), a 14q11 breakpoint, and an 11q23 breakpoint. Nineteen patients were pseudodiploid, 10 were hyperdiploid, and seven were hypodiploid. Patients with an abnormal 13q12–14 had significantly worse event-free survival than patients lacking such an abnormality, with estimates at 6 years of 61% (SD = 14%) and 74% (SD = 1%), respectively (P = .04; relative risk = 1.74). Overall survival, however, was similar for the two groups (P = .25). The prognostic effect of an abnormal 13q was attenuated in a multivariate analysis adjusted for NCI risk status and ploidy (P = .72).

CONCLUSION: Aberrations of 13q12–14 may contribute to leukemogenesis of childhood ALL and confer increased risk of treatment failure but are associated with other poor-risk features.
Large-Cell Lymphoma Arising in the Mediastinum in Children and Adolescents Is Associated With an Excellent Outcome: A Children’s Cancer Group Report
Authors: Lones Mark A. , Perkins Sherrie L. , Sposto Richard , Kadin Marshall E. , Kjeldsberg Carl R. , Wilson John F. , Cairo Mitchell S.
Published: February 2017

PURPOSE: Large-cell lymphoma (LCL) arising in the mediastinum (LCL-M) is a heterogeneous group of non-Hodgkin’s lymphoma (NHL) that includes B-cell lymphomas as well as T-cell lymphomas, including anaplastic LCL. LCL-M is well recognized in young adults but is less well characterized and infrequent in children and adolescents.

METHODS: A retrospective review of Children’s Cancer Group therapeutic studies for nonlymphoblastic lymphomas (CCG-551, CCG-503, CCG-552, and CCG-5911) identified 20 patients with LCL-M, representing 7.2% of all LCLs classified by central pathology review.

RESULTS: The patients ranged in age from 4 to 19 years (median, 12.5 years; mean, 12 years); 55% of the patients were male. Although a variety of chemotherapy regimens were used, response was excellent, with all 20 patients (100%) achieving a complete response. Four patients (20%) experienced relapse locally or in distant sites including brain and kidney. One patient died of sepsis during therapy. For the 20 patients with LCL-M, the product-limit estimated 5-year event-free survival (EFS) and 5-year overall survival (OS) rates are 75% ± 10% and 85% ± 8%, respectively. For disseminated LCLs (192 cases), the EFS and OS rates were 50% ± 4% and 63% ± 4%, respectively, which differ significantly from the those of the LCL-M cases (EFS, P = .025; OS, P = .034). The 5-year EFS and OS rates for patients with localized LCL (67 cases) were 92 ± 3% and 97 ± 2%, respectively.

CONCLUSION: LCL-M is a heterogeneous group of NHLs that makes up approximately 7.2% of LCL in children and adolescents. Response to therapy and OS in this young age group seems excellent and superior to that of disseminated LCLs but inferior to that of other localized LCL. Future studies of LCL-M will evaluate short intense chemotherapy administered without radiation therapy.
Adenovirus-Mediated p53 Gene Transfer in Sequence With Cisplatin to Tumors of Patients With Non–Small-Cell Lung Cancer
Authors: Nemunaitis J. , Swisher S.G. , Timmons T. , Connors D. , Mack M. , Doerksen L. , Weill D. , Wait J. , Lawrence D.D. , Kemp B.L. , Fossella F. , Glisson B.S. , Hong W.K. , Khuri F.R. , Kurie J.M. , Lee J.J. , Lee J.S. , Nguyen D.M. , Nesbitt J.C. , Perez-Soler R. , Pisters K.M. W. , Putnam J.B. , Richli W.R. , Shin D.M. , Walsh G.L. , Merritt J. , Roth J.
Published: February 2017

PURPOSE: To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection in patients with non–small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Patients with advanced NSCLC and abnormal p53 function were enrolled onto cohorts receiving escalating dose levels of Adp53 (1 × 106 to 1 × 1011 plaque-forming units [PFU]). Patients were administered intravenous cisplatin 80 mg/m2 on day 1 and study vector on day 4 for a total of up to six courses (28 days per course). Apoptosis was determined by the terminal deoxynucleotidyl- transferase-dUTP nick–end labeling assay. Evidence of vector-specific sequences were determined using reverse-transcriptase polymerase chain reaction. Vector dissemination and biodistribution was monitored using a series of assays (cytopathic effects assay, Ad5 hexon enzyme-linked immunosorbent assay, vector-specific polymerase chain reaction assay, and antibody response assay).

RESULTS: Twenty-four patients (median age, 64 years) received a total of 83 intratumor injections with Adp53. The maximum dose administered was 1 × 1011 PFU per dose. Transient fever related to Adp53 injection developed in eight of 24 patients. Seventeen patients achieved a best clinical response of stable disease, two patients achieved a partial response, four patients had progressive disease, and one patient was not assessable. A mean apoptotic index between baseline and follow-up measurements increased from 0.010 to 0.044 (P = .011). Intratumor transgene mRNA was identified in 43% of assessable patients.

CONCLUSION: Intratumoral injection with Adp53 in combination with cisplatin is well tolerated, and there is evidence of clinical activity.
Value of Estrogenic Recruitment Before Chemotherapy: First Randomized Trial in Primary Breast Cancer
Authors: Bontenbal M. , van Putten W.L. J. , Burghouts J. Th. M. , Baggen M.G. A. , Ras G.J. , Stiegelis W.F. , Beudeker M. , Janssen J. Th. P. , Braun J.J. , van der Linden G.H. M. , van der Velden P.C. , van Geel A.N. , Helle P. , Leisink M. , Foekens J.A. , Klijn J.G. M.
Published: February 2017

PURPOSE: Several preclinical studies showed that short-term pretreatment of breast cancer cells with estrogens can increase the antitumor efficacy of different cytotoxic drugs. Some early clinical studies in patients with advanced breast cancer did seem to support these findings. Therefore, the efficacy of estrogenic recruitment followed by chemotherapy was compared with that of chemotherapy alone in a randomized phase III study in women with lymph node–positive primary breast cancer.

PATIENTS AND METHODS: Three hundred twenty-eight patients with stage II/IIIA breast cancer who were younger than 66 years of age were randomly allocated to chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC) or FAC plus pretreatment with ethinyl estradiol (EE2). FAC (500, 50, and 500 mg/m2, respectively) was administered intravenously once every 4 weeks for four cycles. EE2 (0.5 mg) was administered orally, both 24 hours and immediately preceding FAC chemotherapy.

RESULTS: Patient and tumor characteristics and chemotherapy dosages were comparable in both treatment groups. Of 318 assessable patients, with a median follow-up of 6.8 years, 177 patients had a relapse and 127 died. No significant differences were observed between the two treatment groups with respect to relapse-free, local recurrence–free, and overall survival according to univariate and multivariate analyses adjusted for age, menopausal status, tumor size, grade, number of positive nodes, and steroid-receptor status. The power for the detection of an increase of 50% in the median relapse-free survival was 80%.

CONCLUSION: Estrogenic recruitment of breast cancer cells before FAC chemotherapy did not influence the efficacy of adjuvant chemotherapy in stage II/IIIA breast cancer patients after a follow-up of 6.8 years.
Phase I Study of Fludarabine Plus Cyclophosphamide in Patients With Previously Untreated Low-Grade Lymphoma: Results and and Long-Term Follow-Up—A Report From the Eastern Cooperative Oncology Group
Authors: Hochster Howard S. , Oken Martin M. , Winter Jane N. , Gordon Leo I. , Raphael Bruce G. , Bennett John M. , Cassileth Peter A.
Published: February 2017

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma.

PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg/m2. Fludarabine 20 mg/m2 was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required.

RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m2), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively.

CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg/m2 day 1 and fludarabine 20 mg/m2 days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.
Partially Mismatched Related-Donor Bone Marrow Transplantation for Pediatric Patients With Acute Leukemia: Younger Donors and Absence of Peripheral Blasts Improve Outcome
Authors: Godder K.T. , Hazlett L.J. , Abhyankar S.H. , Chiang K.Y. , Christiansen N.P. , Bridges K.D. , Lee C.G. , Geier S.S. , Goon-Johnson K.S. , Gee A.P. , Pati A.R. , Parrish R.S. , Henslee-Downey P.J.
Published: February 2017

PURPOSE: To extend access to bone marrow transplantation (BMT), we used partially mismatched related donors (PMRD) for pediatric patients with acute leukemia. In this report we sought to determine pretransplantation factors that might predict outcome.

PATIENTS AND METHODS: Of 67 such patients, 43 had acute lymphocytic leukemia and 24 had acute myelogenous leukemia. At the time of transplantation, 41 patients were in relapse. Donors included 40 parents, 24 siblings, and three cousins. HLA disparity of two to three major antigens was detected in two thirds of the donor-recipient pairs. Conditioning therapy, including total-body irradiation and chemotherapy followed by graft-versus-host disease (GvHD) prophylaxis with partial T-cell depletion of the graft using T10B9 or OKT3, was combined with posttransplantation immunosuppression.

RESULTS: Estimated probability (EP) of engraftment was 0.96 and was not affected by donor-antigen mismatch (AgMM; P = .732). EP of grades 2 to 4 acute GvHD was 0.24 and was not affected by recipient AgMM (P = .796). EP of disease-free survival was 0.26 at 3 years but improved to 0.45 when donors were younger than 30 years (P < .001). EP of relapse at 3 years was 0.41 and reduced with younger donors’ age. For patients who were in relapse at the time of transplantation, absence of blasts was associated with a lower relapse rate (0.46 v 0.84; P = .083), similar to that of patients in remission.

CONCLUSION: PMRD-BMT in pediatric leukemia resulted in high engraftment and low GvHD rates. To improve outcomes, younger donors should be sought, and clinicians should attempt to reduce peripheral blasts in patients who are in relapse.
Feasibility of Quantitative Pain Assessment in Outpatient Oncology Practice
Authors: Rhodes Deborah J. , Koshy Rachel C. , Waterfield William C. , Wu Albert W. , Grossman Stuart A.
Published: February 2017

PURPOSE: Although physicians view failure to assess pain systematically as the most important barrier to outpatient cancer pain management, little is known about pain assessment in this setting. We sought to determine whether pain is routinely assessed and whether routine quantitative pain assessment is feasible in a busy outpatient oncology practice.

PATIENTS AND METHODS: We conducted a pre- and postintervention chart review of 520 randomly selected medical and radiation oncology patient visits at a community hospital-based private outpatient practice. The intervention consisted of training health assistants (HAs) to measure and document patient pain scores by using a visual analog scale. The main outcome measures included HA documentation of patient pain scores, quantitative and qualitative mention of pain in the physician note, and analgesic treatment before and after the intervention.

RESULTS: After the intervention, HA documentation of pain scores increased from 1% to 75.6% (P < .0001). Physician documentation increased from 0% to 4.8% for quantitative documentation (P < .01), and from 60.0% to 68.3% for qualitative documentation (not significant). Of all the patients, 23.1% reported significant pain. Subgroups with greater pain included patients actively receiving radiation treatments and patients with lung cancer. Of patients with signifi-cant pain, 28.2% had no mention of pain in the physician note and 47.9% had no documented analgesic treatment.

CONCLUSION: Quantitative pain assessment was virtually absent before our intervention but easily implemented and sustained in a busy outpatient oncology practice. Pain score collection identified a high prevalence of pain, patient subgroups at risk for pain, and a significant proportion of patients with pain that was neither evaluated nor treated by their oncologists.
T1-T2N0 Squamous Cell Carcinoma of the Glottic Larynx Treated With Radiation Therapy
Authors: Mendenhall William M. , Amdur Robert J. , Morris Christopher G. , Hinerman Russell W.
Published: February 2017

PURPOSE: The end results after radiation therapy for T1-T2N0 glottic carcinoma vary considerably. We analyze patient-related and treatment-related parameters that may influence the likelihood of cure.

PATIENTS AND METHODS: Five hundred nineteen patients were treated with radiation therapy and had follow-up for ≥ 2 years. Three patients who were disease-free were lost to follow-up at 7 months, 21 months, and 10.5 years. No other patients were lost to follow-up.

RESULTS: Local control rates at 5 years after radiation therapy were as follows: T1A, 94%; T1B, 93%; T2A, 80%; and T2B, 72%. Multivariate analysis of local control revealed that the following parameters significantly influenced this end point: overall treatment time (P < .0001), T stage (P = .0003), and histologic differentiation (P = .013). Patients with poorly differentiated cancers fared less well than those with better differentiated lesions. Rates of local control with laryngeal preservation at 5 years were as follows: T1A and T1B, 95%; T2A, 82%; and T2B, 76%. Cause-specific survival rates at 5 years were as follows: T1A and T1B, 98%; T2A, 95%; and T2B, 90%. One patient with a T1N0 cancer and three patients with T2N0 lesions experienced severe late radiation complications.

CONCLUSION: Radiation therapy cures a high percentage of patients with T1-T2N0 glottic carcinomas and has a low rate of severe complications. The major treatment-related parameter that influences the likelihood of cure is overall treatment time.
Structured Exercise Improves Physical Functioning in Women With Stages I and II Breast Cancer: Results of a Randomized Controlled Trial
Authors: Segal Roanne , Evans William , Johnson Darren , Smith Julie , Colletta Sal , Gayton Jane , Woodard Stephanie , Wells George , Reid Robert
Published: February 2017

PURPOSE: Self-directed and supervised exercise were compared with usual care in a clinical trial designed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer.

PATIENTS AND METHODS: One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life, aerobic capacity, and body weight. Participants were randomly allocated to one of three intervention groups: usual care (control group), self-directed exercise, or supervised exercise. Quality of life, aerobic capacity, and body weight measures were repeated at 26 weeks. The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks.

RESULTS: Physical functioning in the control group decreased by 4.1 points, whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups, respectively (P = .04). Post hoc analysis showed a moderately large (and clinically important) difference between the self-directed and control groups (9.8 points; P = .01) and a more modest difference between the supervised and control groups (6.3 points; P = .09). No significant differences between groups were observed for changes in quality of life scores. In a secondary analysis of participants stratified by type of adjuvant therapy, supervised exercise improved aerobic capacity (+3.5 mL/kg/min; P = .01) and reduced body weight (−4.8 kg; P < .05) compared with usual care only in participants not receiving chemotherapy.

CONCLUSION: Physical exercise can blunt some of the negative side effects of breast cancer treatment, including reduced physical functioning. Self-directed exercise is an effective way to improve physical functioning compared with usual care. In participants not receiving chemotherapy, supervised exercise may increase aerobic capacity and reduce body weight compared with usual care.
Role of Postchemotherapy Adjunctive Surgery in the Management of Patients With Nonseminoma Arising From the Mediastinum
Authors: Vuky Jacqueline , Bains Manjit , Bacik Jennifer , Higgins Geralyn , Bajorin Dean F. , Mazumdar Madhu , Bosl George J. , Motzer Robert J.
Published: February 2017

PURPOSE: To evaluate the role of postchemotherapy surgery in patients with nonseminomatous germ cell tumors arising from the anterior mediastinum.

PATIENTS AND METHODS: Thirty-two patients with nonseminoma arising from a mediastinal primary site were treated on a clinical trial at our center, and they underwent postchemotherapy surgery. The results of postchemotherapy surgical resection, frequency of viable tumor found during postchemotherapy surgery, and prognostic factors for survival were assessed.

RESULTS: Complete resection of all gross residual disease was achieved in 27 patients (84%). Histologic analysis of resected residua postchemotherapy revealed viable tumor in 66%, teratoma in 22%, and necrosis in 12% of the specimens. Viable tumor included embryonal carcinoma, choriocarcinoma, yolk sac carcinoma, seminoma, and teratoma with malignant transformation to nongerm cell histology (eg, sarcoma). Clinical characteristics associated with a shorter survival after surgery included the presence of viable tumor in a resected specimen (P = .003) and more than one site resected during surgery (P = .06). There were no statistically significant differences in survival for patients who underwent surgical resection with normal markers compared with patients with elevated serum tumor markers (P = .33). A trend toward shorter survival was found in patients with increasing tumor markers before surgery compared with patients with normal and declining serum tumor markers (P = .09).

CONCLUSION: Surgical resection of residual mass after chemotherapy plays an integral role in the management of patients with primary mediastinal nonseminoma. Teratoma and viable tumor were found in the majority of resected residua after chemotherapy. Because patients who undergo conventional salvage chemotherapy programs rarely achieve long-term disease-free status, selected patients with elevated markers after chemotherapy are considered candidates for surgical resection.
73.6 Gy and Beyond: Hyperfractionated, Accelerated Radiotherapy for Non–Small-Cell Lung Cancer
Authors: Maguire Patrick D. , Marks Lawrence B. , Sibley Gregory S. , Herndon II James E. , Clough Robert W. , Light Kim L. , Hernando Maria L. , Antoine Philip A. , Anscher Mitchell S.
Published: February 2017

PURPOSE: To assess results with twice-daily high-dose radiotherapy (RT) for non–small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Between 1991 and 1998, 94 patients with unresectable NSCLC were prescribed ≥ 73.6 Gy via accelerated fractionation. Fifty were on a phase II protocol (P group); 44 were similarly treated off-protocol (NP group). The clinical target volume received 45 Gy at 1.25 Gy bid (6-hour interval). The gross target volume received 1.6 Gy bid to 73.6 to 80 Gy over 4.5 to 5 weeks using a concurrent boost technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated by the Kaplan-Meier method. Median follow-up durations for surviving P and NP patients were 67 and 16 months, respectively.

RESULTS: Total doses received were ≥ 72 Gy in 97% of patients. The median OS by stage was 34, 13, and 12 months for stages I/II, IIIa, and IIIb, respectively. LPFS was significantly longer for patients with T1 lesions (median, 43 months) versus T2-4 (median, 7 to 10 months; P = .01). Results were similar in the P and NP groups. Acute grade ≥ 3 toxicity included esophagus (14 patients; 15%), lung (three patients; 3% [one grade 5]), and skin (four patients; 4%). Grade ≥ 3 late toxicity in 86 assessable patients included esophagus (three patients; 3%), lung (15 patients; 17% [three grade 5]), skin (five patients; 6%), heart (two patients; 2%), and nerve (one patient; 1%).

CONCLUSION: This regimen yielded favorable survival results, particularly for T1 lesions. Acute grade ≥ 3 toxicity seems greater than for conventional RT, though most patients recovered. Late grade ≥ 3 pulmonary toxicity occurred in 17%. Because of continued locoregional recurrences, we are currently using doses ≥ 86 Gy.
Use of Hematopoietic Progenitors in Whole Blood to Support Dose-Dense Chemotherapy: A Randomized Phase II Trial in Small-Cell Lung Cancer Patients
Authors: Woll Penella J. , Thatcher Nicholas , Lomax Lynn , Hodgetts Jackie , Lee S. Ming , Burt Paul A. , Stout Ronald , Simms Tanya , Davies Rowena , Pettengell Ruth
Published: February 2017

PURPOSE: Small-cell lung cancer (SCLC) is exquisitely chemosensitive, but few patients are cured by conventional chemoradiotherapy. Recent studies suggest that increased cytotoxic dose-intensity might improve survival. In this randomized phase II study, we tested the feasibility of dose intensification using sequential reinfusion of hematopoietic progenitors in whole blood.

PATIENTS AND METHODS: SCLC patients with a favorable prognosis were treated with six cycles of ifosfamide, carboplatin, and etoposide (ICE), at 4-week (standard treatment) or 2-week (intensified treatment) intervals. Intensified treatment was supported by daily subcutaneous filgrastim injections and reinfusion of 750 mL of autologous blood collected immediately before each cycle.

RESULTS: Fifty consecutive patients were randomized to standard (n = 25) or intensified (n = 25) ICE. A total of 94% completed at least three treatment cycles, and 70% completed six cycles; 96% of treatments were given at full dose. The planned dose-intensity was 1.0 for standard and 2.0 for intensified ICE. The median received dose-intensity for cycles 1 through 3 was 0.99 (range, 0.33 to 1.02) for the standard treatment arm and 1.80 (range, 0.99 to 1.97) for the intensified treatment arm (P < .001). Over all six cycles, the median received dose-intensity was 0.95 (range, 0.17 to 1.03) for the standard treatment arm and 1.60 (range, 0.60 to 2.01) for the intensified treatment arm (P < .001). Febrile neutropenia was more common on the standard treatment arm (84% v 56%), resulting in more days of intravenous antibiotics (median, 10 v 3 days; P = .035). Transfusion requirements were similar in the two groups.

CONCLUSION: Sequential reinfusion of hematopoietic progenitors in whole blood can safely support substantial increases in dose-intensity of ICE chemotherapy for SCLC.
Neutropenic Enterocolitis in Patients With Acute Leukemia: Prognostic Significance of Bowel Wall Thickening Detected by Ultrasonography
Authors: Cartoni Claudio , Dragoni Francesco , Micozzi Alessandra , Pescarmona Edoardo , Mecarocci Sergio , Chirletti Piero , Petti Maria Concetta , Meloni Giovanna , Mandelli Franco
Published: February 2017

PURPOSE: Neutropenic enterocolitis (NE) is a severe complication of intensive chemotherapy and is barely identifiable by clinical signs alone. Ultrasonography (US) supports the diagnosis of NE by showing pathologic thickening of the bowel wall. The aim of this study was to evaluate the prognostic value of the degree of mural thickening evaluated by US in patients with clinically suspected NE.

PATIENTS AND METHODS: Neutropenic patients with fever, diarrhea, and abdominal pain after intensive chemotherapy for hematologic malignancies were studied with abdominal US. We evaluated the degree of bowel wall thickening detected by US and its correlation with the duration of the clinical syndrome as well as NE-related mortality.

RESULTS: Eighty-eight (6%) of 1,450 consecutive patients treated for leukemia had clinical signs of NE. In 44 (50%) of 88 patients, US revealed pathologic wall thickening (mean ± SD, 10.2 ± 2.9 mm; range, 6 to 18). The mean duration of symptoms was significantly longer in this group (7.9 days) than among patients without mural thickening (3.8 days, P < .0001), and the NE-related mortality rate was higher (29.5% v 0%, P < .001). Patients with bowel wall thickness of more than 10 mm had a significantly higher mortality rate (60%) than did those with bowel wall thickness ≤ 10 mm (4.2%, P < .001).

CONCLUSION: Symptomatic patients with sonographically detected bowel wall thickening have a poor prognosis compared with patients without this finding. In addition, mural thickness of more than 10 mm is associated with poorer outcome among patients with NE.
Prediction of Response to Salvage Radiation Therapy in Patients With Prostate Cancer Recurrence After Radical Prostatectomy
Authors: Leventis Angelos K. , Shariat Shahrokh F. , Kattan Michael W. , Butler E. Brian , Wheeler Thomas M. , Slawin Kevin M.
Published: February 2017

PURPOSE: To identify factors predictive of local recurrence as defined by a complete response to salvage radiation therapy in patients whose disease recurs after radical prostatectomy.

PATIENTS AND METHODS: Ninety-five patients with recurrence after radical prostatectomy who were evaluated by prostatic fossa biopsies, and a subset of 49 of these patients treated with radiation for control of presumed or biopsy-proven local recurrence, were studied.

RESULTS: Biopsies were positive in 40 (42%) of the 95 biopsied patients. Multivariate analysis revealed that prebiopsy prostate-specific antigen (PSA) level, postrecurrence PSA doubling time, and positive digital rectal examination (DRE) of the prostatic fossa were all statistically significant predictors of a positive biopsy. For the 49 patients subsequently treated with salvage radiation therapy, the overall actuarial 3- and 5-year PSA relapse-free probabilities were 43% and 24%, respectively. Univariate analysis showed no differences in the PSA relapse-free probabilities associated with any pathologic features of the radical prostatectomy specimen, biopsy confirmation of local recurrence, or DRE of the prostatic fossa. In multivariate analysis, controlling for all other variables, preradiation PSA and postrecurrence PSA doubling time measured before radiation were the only statistically significant predictors of outcome.

CONCLUSION: DRE of the prostatic fossa, prebiopsy PSA, and postrecurrence PSA doubling time predict which patients will have biopsy-proven local recurrence. However, response to salvage radiation therapy is associated with postrecurrence PSA doubling time and with preradiation PSA level only. DRE of the prostatic fossa and biopsy confirmation of local recurrence are not associated with salvage radiation outcome.
Equivalence of Three or Four Cycles of Bleomycin, Etoposide, and Cisplatin Chemotherapy and of a 3- or 5-Day Schedule in Good-Prognosis Germ Cell Cancer: A Randomized Study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council
Authors: de Wit Ronald , Roberts J. Trevor , Wilkinson Peter M. , de Mulder Pieter H.M. , Mead Graham M. , Fosså Sophie D. , Cook Pat , de Prijck Linda , Stenning Sally , Collette Laurence
Published: February 2017

PURPOSE: To test the equivalence of three versus four cycles of bleomycin, etoposide, and cisplatin (BEP) and of the 5-day schedule versus 3 days per cycle in good-prognosis germ cell cancer.

PATIENTS AND METHODS: The study was designed as a 2 × 2 factorial trial. The aim was to rule out a 5% decrease in the 2-year progression-free survival (PFS) rate. The study included the assessment of patient quality of life. A cycle of BEP consisted of etoposide 500 mg/m2, administered at either 100 mg/m2 days 1 through 5 or 165 mg/m2 days 1 through 3, cisplatin 100 mg/m2, administered at either 20 mg/m2 days 1 through 5 or 50 mg/m2 days 1 and 2. Bleomycin 30 mg was administered on days 1, 8, and 15 during cycles 1 through 3. The randomization procedure allowed some investigators to participate only in the comparison of three versus four cycles.

RESULTS: From March 1995 until April 1998, 812 patients were randomly assigned to receive three or four cycles: of these, 681 were also randomly assigned to the 5-day or the 3-day schedule. Histology, marker values, and disease extent are well balanced in the treatment arms of the two comparisons. The projected 2-year PFS is 90.4% on three cycles and 89.4% on four cycles. The difference in PFS between three and four cycles is −1.0% (80% confidence limit [CL], −3.8%, +1.8%). Equivalence for three versus four cycles is claimed because both the upper and lower bounds of the 80% CL are less than 5%. In the 5- versus 3-day comparison, the projected 2-year PFS is 88.8% and 89.7%, respectively (difference, −0.9%, (80% CL, −4.1%, +2.2%). Hence, equivalence is claimed in this comparison also. Frequencies of hematologic and nonhematologic toxicities were essentially similar. Quality of life was maintained better in patients receiving three cycles; no differences were detected between 3 and 5 days of treatment.

CONCLUSION: We conclude that three cycles of BEP, with etoposide at 500 mg/m2, is sufficient therapy in good-prognosis germ cell cancer and that the administration of the chemotherapy in 3 days has no detrimental effect on the effectiveness of the BEP regimen.
Phase I Study of Stealth Liposomal Doxorubicin in Combination With Gemcitabine in the Treatment of Patients With Metastatic Breast Cancer
Authors: Rivera Edgardo , Valero Vicente , Syrewicz Laura , Rahman Zia , Esteva Francisco L. , Theriault Richard L. , Rosales Marguerite M. , Booser Daniel , Murray James L. , Bast Robert C. , Hortobagyi Gabriel N.
Published: February 2017

PURPOSE: We conducted a single-institution phase I clinical trial to determine the maximum-tolerated dose (MTD) and define the toxic effects of stealth liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer.

PATIENTS AND METHODS: Patients were eligible if they had disease progression with no limit on prior number of chemotherapy regimens. Prior treatment with liposomal doxorubicin and/or gemcitabine was not allowed. The starting dose of liposomal doxorubicin was 20 mg/m2 on day 1 only with a 20% dose escalation of the previous mg/m2 dose until MTD was reached. Gemcitabine was given as a fixed dose of 800 mg/m2 on days 1 and 8 every 3 weeks.

RESULTS: We treated 27 patients of whom six had never received chemotherapy for their disease. Most had had visceral involvement as their dominant site of disease. The dose-limiting toxicity was myelosuppression, which included neutropenia and thrombocytopenia. However, neither neutropenic fever nor episodes of bleeding were major occurrences. Significant antitumor activity was also observed with a total of two complete and seven partial responses. The recommended phase II dose is liposomal doxorubicin 24 mg/m2 on day 1 and gemcitabine 800 mg/m2 on days 1 and 8 every 21 days.

CONCLUSION: The combination of liposomal doxorubicin and gemcitabine is an active and well tolerated regimen when administered on a 21-day schedule. Myelosuppression limited further dose escalation, however, it did not increase the incidence of neutropenic fever. Significant antitumor activity seen in heavily and minimally pretreated patients warrants further evaluation of this combination.