bluuebunny/crossref_metadata_2025 huggingface dataset:
Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation?
Authors: Jansson T , Westlin J E , Ahlström H , Lilja A , Långström B , Bergh J
Published: February 2017

PURPOSE

To investigate if sequential positron emission tomographic (PET) scans with the glucose analog 18F-2-fluoro-2-deoxy-D-glucose (18FDG) and/or L-methyl-11C-methionine (11C-methionine) in patients with breast cancer could provide early information on the efficacy of polychemotherapy.

PATIENTS AND METHODS

Sixteen patients with breast cancer (11 with locally advanced tumors, three with recurrent disease in the contralateral breast, two of them with distant and regional metastases, and two with distant metastases) underwent a baseline and two follow-up PET scans after the first and third/fourth polychemotherapy course. Tumor response was determined clinically/radiographically after three/four polychemotherapy courses.

RESULTS

Five patients were investigated with 18FDG, seven with both 11C-methionine and 18FDG, and four with only 11C-methionine before polychemotherapy. 11C-methionine presented a more distinct visualization of primary/contralateral breast cancers in five of seven patients when compared with 18FDG. Twelve of 16 patients demonstrated a response using conventional methods after the third/fourth course of polychemotherapy. Eight of these 12 clinical responders had a significant decrease in tracer uptake at the first PET scan performed 6 to 13 days after the first polychemotherapy course, and these reductions were further augmented after the third/fourth course and corresponded to the conventional therapy evaluation (clinical examination, computed tomography [CT], ultrasonography, and mammography).

CONCLUSION

Our data indicate that PET may be of clinical value in predicting response to chemotherapy in patients with locally advanced breast cancer and/or metastatic disease earlier than any other method used.
Randomized trial of neoadjuvant cisplatin and fluorouracil versus carboplatin and fluorouracil in patients with stage IV-M0 head and neck cancer.
Authors: De Andrés L , Brunet J , López-Pousa A , Burgués J , Vega M , Tabernero J M , Mesía R , López J J
Published: February 2017

PURPOSE

A randomized trial was designed to compare cisplatin (CDDP) and fluorouracil (FU) versus carboplatin (CBDCA) and FU as neoadjuvant treatment in stage IV-M0 head and neck cancer to assess whether CBDCA-FU is better than CDDP-FU with regard to response and toxicity.

PATIENTS AND METHODS

Patients were randomized to receive CDDP 100 mg/m2 intravenously on day 1 and FU 5,000 mg/m2 over a 120-hour continuous infusion, or CBDCA 400 mg/m2 over a 24-hour continuous infusion on day 1 and FU with the same schedule. Both regimens were repeated every 21 days. The patients received three courses of chemotherapy, excluding those who failed to achieve a partial response (PR) after the second course. Complete responders were treated with radiotherapy. The remaining patients underwent surgery if the tumor was resectable.

RESULTS

Interim analysis was performed when 95 patients were included. The trial was stopped due to significantly better results in the control arm. Differences in response (P = .04) were favorable to CDDP-FU. Hematologic toxicity predominated in the CBDCA-FU arm (P < .001). Mucositis and vomiting predominated in the CDDP-FU arm (P = .03, P < .001, respectively). Favorable outcomes (complete response [CR] plus any grade of toxicity and PR plus grade 0 to 3 toxicity) predominated in the CDDP-FU arm (P = .02). Only the treatment assigned was associated with response (P = .02) and favorable outcomes (P = .009) in the logistic regression analysis. In the CDDP-FU arm, disease-free and overall survival were significantly better. Cox regression analysis showed that only treatment association with disease-free survival remains significant.

CONCLUSION

Our results indicate that CDDP-FU is more effective than CBDCA-FU as neoadjuvant treatment in stage IV-M0 head and neck cancer.
Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.
Authors: Santoro A , Tursz T , Mouridsen H , Verweij J , Steward W , Somers R , Buesa J , Casali P , Spooner D , Rankin E
Published: February 2017

PURPOSE

The aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas.

PATIENTS AND METHODS

This was a prospective randomized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer (EORTC). Six hundred sixty-three eligible patients were randomly allocated to receive either doxorubicin 75 mg/m2 (arm A), cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) (arm B), or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 (arm C).

RESULTS

The overall response rate was 24% (95% confidence interval, 20.7% to 27.3%) among eligible patients and 26% among assessable patients. No statistically significant difference was detected among the three study arms in terms of response rate (arm A, 23.3%; arm B, 28.4%; and arm C, 28.1%), remission duration (median, 46 weeks on arm A, 48 weeks on arm B, and 44 weeks on arm C), or overall survival (median, 52 weeks on arm A, 51 weeks on arm B, and 55 weeks on arm C). The degree of myelosuppression was significantly greater for the combination of ifosfamide and doxorubicin than for the other two regimens. Cardiotoxicity was also more frequent in this arm, but other toxicities were similar.

CONCLUSION

In advanced soft tissue sarcomas of adults, single-agent doxorubicin is still the standard chemotherapy against which more intensive or new drug treatments should be compared. Combination chemotherapy cannot be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen.
Contralateral breast cancer: annual incidence and risk parameters.
Authors: Broët P , de la Rochefordière A , Scholl S M , Fourquet A , Mosseri V , Durand J C , Pouillart P , Asselain B
Published: February 2017

PURPOSE

To screen for factors that might predict the risk of developing metachronous contralateral breast cancer (CBC), taking into account the influence of local or distant recurrence, and to assess the annual incidence of CBC.

PATIENTS AND METHODS

Of 4,748 women with invasive unilateral breast cancer, clinical stage I to IIIa, treated between 1981 and 1987, 282 metachronous CBCs were diagnosed. Due to competing risks between the occurrence of CBC and other events, several options for multivariate analysis were considered.

RESULTS

The median follow-up time was 80 months (range, 1 to 158). The cumulative rate of CBC was 4.1% +/- 0.3% at 5 years, and the annual incidence rate of CBC increased slowly, while the risk of local recurrence and metastases decreased after the fourth year. Whichever model we chose, age less than 55 years (relative risk [RR] = 1.40) at the time of diagnosis of the first breast cancer, as well as the presence of lobular type carcinoma (RR = 1.50), was associated with an increased risk of developing a tumor in the contralateral breast. Adjuvant chemotherapy significantly decreased (RR = 0.54) the risk of CBC.

CONCLUSION

Lobular histology and age less than 55 years are found to increase the risk of CBC, while adjuvant chemotherapy significantly decreased the risk of CBC. The progressive rise in the annual incidence rates of CBC, together with the absence of a link between clinical prognostic factors of the first cancer and CBC, suggested that CBC can be considered as a second primary breast cancer.
Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study.
Authors: McGuire W P , Hoskins W J , Brady M F , Homesley H D , Creasman W T , Berman M L , Ball H , Berek J S , Woodward J
Published: February 2017

PURPOSE

We report a prospective randomized trial in women with advanced ovarian cancer to evaluate the importance of chemotherapy dose-intensity on survival, progression-free survival (PFS), and response.

PATIENTS AND METHODS

A total of 485 patients with epithelial ovarian cancer and residual masses more than 1 cm following surgery (stage III presentation) or any stage IV presentation were randomly assigned to receive either standard therapy (cyclophosphamide 500 mg/m2 and cisplatin 50 mg/m2 intravenously every 3 weeks for eight courses) or intense therapy (cyclophosphamide 1,000 mg/m2 and cisplatin 100 mg/m2 intravenously every 3 weeks for four courses). Dose modification was rigidly controlled to maintain intensity. Clinical and pathologic responses were assessed, when appropriate, as well as PFS interval and survival.

RESULTS

A total of 458 patients met all eligibility criteria and were assessed for survival and PFS. The dose-intensive group received the same total dose of cyclophosphamide and cisplatin, but 1.97 times greater dose-intensity than the standard group. Clinical and pathologic response rates; response duration, and survival were similar in both groups of patients. Hematologic, gastrointestinal, febrile episodes, septic events, and renal toxicities were significantly more common and severe in the dose-intensive group.

CONCLUSION

A doubling of the dose-intensity in the treatment of bulky ovarian epithelial cancers led to no discernible improvement in patient outcome and was associated with more severe toxicity. This study provides no evidence to support the hypothesis that modest increases in dose-intensity without increasing total dose are associated with significant improvement in overall survival or PFS.
T-cell-rich B-cell lymphomas: diagnosis and response to therapy of 44 patients.
Authors: Greer J P , Macon W R , Lamar R E , Wolff S N , Stein R S , Flexner J M , Collins R D , Cousar J B
Published: February 2017

PURPOSE

Clinicopathologic features of 44 patients with well-documented T-cell-rich B-cell lymphomas (TCRBCLs) were reviewed to determine if there were distinguishing clinical characteristics and to evaluate the responsiveness to therapy.

PATIENTS AND METHODS

Forty-one patients had de novo TCRBCL, while three patients had a prior diagnosis of diffuse large B-cell lymphoma. Seventeen TCRBCLs were identified from a retrospective analysis of 176 lymphomas diagnosed before 1988 as peripheral T-cell lymphoma (PTCLs). The initial pathologic diagnosis was incorrect in 36 of 44 cases (82%), usually due to the absence of adequate immunophenotypic and/or genotypic studies at the initial study.

RESULTS

The median age of patients was 53 years (range, 17 to 92), and the male-to-female ratio was 1.4:1. B symptoms were present in 22 of 41 patients (54%); splenomegaly was detected in 11 patients (25%). Clinical stage at diagnosis was as follows: I (n = 8), II (n = 6), III (n = 15), IV (n = 14), and unstaged (n = 1). Although therapy was heterogeneous, the disease-free survival (DFS) and overall survival (OS) rates at 3 years for patients with de novo TCRBCL were 29% and 46%, respectively. A complete response (CR) to combination chemotherapy for intermediate-grade lymphomas was observed in 16 of 26 patients (62%); 11 of these patients (42%) had a continuous CR, compared with one of 14 patients (7%) who received radiation therapy or therapy for low-grade lymphoma or Hodgkin's disease (HD) (P < .05). However, there was no difference in OS between patients who received chemotherapy for intermediate-grade lymphoma versus other therapies (49% v 48%) due to a high response rate to salvage therapies, including seven patients without disease after marrow transplantation.

CONCLUSION

TCRBCLs are difficult to recognize without immunoperoxidase studies. Patients with TCRBCL have clinical features similar to patients with other large B-cell lymphomas, except they may have more splenomegaly and advanced-stage disease; they should receive combination chemotherapy directed at large-cell lymphomas.
Phase I clinical and pharmacokinetic study of topotecan administered by a 24-hour continuous infusion.
Authors: van Warmerdam L J , ten Bokkel Huinink W W , Rodenhuis S , Koier I , Davies B E , Rosing H , Maes R A , Beijnen J H
Published: February 2017

PURPOSE

To determine the maximum-tolerable dose (MTD) and to investigate the pharmacokinetics and pharmacodynamics of topotecan in a phase I study. Topotecan is a novel semisynthetic derivative of the anticancer agent camptothecin and inhibits the intranuclear enzyme topoisomerase I. Broad preclinical activity rationalized further clinical evaluation.

PATIENTS AND METHODS

In this phase I trial, topotecan was administered by 24-hour continuous infusion every 21 days to patients with solid malignant tumors.

RESULTS

A total of 25 eligible patients, of whom 22 were pretreated, entered the study. They received the following dosages of topotecan: 2.5, 3.75, 5.60, 8.4, and 10.5 mg/m2 by 24-hour infusion. Reversible leukopenia and thrombocytopenia were dose-limiting, with mild anemia occurring regularly. Other toxicities, such as alopecia, mucositis, nausea, and vomiting were sporadic and mild. Responses were not observed. However, eight patients had stable disease. The plasma concentration-time curves were not compatible with standard linear pharmacokinetic models, and indications were found for the occurrence of nonlinear (saturation) kinetics at the dosages studied.

CONCLUSION

The recommended dose for phase II studies is 8.4 mg/m2 when administered as a 24-hour infusion, which is well tolerated. Further studies will be necessary to account for the putative nonlinear behavior of the drug.
Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies.
Authors: Uziely B , Jeffers S , Isacson R , Kutsch K , Wei-Tsao D , Yehoshua Z , Libson E , Muggia F M , Gabizon A
Published: February 2017

PURPOSE

The purpose of our studies was to define the maximal-tolerated dose of liposomal doxorubicin (DOX-SL; Liposome Technology Inc, Menlo Park, CA), a doxorubicin formulation of polyethyleneglycol-coated liposomes, characterize the toxicities associated with this formulation, and evaluate any indication of antitumor activity within a phase I setting.

PATIENTS AND METHODS

Two separate phase I studies were conducted following the initial human pharmacokinetic testing at one of the sites (Hadassah). The starting dose of 20 mg/m2 at the University of Southern California was just below the dose without toxicity in the pharmacokinetic study. At Hadassah, the phase I starting dose was just above their earlier safe single doses, 60 mg/m2. Both studies involved cohorts of at least three patients and redosing every 3 to 4 weeks. To determine the recommended dose for phase II trials, an additional level of 50 mg/m2 every 3 weeks was explored, and the level of 60 mg/m2 every 4 weeks was expanded.

RESULTS

A total of 56 patients receiving 281 courses of DOX-SL was accrued and evaluated for toxicity. Hand-foot (H-F) syndrome and stomatitis are the two main dose-limiting factors of DOX-SL. Stomatitis was dose-limiting for high single doses of DOX-SL greater than 70 mg/m2. Skin toxicity manifested primarily as H-F syndrome was dose-limiting for repetitive dosing, but acceptable at either 50 mg/m2 every 3 weeks or 60 mg/m2 every 4 weeks. Attenuation of acute subjective symptoms and lack of alopecia were generally observed. Patients with carcinomas of the breast, ovary, prostate, and head and neck were among those showing objective antitumor responses or improvement based, in part, on blood levels of tumor markers.

CONCLUSION

The toxicity profile of DOX-SL differs prominently from that of the free drug administered by bolus or rapid infusion and with some differences, resembles that of prolonged continuous infusion. This finding, as well as the antitumor activity observed, supports wide phase II testing of DOX-SL in solid tumors.
Does knowledge guide practice? Another look at the management of non-small-cell lung cancer.
Authors: Raby B , Pater J , Mackillop W J
Published: February 2017

PURPOSE

To describe Canadian doctors' beliefs about the appropriate role of chemotherapy and radiotherapy in the management of non-small-cell lung cancer (NSCLC).

METHODS

A mail survey of a random sample of Canadian respirologists, thoracic surgeons, radiation oncologists, and medical oncologists was performed. Three cases of NSCLC were described and respondents were asked to estimate the prognosis in each case and to give their treatment recommendations.

RESULTS

Responses were obtained from 234 of 330 eligible subjects (74%). Doctors' treatment recommendations varied widely. After a complete resection for stage II NSCLC, 68% recommended no adjuvant treatment, 28% recommended radiotherapy, 1% recommended chemotherapy, and 3% recommended both radiotherapy and chemotherapy. For an asymptomatic patient with stage IIIb NSCLC, 17% recommended no active treatment, 65% recommended radiotherapy alone, 16% recommended radiation and chemotherapy, and 2% recommended chemotherapy alone. For an asymptomatic patient with a stage IV NSCLC, 80% recommended no active treatment and 20% recommended chemotherapy. Doctors' beliefs about the natural history of NSCLC and its response to treatment varied widely. Seventy-five percent of respondents believed that adjuvant radiotherapy did not increase survival in stage II disease, but 25% believed that it did. Thirty percent believed that the addition of chemotherapy to radiotherapy in stage III increased survival, but 70% believed that it did not. Fifty-five percent believed that chemotherapy increased the median survival in stage IV, but 45% believed that it did not. Doctors' beliefs about the efficacy of treatment were strongly associated with their treatment recommendations.

CONCLUSION

Personal beliefs, rather than universal knowledge, currently guide the management of NSCLC in Canada.
CD44 variant expression is a common feature of epithelial ovarian cancer: lack of association with standard prognostic factors.
Authors: Cannistra S A , Abu-Jawdeh G , Niloff J , Strobel T , Swanson L , Andersen J , Ottensmeier C
Published: February 2017

PURPOSE

CD44 is a hyaluronic acid receptor that exists as a standard 90-kd form (CD44S) as well as several CD44 variant isoforms produced through alternative splicing. Expression of CD44 variants is associated with clinically aggressive behavior in some human tumors. The purpose of the present study is to define the expression of CD44 variant isoforms in ovarian cancer and to investigate whether the expression of these molecules is associated with adverse prognosis.

MATERIALS AND METHODS

Six specimens of normal ovarian surface epithelium (NOSE) and 31 separate cases of newly diagnosed ovarian cancer were studied by a combination of reverse-transcription polymerase chain reaction (RT-PCR) and immunoperoxidase staining. Clinical correlation was made between CD44 variant expression and stage (I/II v III/IV), residual disease (< or = 2.0- v > 2.0-cm mass), age (< or = 65 v > 65 years), histology (papillary serous v other), grade, and survival.

RESULTS

RT-PCR analysis revealed that NOSE predominantly expressed transcripts for CD44S, as well as a restricted pattern of transcripts characteristic of CD44 splice variants. CD44S and CD44 variant exon nine sequences (CD44-9v) were focally expressed in one of two NOSE specimens examined by immunoperoxidase staining. In comparison, the majority (71%) of ovarian cancer specimens expressed a complex pattern of CD44 splice variants by RT-PCR analysis. Immunoperoxidase studies revealed that the majority of ovarian cancer specimens expressed both CD44S and CD44-9v, whereas expression of sequences from variant exons 3, 4, and 6 was uncommon. There was no association between CD44 variant expression (transcript or protein) and stage, residual disease, age, histology, grade, or survival.

CONCLUSION

Expression of CD44S and CD44-9v is a common feature of epithelial ovarian cancer cells. The lack of a significant association between CD44 variant expression and prognosis suggests that other factors may be more important in determining the clinical behavior of this disease.
Phase I and pharmacologic studies of pyrazoloacridine, a novel DNA intercalating agent, on single-dosing and multiple-dosing schedules.
Authors: Rowinsky E K , Noe D A , Grochow L B , Sartorious S E , Bowling M K , Chen T L , Lubejko B G , Kaufmann S H , Donehower R C
Published: February 2017

PURPOSE

To determine the maximum-tolerated doses (MTDs), principal toxicities, and pharmacologic behavior of pyrazoloacridine (PZA), a novel DNA intercalator with a unique mechanism of action, on single- and multiple-dosing schedules.

PATIENTS AND METHODS

PZA was administered on a single-dosing schedule as a 1- to 3-hour infusion and on a multiple-dosing schedule as a 1-hour infusion daily for 5 days to cancer patients at doses ranging from 400 to 935 mg/m2 and 40 to 180 mg/m2/d every 3 weeks, respectively.

RESULTS

On the single-dosing 1-hour schedule, CNS toxicity, characterized by neuropsychiatric and neuromotor effects, prompted prolongation of the infusion duration to 3 hours and led to a study of PZA on a multiple-dosing schedule. Both measures resulted in lower incidence of CNS toxicity. Neutropenia was the principal toxicity and precluded dose escalation to levels greater than 750 mg/m2 on the single-dosing (3-hour) schedule and 150 mg/m2/d x 5 (total dose, 750 mg/m2) on the multiple-dosing schedule. Thrombocytopenia, anemia, and nonhematologic effects occurred less frequently. Responses were observed in several patients with platinum- and taxane-refractory ovarian carcinoma; antitumor activity was also noted in patients with cervical and colorectal carcinomas. Significant intraindividual variability characterized by the presence of multiple drug peaks and troughs was observed in the pharmacologic studies. The maximal PZA concentrations achieved in both studies exceeded drug concentrations associated with significant cytotoxicity in preclinical studies and correlated with the occurrence of CNS toxicity.

CONCLUSION

Neutropenia is the dose-limiting toxicity on both schedules and 750 mg/m2 and 150 mg/m2/d are the recommended starting doses of PZA on single- and multiple-dosing schedules, respectively, for minimally pretreated patients in phase II studies; slightly lower doses are recommended for more heavily pretreated subjects. The favorable toxicity profile of PZA and its antitumor activity in several refractory tumors warrant broad phase II evaluations of this agent.
Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin.
Authors: Abbruzzese J L , Abbruzzese M C , Lenzi R , Hess K R , Raber M N
Published: February 2017

PURPOSE

Diagnostic strategies designed to identify the underlying primary malignancies in patients with unknown primary tumors (UPTs) have relied on retrospective analyses. We analyzed 879 consecutive patients referred with suspected UPTs to determine the yield and cost of a limited diagnostic evaluation, assess the contribution of specific studies to diagnosis, and analyze the survival patterns of patients in whom the primary tumor was diagnosed.

PATIENTS AND METHODS

Data from patients with a suspected UPT were entered into a computerized data base, and the patients underwent a predefined limited diagnostic evaluation. Primary malignancies were diagnosed by pathologic review alone or by pathologic criteria plus a physical or radiographic finding. Survival was measured from diagnosis, estimated using the Kaplan-Meier method, and compared using the Cox-Mantel log-rank test.

RESULTS

A primary tumor was found in 179 of 879 patients (20%). The survival duration of patients in whom the primary tumor was diagnosed was superior to that of patients in whom the primary tumor remained unknown. Specific patient subsets contributed most to the improved survival duration of the group in which the primary tumor was found, including lymphoma patients diagnosed solely by pathologic criteria and female patients with primary breast or ovarian cancer. The cost of diagnosis was mostly due to the extensive use of computed tomography. Except for ovarian cancer, computed tomography rarely identified treatable primary tumors.

CONCLUSION

The limited diagnostic evaluation used in this study identified patients with treatable malignancies and increased the survival duration of a population of suspected UPT patients. Primary malignancies with the best survival can be diagnosed through careful pathologic review and focused evaluations for breast and ovarian cancer in women.
Biology and therapy of pediatric rhabdomyosarcoma.
Authors: Pappo A S , Shapiro D N , Crist W M , Maurer H M
Published: February 2017

PURPOSE

To review key developments in biology and therapy of rhabdomyosarcoma (RMS) since the early 1970s.

PATIENTS AND METHODS

The literature regarding biology, therapy, and late effects of therapy through March 1995 was reviewed.

RESULTS

The two major histiotypes, embryonal and alveolar, are characterized by specific genetic abnormalities that provide clues to mechanisms of tumor induction. Alveolar tumors, for example, often possess a chromosomal translocation [t(2;13)(q35;q14)] that fuses the PAX3 gene in band 2q35 with the FKHR gene in band 13q14, creating a novel chimeric protein that could inappropriately activate normal targets of the PAX3 gene product, thereby contributing to tumorigenesis. Recognition of prognostically important patient groups primarily identified by tumor extent, site, and histology, and development of effective risk-based multimodal therapy in randomized trials, have increased long-term survival in RMS from 25% in 1970 to more than 70% in current studies. The most significant recent gain in therapeutic results was realized in patients with gross residual tumor after biopsy.

CONCLUSION

Contemporary risk-based therapy cures more than two thirds of children with RMS while minimizing acute and late effects. Increased dose-intensity of known effective agents with hematopoietic growth factor support, new agents, and hyperfractionated irradiation are being evaluated in hopes of further improving therapy. Recent discovery of novel genetic features in this tumor should lead to better methods of diagnosis and risk assessment, and ultimately to identification of molecular targets for specific treatment.
An institutional commitment to pain management.
Authors: Ferrell B R , Dean G E , Grant M , Coluzzi P
Published: February 2017

PURPOSE

To share the development, implementation, and evaluation of a program called "An Institutional Commitment to Pain Management," which is based on the philosophy of organizational influence on pain management.

METHODS

A tested pain education model was disseminated to 32 physician/nurse teams in settings throughout California, after which the 64 professionals returned to their institutions to serve as role models and catalysts to change the practice of pain management. Each team member completed a 39-item survey about knowledge and attitudes related to pain, which was developed by B.R.F. and colleagues, and also identified three goals for the implementation of course information. Precourse data also included administration of the knowledge and attitudes survey to participating physicians' and nurses' colleagues (10 physicians and 20 nurses per institution). Each team completed five chart audits using the pain audit tool (PAT), which was developed by B.R.F. and colleagues at the City of Hope National Medical Center. The PAT identifies how pain is managed currently at the institutional level. Final course evaluation 8 months after course completion included a summary of activities implemented by the teams as well as the factors that served as barriers and benefits to improve the quality of pain management.

RESULTS

Two hundred seventy-two physicians and 629 nurses completed the survey about knowledge and attitudes related to pain, and 154 PATs were submitted. These results, as well as evaluation at the completion of the course, are discussed.

CONCLUSION

The Institutional Commitment to Pain Management program is an evolving model that was developed to overcome barriers to pain relief by obtaining the commitment from institutions to improve the management of pain for their patients.
Phase I study of paclitaxel and topotecan in patients with advanced tumors: a cancer and leukemia group B study.
Authors: Lilenbaum R C , Ratain M J , Miller A A , Hargis J B , Hollis D R , Rosner G L , O'Brien S M , Brewster L , Green M R , Schilsky R L
Published: February 2017

PURPOSE

To define the dose-limiting toxicities (DLTs) and the recommended phase II doses of paclitaxel combined with topotecan, without and with filgrastim support.

PATIENTS AND METHODS

Patients with advanced solid tumors and a maximum of one prior chemotherapy regimen for metastatic disease were eligible if they had a performance status of 0 to 1 and normal renal, hepatic, and bone marrow function. Prior treatment with taxanes or comptothecin analogs, and prior pelvic irradiation were not allowed. Patients with a history of cardiac disease or on medications known to affect cardiac conduction were excluded. The dose of topotecan was fixed at 1.0 mg/m2/d for 5 days. The dose of paclitaxel was escalated until the maximum-tolerated dose (MTD), without and with filgrastim 5 micrograms/kg subcutaneously (SC) on days 6 to 14, was reached. Paclitaxel was administered over 3 hours on day 1 before topotecan. Treatment cycles were repeated every 21 days.

RESULTS

Of 46 patients entered, 45 were assessable for toxicity and 34 for response. The principal toxicity was neutropenia. Without filgrastim, the MTD of paclitaxel was 80 mg/m2 on day 1 in combination with topotecan 1.0 mg/m2/d for 5 days. With filgrastim, the dose of paclitaxel was escalated to 230 mg/m2 in combination with the same dose of topotecan. At this dose level, one patient had hematologic DLT and a second patient developed neuromuscular DLT. Three patients had a partial response (PR): one with head and neck cancer, a second with non-small-cell lung cancer, and the third with colon cancer.

CONCLUSION

We conclude that paclitaxel can be given at clinically relevant doses in combination with topotecan and filgrastim. The recommended dose for phase II studies is paclitaxel 230 mg/m2 on day 1 and topotecan 1.0 mg/m2/day for 5 days with filgrastim 5 micrograms/kg on days 6 to 14.
Biphasic patterns of memory deficits following moderate-dose partial-brain irradiation: neuropsychologic outcome and proposed mechanisms.
Authors: Armstrong C , Ruffer J , Corn B , DeVries K , Mollman J
Published: February 2017

PURPOSE

To identify the longitudinal neurobehavioral characteristics of the early-delayed and late-delayed effects of partial-brain radiotherapy for patients with supratentorial brain tumors with favorable histology. This study improves on previous attempts to identify radiation effects, because of the inclusion of baseline measures and the use of subjects as their own controls.

PATIENTS AND METHODS

Ten neuropsychologic domains were measured in 12 patients at baseline (post-surgery and immediately before initiation of radiotherapy), and followed trimonthly for 1 year. Four to six patients were examined at 2 and 3 years postbaseline.

RESULTS

Patients were impaired at baseline compared with controls only in visual memory and sentence recall, but demonstrated significant improvement in visual memory by 2 years postbaseline. Speed of processing information also showed a slope of improvement over 2 years. Retrieval from verbal long-term memory was impaired at 1.5 months postcompletion of radiotherapy, but recovered to baseline levels by 1 year. At 2 years postbaseline, long-term memory retrieval demonstrated a decline, but remained unchanged at 3 years.

CONCLUSION

Long-term memory appears to be sensitive to the effects of radiotherapy. We confirmed our previous findings of a decrement with rebound during the early-delayed period, and propose that these findings are consistent with demyelination/remyelination. Decrement was observed again at 2 years postbaseline, which suggests that memory retrieval may be the earliest marker of late-delayed effects. These neurocognitive patterns are consistent with leukoencephalopathy. Confirmation of these observations will be possible if neuropsychologic testing with the same sensitivity can be incorporated into national collaborative trials.
Escalated MVAC with or without recombinant human granulocyte-macrophage colony-stimulating factor for the initial treatment of advanced malignant urothelial tumors: results of a randomized trial.
Authors: Logothetis C J , Finn L D , Smith T , Kilbourn R G , Ellerhorst J A , Zukiwski A A , Sella A , Tu S M , Amato R J
Published: February 2017

PURPOSE

Hematopoietic growth factors have been shown to ameliorate the side effects of chemotherapy. Here we assess the ability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to increase the dose-intensity and reduce the side effects of escalated methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy.

PATIENTS AND METHODS

A prospective randomized trial to compare escalated MVAC versus escalated MVAC with rhGM-CSF was conducted. All patients were treated at The University of Texas M.D. Anderson Cancer Center (UTMDACC) and had a metastatic or unresectable urothelial tumor. Forty-eight patients were randomized (25 to MVAC with rhGM-CSF and 23 to escalated MVAC alone). The clinical characteristics of the study populations were similar (ie, degree of tumor dissemination and performance status).

RESULTS

The dose-intensity in the two arms of the study did not differ significantly. No difference in the frequency of bacteriologically documented infections occurred between the two study arms.

CONCLUSION

The use of the hematopoietic growth factor rhGM-CSF did not result in an increased dose-intensity of escalated MVAC. The inability to increase the dose-intensity of MVAC further was a result of nonhematologic side effects of the chemotherapy. Escalation of treatment delivered at its median-tolerated dose is unlikely to result in additional therapeutic benefit for patients with common solid tumors. Future development of therapy may require the development of new agents or concepts, rather than modification of existing therapies.
Controlled clinical trial of interferon-gamma as postoperative surgical adjuvant therapy for colon cancer.
Authors: Wiesenfeld M , O'Connell M J , Wieand H S , Gonchoroff N J , Donohue J H , Fitzgibbons R J , Krook J E , Mailliard J A , Gerstner J B , Pazdur R
Published: February 2017

PURPOSE

The primary goal of this study was to assess the effectiveness of interferon gamma (IFN-gamma) to prevent tumor relapse following potentially curative surgery in patients with high-risk colon cancer. A secondary goal was to determine the effect of IFN-gamma on immune function and to correlate alterations in immune parameters with survival.

PATIENTS AND METHODS

Three to 4 weeks after undergoing resection of all known malignant disease, 99 patients with stage II, III, or IV colon cancer were randomly assigned to receive IFN-gamma 0.2 mg total dose by subcutaneous injection daily for 6 months or observation. Serial assessment of human leukocyte antigen (HLA)-DR expression and Fc receptors on peripheral-blood monocytes was conducted in 24 patients who received IFN-gamma and 27 control patients.

RESULTS

With a median follow-up duration of 59 months in patients still alive, there was evidence of a detrimental effect on time to relapse (P = .03) among patients who received IFN-gamma. There was no significant difference in patient survival (P = .12). This study has sufficient power to rule out a 25% reduction in death rate for patients who received IFN-gamma (P < .05). Significant enhancement of immune function was observed in patients treated with IFN-gamma as measured by HLA-DR expression (P < .01) and Fc receptors (P < .001) on peripheral-blood monocytes.

CONCLUSION

This study effectively rules out any clinically meaningful benefit for IFN-gamma as surgical adjuvant treatment for patients with high-risk colon cancer. Although significant enhancement of nonspecific immune function was seen with this dosage administration schedule of IFN-gamma, this was not associated with any demonstrable antitumor effect.
Surgical treatment of spinal cord compression from epidural metastasis.
Authors: Sundaresan N , Sachdev V P , Holland J F , Moore F , Sung M , Paciucci P A , Wu L T , Kelligher K , Hough L
Published: February 2017

PURPOSE

A retrospective study of the results of neoplastic cord compression was undertaken to determine the effectiveness of surgical treatment and to assess quality of life in patients undergoing extensive procedures with potential morbidity.

PATIENTS AND METHODS

Over a 5-year period (1989 to 1993), a total of 110 patients underwent surgery. Fifty-five patients (50%) had undergone prior treatment, including 47 (43%) who had failed to respond to prior irradiation (RT). Before surgery, 48 patients (44%) were nonambulatory, with severe paresis being present in 20. Surgery included staged anterior-posterior resections in 53 patients (48%), anterior resections in 33 (30%), and posterior resection in six (5%), all of whom required spinal instrumentation for reconstruction; only 18 patients underwent resection without instrumentation.

RESULTS

Postoperatively, 90 patients (82%) were improved, both in terms of pain relief and ambulatory status. Fifty-three patients (48%) experienced postoperative complications, related statistically to the following three factors: age over 65 years, prior treatment, and presence of paraparesis. The overall median survival duration was 16 months, with 46% alive at 2 years. Apart from primary tumor, the presence of preoperative paraparesis had the most significant impact on survival.

CONCLUSION

Our data suggest that the effective surgical treatment of neoplastic compression requires anterior-posterior resection in most patients to achieve the goal of total tumor resection, with the majority requiring instrumentation. Long-term survival is feasible in a subset of patients with this aggressive surgical approach.
Role of surgical resection in pelvic Ewing's sarcoma.
Authors: Scully S P , Temple H T , O'Keefe R J , Scarborough M T , Mankin H J , Gebhardt M C
Published: February 2017

PURPOSE

The improved survival in patients with Ewing's sarcoma over the past two decades has placed increased importance on achievement of local disease control. Ewing's sarcoma that arises in the pelvis has been recognized to have a worse prognosis than that in the appendicular skeleton, and the role of surgical resection in these cases remains controversial. The current study attempts to identify a benefit to surgical resection in these patients.

METHODS

We retrospectively examined 39 patients who presented with Ewing's sarcoma in a pelvic location, all of whom were treated systemically with chemotherapy. Twenty patients received radiation only as a means of local control, and 19 underwent resection with or without radiation therapy. The patients were evaluated with end points of disease-free survival and overall survival for a minimum of 24 months and a mean of 58 months.

RESULTS

There was an even distribution among patients who underwent surgical resection for local control as compared with those who received only radiation therapy with respect to age, site, date of treatment, and stage of disease. Despite uncontrolled biases including tumor size and response to chemotherapy that would be expected to favor patients who undergo resection, surgery in addition to or in substitution for radiation therapy did not result in a statistically significant increase in disease-free survival or overall survival. Local disease control was comparable between those who underwent resection and those who did not: three patients in each group developed a local recurrence.

CONCLUSION

Currently, morbidity of surgical resection should be weighed against the efficacy and secondary complications of radiation therapy in the decision-making process for local disease control. The issue of whether overall survival and local disease control is improved in patients who undergo surgical resection remains controversial and may require a prospective randomized trial to be answered definitively.
Patient participation in clinical decision-making for treatment of T3 laryngeal cancer: a comparison of state and process utilities.
Authors: van der Donk J , Levendag P C , Kuijpers A J , Roest F H , Habbema J D , Meeuwis C A , Schmitz P I
Published: February 2017

PURPOSE

To study the use of two different approaches, and feasibility of four commonly used utility assessment methods to assess preferences for treatment of T3-laryngeal cancer by surgery or radiation therapy (RT).

METHODS

Utility assessment methods, namely, time trade-off (TTO), standard reference gamble (SRG), rating scale (RS), and direct comparison (DC), were used to assess utilities in two groups of former cancer patients (n = 10 for both), a group of clinicians (n = 9), and a group from the general population (n = 10). For the treatment modalities, ie, surgery and RT, two types of scenarios were developed and used: the state scenario, which describes a stable health state after treatment, and the process scenario, which describes a dynamic process. First, utilities were assessed based on state scenarios. Next, respondents were thoroughly informed and educated with respect to the relevant aspects of both treatment modalities. Subsequently, utilities were again assessed, but now based on the process scenarios. The outcome of each approach was calculated and expressed in a quality-adjusted life-expectancy (QALE) score for each treatment modality, and the treatment with the highest outcome was said to be the preferred treatment modality.

RESULTS

In general, a higher QALE score for each treatment modality was found for clinicians and for the general population as compared with the former-cancer-patient groups. When the outcome of both approaches was compared on an individual level dependent on the utility assessment method, 32% to 43% of respondents showed an inconsistent treatment preference.

CONCLUSION

The approach to assess utilities and the extent to which respondents are informed about treatment modalities have a major effect on individual treatment preferences.
Immune-mediated and unusual complications during interferon alfa therapy in chronic myelogenous leukemia.
Authors: Sacchi S , Kantarjian H , O'Brien S , Cohen P R , Pierce S , Talpaz M
Published: February 2017

PURPOSE

Long-term treatment with interferon alfa (IFN alpha) can produce or exacerbate immune-mediated complications (IMC). The purpose of this study was to analyze the experience with IMC and unusual complications in patients with chronic myelogenous leukemia (CML) undergoing IFN alpha treatment.

PATIENTS AND METHODS

The occurrence of IMC and unusual complications was evaluated in patients with Philadelphia chromosome (Ph)-positive CML.

RESULTS

Well-documented and clinically evident complications developed in 35 patients after a median of 14 months of IFN alpha treatment. These included 28 (5%) of 581 patients with Ph-positive CML treated with IFN alpha-containing regimens at M.D. Anderson Cancer Center (MDACC) and seven patients referred for opinion or problems who were on other studies. Hypothyroidism occurred in 11 patients (2%), immune-mediated hemolysis in seven (1%), and connective tissue diseases in 11 (2%). Other unusual occurrences included congestive heart failure (CHF; n = 4), porphyria cutanea tarda (PCT; n = 3), membranous glomerulonephritis (MGN; n = 1), and vitiligo (n = 1). IFN treatment was discontinued in 19 patients and the dose was reduced in five. Ten of 11 patients (91%) with immune-mediated hypothyroidism and eight of 11 (73%) with connective tissue diseases had some degree of cytogenetic response at the time of the event.

CONCLUSION

Although the frequency of IMC is low, patients treated with IFN alpha should be monitored for signs and symptoms of autoimmunity.
Role of image-guided core-needle biopsy in the management of patients with lymphoma.
Authors: Pappa V I , Hussain H K , Reznek R H , Whelan J , Norton A J , Wilson A M , Love S , Lister T A , Rohatiner A Z
Published: February 2017

PURPOSE

The results of 106 radiologically guided core needle biopsies in 96 patients were analyzed retrospectively to evaluate the accuracy, safety, and role of this technique in the management of patients with lymphoma and to determine factors predictive of success.

PATIENTS AND METHODS

Biopsies were performed in 51 patients with low-grade non-Hodgkin's lymphoma (NHL), 24 with high-grade NHL, 16 with previously diagnosed Hodgkin's disease (HD), and 15 with no previous history of lymphoma. Disease was infradiaphragmatic in 92 patients and supradiaphragmatic in 14. Computed tomography (CT) guidance was used in 98 biopsies and ultrasonography (US) in eight.

RESULTS

The biopsy was diagnostic and yielded information on the basis of which treatment was started in 88 of 106 patients. The procedure was well tolerated and there were no major complications. Small size of the sample or inappropriate tissue sampled were the main causes of failure. The technique was equally successful in the diagnosis of HD and both high-grade and low-grade NHL as in nonlymphoproliferative disorders. The procedure was equally successful at diagnosis as at suspected recurrence or progression. In 33 of 80 cases in which the biopsy was performed at the time of recurrence or progression, the histology had changed; in 31 of 33, this influenced treatment. The technique was efficient at diagnosing transformation of follicular NHL in 16 of 18 patients, which allowed early adjustment of treatment at recurrence.

CONCLUSION

At St Bartholomew's Hospital (SBH), image-guided core-needle biopsy has proven to be a quick, safe, and efficient alternative to excisional biopsy in the evaluation of lymphoproliferative disorders at presentation, recurrence, or progression. It should become the procedure of choice for histologic sampling in the absence of peripheral lymphadenopathy.