bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of irradiated heart volumes in stage I breast cancer patients treated with postoperative adjuvant radiotherapy.
Authors: Gyenes G , Gagliardi G , Lax I , Fornander T , Rutqvist L E
Published: February 2017

PURPOSE

To quantify the proportion of heart volumes that received at least 25 Gy with tangential photon fields in patients with left-sided stage I (T1 NOMO) breast cancer treated with breast-conserving surgery.

METHODS AND MATERIALS

The dose planning of 100 consecutive patients was reviewed. All were irradiated with tangential photon fields that covered the left breast only. A three-dimensional computed tomographic (CT)-based dose planning was made for each patient. The prescribed dose to the tumor was 50 Gy. For each patient, the proportion of the heart included in the 50% isodose was determined from the cumulative dose-volume histogram (DVH). The same volume determination was made for the left-sided breast cancer patients treated with tangential fields during the first Stockholm Breast Cancer Trial.

RESULTS

The mean irradiated heart volume that received at least 25 Gy was 5.7% (SD = 4.5%) for the whole group and 11.9% (SD = 3.7%) in those with the highest volumes. The mean irradiated heart volume included in the 50% isodose for patients in the Stockholm Trial was 25% (SD = 11.9%).

CONCLUSION

In this study, the majority of patients with left-sided T1NOMO breast cancer did not receive irradiation to substantial heart volumes. However, in 6% of all studied patients, the proportion of irradiated heart volume was close to the irradiated heart volumes with one of the treatment techniques used in the Stockholm Trial for patients with left-sided tumors. That technique has been associated with significantly increased cardiac mortality during long-term follow-up evaluation in a previous study. The CT-based three-dimensional treatment-planning system (TMS) represents a valuable tool in identifying such patients; thus, treatment may be conformed to reduce the irradiated heart volume.
Effectiveness of adjuvant chemotherapy in combination with tamoxifen for node-positive postmenopausal breast cancer patients.
Authors:   International Breast Cancer Study Group
Published: February 2017

PURPOSE

Adjuvant tamoxifen has been shown to reduce relapse and mortality among node-positive post-menopausal breast cancer patients. The value of adding chemotherapy to tamoxifen is controversial.

PATIENTS AND METHODS

Between July 1986 and April 1993, 1,266 postmenopausal breast cancer patients with node-positive disease were randomly assigned to receive one of four adjuvant therapy regimens: (A) tamoxifen alone for 5 years; (B) tamoxifen plus three courses of early cyclophosphamide, methotrexate, and fluorouracil (CMF) on months 1, 2, and 3; (C) tamoxifen plus delayed single courses of CMF on months 9, 12, and 15; (D) tamoxifen plus early and delayed CMF on months 1, 2, 3, 9, 12, and 15. The two-by-two factorial design allowed two direct comparisons: early CMF (B and D) versus no early CMF (A and C), and delayed CMF (C and D) versus no delayed CMF (A and B). Estrogen receptor (ER) status was known for all patients and was used to stratify the randomization. A total of 1, 212 patients (96%) were eligible and assessable. The median follow-up duration was 60 months.

RESULTS

The results of the two-by-two factorial comparisons were as follows: (1) early CMF added to tamoxifen significantly improved 5-year disease-free survival (DFS; 64% v 57%; hazards ratio [HR], 0.79; 95% confidence interval [CI], 0.66 to 0.95; P = .01); and (2) delayed CMF added to tamoxifen did not improve DFS (5-year DFS, 61% v 60%; HR, 0.97; 95% CI, 0.81 to 1.17; P = .77). For patients with ER-positive tumors, the addition of CMF, either early or delayed or both, reduced the relative risk of relapse by 22% to 36%. In contrast, for patients with ER-negative tumors, tamoxifen with delayed CMF was associated with a nonsignificant increased risk of relapse (HR, 1.27; 95% CI, 0.92 to 1.76; P = .15).

CONCLUSION

Postmenopausal patients with node-positive breast cancer should be offered combination chemotherapy in addition to tamoxifen. Tamoxifen should not be initiated before CMF, as this might be detrimental, especially for patients with ER-negative tumors.
Measuring standards of care for early breast cancer in an insured population.
Authors: Hillner B E , McDonald M K , Penberthy L , Desch C E , Smith T J , Maddux P , Glasheen W P , Retchin S M
Published: February 2017

PURPOSE

To demonstrate the use of a combined data base to evaluate the care for local/regional invasive breast cancer in a large insured population of women aged less than 64 years.

PATIENTS AND METHODS

We linked the procedural and hospital claims from Blue Cross Blue Shield (BCBS) of Virginia with clinical stage data from the Virginia Cancer Registry (VCR) from 1989 to 1991. A total of 918 women were assessed with a median age of 50 years; 68% had tumors less than 2 cm, 30% had positive axillary nodes, and 68% were assessed as having local summary stage. A quality-of-care "report card" was used based on standards of care from international Consensus Conferences.

RESULTS

Eight percent had a mastectomy as the initial biopsy procedure. Sixty-nine percent of women ultimately underwent mastectomy. Of those women who underwent lumpectomy, 86% had subsequent radiation. Within 3 months of diagnosis, 43% had a bone scan and 20% a computed tomography (CT) scan. Of women with positive axillary lymph nodes, 83% aged less than 51 years and 52% aged 51 to 64 years received chemotherapy. Fifty-six percent of all women had claims from a medical oncologist. Of women having a total mastectomy, 27% had claims from a plastic surgeon. Sixty-six percent to 76% of women had a mammogram, 24% a bone scan, and 14% a CT scan in the 0-18 and 18-36 month intervals following primary treatment.

CONCLUSION

This study confirms the feasibility of linking sources of data that provide complementary information needed to develop measurements regarding standards of quality and efficiency of oncologic care. This report should serve as an initial benchmark while we await reports from other populations to define the best practice.
Endoscopic ultrasound-guided real-time fine-needle aspiration biopsy of the pancreas in cancer patients with pancreatic lesions.
Authors: Faigel D O , Ginsberg G G , Bentz J S , Gupta P K , Smith D B , Kochman M L
Published: February 2017

BACKGROUND

Endoscopic ultrasound (EUS) is an important new tool in the staging of pancreatic malignancies. Using new curved linear-array instruments, real-time fine-needle aspiration biopsy (RTFNA) of pancreatic lesions can be performed.

METHODS

Forty-five patients with pancreatic lesions (22 males and 23 females) underwent staging with the Olympus EUM-20 (Olympus America Corp, Melville, NY) followed by EUS-RTFNA with the Pentax FG-32PUA (Pentax-Precision Instrument Corp, Orangeburg, NY) and the 22-gauge GIP needle (GIP Medizin Technik, Grassau, Germany).

RESULTS

EUS tumor stages were as follows: TO, n = 1; T1, n = 8; T2, n = 9; and T3 n = 27. Aspiration attempts were unsuccessful in four patients (two technical failures and two inadequate specimens). The remaining 41 lesions (mean size, 3.3 cm) were aspirated under EUS guidance (median passes, three) and the cytologic diagnoses were 25 definite adenocarcinoma, five suspicious for adenocarcinoma (three subsequently confirmed and two clinical course consistent with adenocarcinoma), and 11 negative for malignancy. Of 11 negatives, two were found to have adenocarcinoma, seven were confirmed benign at surgery (four cystadenomas and three inflammatory), one had a benign pseudocyst, and one had abundant inflammatory cells on RTFNA and follow-up time greater than 12 months with computed tomographic (CT) scans consistent with resolving inflammation. There were no false-positive RTFNAs. There were no procedure-related complications. Among those with diagnostic EUS-RTFNA (91%), the sensitivity for malignancy (confirmed plus suspicious) was 94% and negative predictive value 82%.

CONCLUSION

EUS-guided RTFNA is a safe and accurate method for performing pancreatic biopsy. It should be considered in patients with suspected pancreatic malignancies in whom a tissue diagnosis is required or when other modalities have failed. EUS-RTFNA allows for local staging and tissue diagnosis in one procedure.
Secondary acute myelogenous leukemia following safe exposure to etoposide.
Authors: Stine K C , Saylors R L , Sawyer J R , Becton D L
Published: February 2017

PURPOSE

To present two patients as illustrations of the risk of developing secondary acute myelogenous leukemia (sAML) when theoretically safe doses of etoposide (VP-16) are used.

PATIENTS AND METHODS

Patient no. 1 was a 15-year-old white girl diagnosed with stage IIa Hodgkin's disease. She was treated with a combination of vincristine, doxorubicin, bleomycin, and VP-16 (2 g/m2 total) over 4 months, followed by 25.5 Gy of involved-field radiotherapy. Patient no. 2 was an 11-year-old white boy diagnosed with virus-associated hemophagocytic syndrome (VAHS). He was treated with VP-16 intravenously (IV) and orally (0.3 g and 2.8 g/m2, respectively).

RESULTS

Patient no. 1 developed AML 16 months from the diagnosis of Hodgkin's disease. Patient no. 2 developed AML 26 months from diagnosis. Both bone marrows were consistent with French-American-British (FAB) M4 disease. Both patients had abnormalities of the long arm of chromosome 11.

CONCLUSION

The use of low-dose or oral VP-16 can be associated with the development of sAML. Clinicians should be cautious in the use of VP-16 in low-risk diseases.
Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group.
Authors: Connors J M , Klimo P , Adams G , Burns B F , Cooper I , Meyer R M , O'Reilly S E , Pater J , Quirt I , Sadura A , Shustik C , Skillings J , Sutcliffe S , Verma S , Yoshida S , Zee B
Published: February 2017

PURPOSE

This randomized, prospective trial compares outcomes for patients with advanced Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, and vinblastine (ABV) hybrid regimen or alternating MOPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

METHODS

Three hundred one patients with advanced Hodgkin's disease were randomized to receive MOPP/ ABV hybrid regimen or alternating MOPP/ABVD after stratification for prior treatment, B symptoms, and treatment center. Eligible patients were either previously untreated and found to have stage IIIB, IVA, or IVB disease or previously treated with wide-field irradiation. Responding patients received a minimum of eight cycles of chemotherapy. Those with residual disease in a localized region received irradiation between the sixth and seventh cycle of treatment.

RESULTS

Response rates to the two regimens were similar. Five-year overall survival rates were 81% and 83% for MOPP/ABV hybrid and alternating MOPP/ ABVD, respectively (P = .74; 95% confidence interval [CI] for the difference, -11% to 7%). Five-year failure-free survivals were 71% and 67% for MOPP/ABV hybrid and alternating MOPP/ABVD, respectively (P = .87; 95% CI for the difference, -9% to 17%). Significantly more episodes of febrile neutropenia and stomatitis were observed with the MOPP/ABV hybrid regimen; there was no significant difference in fatal toxicity. Patients with predefined, high-quality partial responses (PR-1s) had results similar to those with complete responses (CRs). Planned subset analysis showed no significant difference in outcome between the two arms of the trial for patients with newly diagnosed disease (5-year failure-free survival rates were 70% for MOPP/ABV hybrid and 59% for alternating MOPP/ABVD; P = .180), but superiority of alternating MOPP/ABVD for patients with prior irradiation (5-year failure-free survival 94% v 73%; P = .017).

CONCLUSION

MOPP/ABV hybrid and alternating MOPP/ABVD regimens are equally effective for patients with advanced Hodgkin's disease.
Patient preferences for interferon alfa in multiple myeloma.
Authors: Ludwig H , Fritz E , Neuda J , Durie B G
Published: February 2017

PURPOSE

Interferon alfa treatment in multiple myeloma marginally improves relapse-free and overall survival. Often it does so at the expense of toxicity and financial cost. If patients are unwilling or unable to participate in the decision of whether to initiate such treatment, known patient preferences can serve as guidelines for the physician. We interviewed myeloma patients in the United States to obtain information that might facilitate medical decision-making.

PATIENTS AND METHODS

Three hundred fifty-five myeloma patients throughout the United States were interviewed by telephone. Without identifying interferon alfa as the treatment agent, interviewers described potential adverse effects, financial cost, and self-injection procedures. The potential benefits of four treatment choices, derived from a meta-analysis of published data, were presented as gains in remission rate (+10%), remission duration (an additional 4 and 7 months, respectively, for induction and maintenance treatment), and overall survival (an additional 3 and 6 months, respectively, for induction and maintenance treatment). Patients' choices for or against use of the unidentified substance were recorded, and interferon was subsequently disclosed as the treatment. The profiles of patients making different choices were determined using multivariate regression techniques.

RESULTS

Approximately half of the patients accepted the unidentified treatment if remission and/or survival improved by at least 6 months. Accepters were younger and more likely to have used interferon. Of patients who rejected the unidentified treatment, 25% to 50% would have been willing to accept it if the benefits were > or = 12 months. Test/retest reliability of all choices, determined in 36 cancer patients, was 0.896.

CONCLUSION

In multiple myeloma, interferon therapy and, by inference, other treatments with comparable features are acceptable to approximately half of the patients if a 6-month gain in relapse-free or overall survival can be expected.
Endoscopic ultrasound in the evaluation of gastric small lymphocytic mucosa-associated lymphoid tumors.
Authors: Pavlick A C , Gerdes H , Portlock C S
Published: February 2017

PURPOSE

Low-grade, small lymphocytic lymphomas of the mucosa-associated lymphoid tissue (MALT) have recently been shown to be associated with Helicobacter pylori infections. Regression of these tumors has been reported with antibiotic therapy. Here we evaluate endoscopic ultrasound (EUS) as on objective method to evaluate pretreatment disease and posttherapy response.

MATERIALS AND METHODS

We retrospectively reviewed 20 patients initially diagnosed elsewhere with MALT lymphoma. All patients had their initial endoscopic biopsies (EGDs) reviewed at Memorial Sloan-Kettering Cancer Center (MSKCC). All patients had EUS performed at the time of consultation and on completion of therapy if treated at our center. Antral biopsies were stained with a modified Steiner preparation to determine infection by H pylori.

RESULTS

Gastric low-grade lymphoma was confirmed in 16 of 20 patients; 11 of 16 had previously received antibiotic therapy for biopsy-positive H pylori infection. All gastric lymphomas had an abnormal EUS: eight with discrete tumor masses and eight with gastric wall infiltration (submucosa, n = 4; muscularis propria, n = 3; serosa, n = 1). On completion of lymphoma treatment with chemotherapy, radiotherapy, or surgery, 11 of 16 patients underwent follow-up EUS. Five patients received care elsewhere and did not return for posttreatment EUS. The gastric wall was normal with no evidence of disease on EUS-guided biopsy in eight of 11 patients. The remaining three patients had abnormal gastric walls. One was biopsy-negative and two had residual lymphoma. Four patients were found to have benign lymphoid aggregates in association with H pylori on initial EGD and EUS biopsies. All four patients were previously untreated with antibiotics. EUS showed prominent mucosa, but no significant findings within the gastric wall.

CONCLUSION

EUS appears useful to stage objectively and evaluate therapeutic outcome in the management of gastric, low-grade MALT lymphomas. It also helps to distinguish benign lymphoid aggregates from lymphoma associated with H pylori infection. EUS findings may have a significant impact on assessment and therapeutic recommendations.
Prognostic factors in adenocarcinoma of the gastric cardia: pathologic stage analysis and multivariate regression analysis.
Authors: Kajiyama Y , Tsurumaru M , Udagawa H , Tsutsumi K , Kinoshita Y , Ueno M , Akiyama H
Published: February 2017

PURPOSE

To clarify the pathologic stages of adenocarcinoma of the gastric cardia in which the prognosis is worse than in adenocarcinoma of the middle or distal part of the stomach, and to determine prognostic factors in these stages by multivariate analysis.

PATIENTS AND METHODS

We analyzed 2,536 cases of surgically resected gastric adenocarcinoma of all pathologic stages. Four hundred seventy-two cases of gastric carcinoma, in which cumulative survival of gastric cardia was poor, were subjected to Cox regression analysis for prognostic factors, and to logistic regression analysis for factors influencing venous or lymphatic invasion.

RESULTS

The prognosis of adenocarcinoma of the gastric cardia was inferior when compared with similarly staged carcinomas of the middle or lower part of the stomach when there was invasion of proper muscle layer or subserosal layer, with no lymph node metastasis or with only adjacent (group 1) lymph nodes metastases (T2N0 or T2N1, according to the Japanese classification). In these stages, the prognostic factors were age, histologic type, venous invasion, and location of the tumor in the upper part of the stomach. Tumor location in the upper stomach was also a predictor for the presence of venous invasion.

CONCLUSION

The prognosis of adenocarcinoma of the gastric cardia is poor in patients with T2 tumors with no or few lymph node metastases. Additional treatment after surgery may be necessary to improve the survival of this population.
Race and clinical outcome in breast cancer in a series with long-term follow-up evaluation.
Authors: Heimann R , Ferguson D , Powers C , Suri D , Weichselbaum R R , Hellman S
Published: February 2017

PURPOSE

To compare the outcome of African American (AA) and Caucasian (C) breast cancer patients who had equivalent disease extent and were similarly treated.

PATIENTS AND METHODS

We compared prognostic characteristics, treatment, and outcome of 1,037 C and 481 AA breast cancer patients treated with mastectomy between 1946 and 1987. The median follow-up duration was 15.6 years.

RESULTS

During the study period, there was a successive increase in the percent of patients who presented with early breast cancer. Between 1980 and 1987, 35.1% AA versus 47.6% C patients had < or = 2-cm tumors and 50.0% AA versus 61.9% C patients were node-negative, while between 1946 and 1959, 27.7% AA and 31.3% C had < or = 2-cm tumors and 41.5% AA versus 40.4% C patients were node-negative. The treatments were similar during the study period. The 20-year disease-free survival (DFS) rate of AA compared with C patients with node-negative < or = 2-cm, 2.1- to 4-cm, and greater than 4-cm tumors and of patients with one to three and > or = four positive nodes was not significantly different. Equal-size tumors had similar proportion of positive axillary nodes in AA compared with C patients. The DFS for AA patients compared with C patients was similar in the periods 1946 to 1959, 1960 to 1969, and 1970 to 1979, but was lower between 1980 and 1987 (P = .02). In multivariable analysis, race was not a significant variable.

CONCLUSION

In this large group of uniformly treated breast cancer patients, race was not an independent factor that influenced outcome. The racial differences seen between 1980 and 1987 are likely because of a larger percent of greater than 2-cm and node-positive tumors in AA patients. Education and access to early diagnosis should reduce or eliminate the racial differences seen.
Autologous hapten-modified melanoma vaccine as postsurgical adjuvant treatment after resection of nodal metastases.
Authors: Berd D , Maguire H C , Schuchter L M , Hamilton R , Hauck W W , Sato T , Mastrangelo M J
Published: February 2017

PURPOSE

To determine whether treatment with an autologous whole-cell vaccine modified with the hapten dinitrophenyl (DNP vaccine) is an effective postsurgical adjuvant treatment for melanoma patients with clinically evident nodal metastases.

PATIENTS AND METHODS

Eligible patients had regional nodal metastases that were large enough (> or = 3 cm diameter) to prepare vaccine. Following standard lymphadenectomy, patients were treated with DNP vaccine on a monthly or weekly schedule.

RESULTS

Of 62 patients with metastasis in a single lymph node bed (stage III), 36 are alive after a median follow-up time of 55 months (range, 29 to 76); the projected 5-year relapse-free and overall survival rates are 45% and 58%, respectively. Of 15 patients with metastases in two nodal sites, five are alive with a median follow-up time of 73 months. An unexpected finding was the significantly better survival of older patients; the projected 5-year survival of patients greater than 50 versus < or = 50 years was 71% and 47%, respectively (P = .011, log-rank test). The development of a positive delayed-type hypersensitivity (DTH) response to unmodified autologous melanoma cells was associated with significantly longer 5-year survival (71% v 49%; P = .031). Finally, the median survival time from date of first recurrence was significantly longer for patients whose subcutaneous recurrence exhibited an inflammatory response (> 19.4 v 5.9 months; P < .001).

CONCLUSION

Postsurgical adjuvant therapy with autologous DNP-modified vaccine appears to produce survival rates that are markedly higher than have been reported with surgery alone. Moreover, this approach has some intriguing immunobiologic features that might provide insights into the human tumor-host relationship.
Phase II randomized trial of gallium nitrate plus fluorouracil versus methotrexate, vinblastine, doxorubicin, and cisplatin in patients with advanced transitional-cell carcinoma.
Authors: McCaffrey J A , Hilton S , Mazumdar M , Sadan S , Heineman M , Hirsch J , Kelly W K , Scher H I , Bajorin D F
Published: February 2017

PURPOSE

A phase II randomized trial of gallium nitrate/fluorouracil (5-FU) versus dose-intense methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was performed in poor-risk patients with advanced urothelial tract tumors. The efficacy and toxicity of these regimens were compared. Assessment of dose-intense M-VAC as salvage treatment in patients who failed to respond to the gallium nitrate/5-FU regimen was also performed.

PATIENTS AND METHODS

Thirty-four patients who had not received prior systemic chemotherapy were randomized to either arm of the study. All patients had one or more clinical features predicting a low likelihood of durable complete response to standard chemotherapy, ie, weight loss, visceral metastases, and low performance status. Gallium nitrate and 5-FU were each administered by continuous 5-day infusions every 28 days. M-VAC was recycled every 21 days, with prophylactic recombinant human granulocyte colony-stimulating factor (rh-G-CSF).

RESULTS

Two of 17 patients (12%; 95% confidence interval [CI], 1.4% to 36.4%) had a major response to gallium nitrate/5-FU. Sixteen of 17 patients treated with M-VAC (94%; 95% CI, 71.3% to 99.8%) demonstrated a major response. Five of 12 patients who failed to respond to the gallium nitrate/5-FU combination responded to M-VAC as second-line therapy (42%; 95% CI, 15.2% to 72.3%). Median survival for the gallium nitrate and 5-FU arm was 19 versus 17 months for the M-VAC arm, with a median follow-up duration of 35 months (range, 2 to 51) for all patients. Dose-intense M-VAC was associated with a greater incidence of neutropenia and thrombocytopenia.

CONCLUSION

Dose-intense M-VAC is superior to gallium nitrate/5-FU in poor-risk patients (P < .0001). Despite the overall high response rate, the median survival for patients with M-VAC remained unsatisfactory. Similar survival distributions were observed for patients who received investigational therapy followed by cisplatin-based therapy and patients treated with initial cisplatin-based therapy.
Dose-finding study and pharmacokinetics of epirubicin and paclitaxel over 3 hours: a regimen with high activity and low cardiotoxicity in advanced breast cancer.
Authors: Conte P F , Baldini E , Gennari A , Michelotti A , Salvadori B , Tibaldi C , Danesi R , Innocenti F , Gentile A , Dell'Anna R , Biadi O , Mariani M , Del Tacca M
Published: February 2017

PURPOSE

To determine the maximum-tolerated dose (MTD) of paclitaxel over 3 hours with a fixed dose of epirubicin, to investigate the plasma pharmacokinetics of this combination, and to evaluate the toxicity and the activity in previously untreated metastatic breast cancer patients.

PATIENTS AND METHODS

Fifty patients with metastatic breast cancer, measurable disease, and normal left ventricular ejection fraction (LVEF) were eligible. Epirubicin was administered as an intravenous (I.V.) bolus at the fixed dose of 90 mg/m2 before the infusion of paclitaxel over 3 hours. The initial dose of paclitaxel was 135 mg/m2 and was increased by 20 mg/m2 in subsequent cohorts of six patients until dose-limiting toxicity (DLT). Plasma pharmacokinetics of paclitaxel and epirubicin was performed at cycle 1 in at least two patients per dose level of paclitaxel (175 up to 225 mg/m2).

RESULTS

The DLT of this combination was febrile neutropenia in two of eight patients who received paclitaxel at 225 mg/m2. The mean peak plasma concentration of paclitaxel ranged between 5.1 and 6.2 micromol/L at doses of 175 to 225 mg/m2. The concentration of epirubicinol decreased from 47.3 +/- 9.4 to 37.9 +/- 7.5 ng/mL in patients treated with paclitaxel 175 and 225 mg/m2. The most relevant toxicity was grade 4 neutropenia (61% of all courses). The pharmacokinetic data of paclitaxel, in particular the time above the threshold level of 0.05 micromol/L, were not significantly related to myelosuppression. Cardiac toxicity was mild: three patients (6%) developed mild congestive heart failure that was responsive to therapy. Among 49 assessable patients, 41 responses (84%; 95% confidence interval [CI], 70% to 92%) were observed, and nine (18%) of these were complete.

CONCLUSION

Our study demonstrates that (1) the MTD is epirubicin 90 mg/m2 and paclitaxel 200 mg/m2; (2) no clear relationship exists between pharmacokinetic data of paclitaxel and myelosuppression, while the increase in the dose of paclitaxel is associated with a reduction in epirubicinol plasma levels; and (3) the association is feasible, with low cardiotoxicity, and has a high activity in metastatic breast cancer.
High-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors.
Authors: Motzer R J , Mazumdar M , Bajorin D F , Bosl G J , Lyn P , Vlamis V
Published: February 2017

PURPOSE

A treatment program that included high-dose carboplatin, etoposide, and cyclophosphamide (CEC) followed by autologous bone marrow transplantation (AuBMT) was investigated as first-line therapy in patients with poor-risk germ cell tumors (GCTs).

PATIENTS AND METHODS

Previously untreated GCT patients with poor-risk features were treated with etoposide, ifosfamide, and cisplatin (VIP) with or without high-dose CEC plus AuBMT. Patients qualified for a change to high-dose CEC if a prolonged clearance of elevated serum tumor markers was observed after two cycles of the cisplatin-containing regimen.

RESULTS

Sixteen patients were treated with VIP alone and 14 with VIP and high-dose CEC. Seventeen patients (57%) achieved a complete response. Twenty are alive (67%) and 15 (50%) are free of disease at a median follow-up time of 30 months. For 23 cycles of high-dose CEC, the median time from AuBMT to a granulocyte count > or = 0.5/microL was 11 days (range, 0 to 14) and to a platelet count 50,000/microL, 19 days (range, 14 to 34). The survival of 58 patients treated in two of our center's programs that incorporated high-dose chemotherapy (high-dose carboplatin plus etoposide [CE] and CEC) was compared with our prior experience with conventional-dose cisplatin chemotherapy alone in poor-risk GCT. Patients treated with marker-dependent, early-intervention high-dose chemotherapy experienced longer survival (P = .001).

CONCLUSION

In this setting, high-dose CEC was well tolerated, cumulative toxicity was lacking, and the recovery of blood counts after AuBMT was rapid. A randomized trial has been initiated to investigate further the role of high-dose CEC in first-line therapy for patients with poor-risk GCT.
Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin.
Authors: Xiao H , Mazumdar M , Bajorin D F , Sarosdy M , Vlamis V , Spicer J , Ferrara J , Bosl G J , Motzer R J
Published: February 2017

PURPOSE

To assess the durability of response and overall survival for patients with good-risk metastatic germ cell tumors (GCT) treated with four cycles of etoposide and cisplatin (EP).

PATIENTS AND METHODS

Two hundred fourteen patients treated with EP on two consecutive randomized trials for good-risk metastatic GCT were the subject of this retrospective study. The response to therapy, relapse and survival status, and results of salvage therapy are reported.

RESULTS

One hundred ninety-five patients (91%) achieved a complete response (CR). This included 182 patients (85%) who achieved a CR to chemotherapy alone and 13 patients (6%) who achieved a CR to chemotherapy plus surgical resection of viable GCT. Seventeen patients (9%) have relapsed from CR. The median time to relapse was 10 months, and the longest duration from treatment to relapse was 36 months in a patient who received three of four planned courses of therapy. Eight patients who either achieved an incomplete response (IR) or relapsed were rendered continuously disease-free by salvage therapy and are alive. One hundred eighty-three patients (86%) are alive at a median follow-up of 7.6 years.

CONCLUSION

Four cycles of EP constitute effective therapy and can be offered to patients with good-risk GCT. In patients with intermediate- and poor-risk GCT, clinical trials remain a priority to identify more effective treatment.
Use of chest computed tomography in the staging of pediatric Wilms' tumor: interobserver variability and prognostic significance.
Authors: Wilimas J A , Kaste S C , Kauffman W M , Winer-Muram H , Morris R , Luo X , Boyett J M
Published: February 2017

PURPOSE

To determine the specificity and prognostic significance of computed tomography (CT) of the chest in pediatric Wilms' tumor.

PATIENTS AND METHODS

Patients treated for newly diagnosed Wilms' tumor at St Jude Children's Research Hospital between December 1978 and July 1995 were included in the study if an initial chest radiograph and CT were available and if pulmonary involvement (determined by chest radiographs) was absent. For the 202 patients studied, radiographs and CT scans were reviewed blindly and independently by three experienced radiologists for the presence of pulmonary nodules. Outcome variables consisted of intraobserver variability (in a subsample of 40 cases) and concordance between ratings on radiographs and CT scans (both by McNemar's test), interrater variability (by logistic regression), and the cumulative incidence of pulmonary relapse for patients with and without positive CT scans, by reviewer.

RESULTS

As expected, ratings of pulmonary involvement on radiographs were discordant with CT ratings. There was marked variability among reviewers in CT ratings (P = .0001). Of 202 CT scans, 78 were read as positive by at least one reviewer, 41 were rated positive by only one reviewer, 18 by two reviewers, and 19 by all three. Intrarater variability on repeat reviews was not significant. Patients with nodules identified on CT had a significantly higher pulmonary relapse rate when analyzed separately by reviewer. However, for the 14 patients who had pulmonary relapse, CT scans were rated positive by all three reviewers in only five cases and as negative by all three in another five cases.

CONCLUSION

The variability in interpretation of chest CT scans in patients with Wilms' tumor limits the predictive utility of these studies. Optimal, standardized techniques and central review are essential if chest CT is to be used for staging in cooperative studies.
EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients.
Authors: Bower M , Newlands E S , Holden L , Short D , Brock C , Rustin G J , Begent R H , Bagshawe K D
Published: February 2017

PURPOSE

To evaluate the results of etoposide, methotrexate, and dactinomycin alternating with cyclophosphamide and vincristine (EMA/CO) chemotherapy in women with high-risk gestational trophoblastic tumors (GTT) and to document the middle- and long-term toxicity of the regimen.

PATIENTS AND METHODS

A total of 272 consecutive women with high-risk GTT, including 121 previously treated patients, were treated with weekly EMA/CO. The median follow-up duration is 4.5 years (range, 1 to 16).

RESULTS

The cumulative 5-year survival rate is 86.2% (95% confidence interval, 81.9% to 90.5%). No deaths from GTT have occurred later than 2 years after the end [corrected] of EMA/CO. In a multivariate model, adverse prognostic factors were the presence of liver metastases (P < .0001), interval from antecedent pregnancy (P < .0001), brain metastases (P = .0008), and term delivery of antecedent pregnancy (P = .045). There were 11 (4%) early deaths, while 213 patients (78%) achieved a complete remission. Forty-seven (17%) developed drug resistance to EMA/CO, of whom 33 (70%) were salvaged by further cisplatin-based chemotherapy and surgery. Two women developed acute myeloid leukemia, two cervical malignancy, and one gastric adenocarcinoma after EMA/CO. More than half (56%) of the women who had fertility-conserving surgery and who have been in remission at least 2 years have become pregnant since the completion of EMA/CO, with 112 live births, including three infants with congenital abnormalities.

CONCLUSION

EMA/CO is an effective and well-tolerated regimen for high-risk GTT. More than half of the women will retain their fertility; however, there is a small but significant risk of second malignancy.
Are there sex biases in standardized tests of radiation oncology knowledge?
Authors: Halperin E C , Broadwater G J
Published: February 2017

PURPOSE/OBJECTIVE

Recent studies have identified biases directed against women in standardized tests. We tested for the existence of such biases in the American College of Radiology (ACR) In-Training Examination in Radiation Oncology and the American Board of Radiology (ABR) Written Radiation Oncology Board Examination.

MATERIALS AND METHODS

Our request to the ABR to permit us to study performance on their examinations, as a function of sex, was refused. We obtained scores, through the cooperation of six academic radiation oncology departments, for residents-in-training taking the in-service examination and candidates taking the written board examination for the first time. Test results for 1984 to 1995 were blinded as to name, but not sex or institution of training. For the in-service examination, scores are reported as percentiles normalized to the year of training. The effect of multiple scores for the same resident was assessed using a repeated-measures analysis of variance. Residents were nested within each sex/institution combination and crossed with training year and calendar year. The effects of three factors (sex, institution, and year the examination was taken) on the results of the biology, physics, and clinical sections were evaluated with an analysis of variance. The interactions of sex with institution and year were included to determine the scope of the sex effect. For the board examination, scores are reported as percentiles, as well as an overall pass/ fail outcome. An analyses of variance was performed similar to that used for the in-service examination. In addition, Fisher's exact test and logistic regression were used to analyze overall outcome (pass/fail).

RESULTS

We obtained data for 79 residents (48 men and 31 women, 1.54:1) who took the in-service examinations 165 times. Sixty-two residents (41 men and 21 women, 1.95:1) had an initial sitting for the ABR written examination. On the in-service examination, for the biology, physics, and clinical subsections, calendar year, training year, and sex did not have a significant effect on examinees scores. Institution of training had a significant effect (P < .02) on the scores in biology and physics. The total in-service examination scores were not significantly influenced by calendar year, training year, or sex. Institution of training has a strong influence on overall score (P = .03) and the interaction of sex with training year is near significance level (P = .06). The power for our statistical tests ranged from 0.88 to 0.99. On the board examination, sex, institution of training, year the examination was taken, and interaction of sex with year or sex with institution of training did not have a significant effect on test scores. Pass rates were 90% for men versus 81% for women (P = .43).

CONCLUSION

Sex did not significantly influence the results of the in-service examination or the written board examination. Institution of training is the strongest influence on the results of the in-service examination.
Treatment of Advanced Hodgkin's Disease With Chemotherapy—Comparison of MOPP/ABV Hybrid Regimen With Alternating Courses of MOPP and ABVD
Authors: Connors Joseph M. , Klimo Paul , Adams Grenfell , Burns Bruce F. , Cooper Ian , Meyer Ralph M. , O'Reilly Susan E. , Pater Joseph , Quirt Ian , Sadura Anna , Shustik Chaim , Skillings Jamey , Sutcliffe Simon , Verma Shailendra , Yoshida Sam , Zee Benny
Published: February 2017

The institution affiliation section on page 1638 of the April 1997 article entitled, "Treatment of Advanced Hodgkin's Disease With Chemotherapy—Comparison of MOPP/ABV Hybrid Regimen With Alternating Courses of MOPP and ABVD: A Report From the National Cancer Institute of Canada Clinical Trials Group" by Connors, et al (J Clin Oncol 15:1638–1645, 1997) was incomplete. The "London Regional Cancer Centre, London, Ontario, Canada" should have been included in the listing of author-affiliated institutions.
Elevation of homocysteine and excitatory amino acid neurotransmitters in the CSF of children who receive methotrexate for the treatment of cancer.
Authors: Quinn C T , Griener J C , Bottiglieri T , Hyland K , Farrow A , Kamen B A
Published: February 2017

PURPOSE

Folate deficiency, either by diet or drug, increases plasma homocysteine (Hcy). Hcy damages cerebrovascular endothelium, and hyperhomocysteinemia is a risk factor for stroke. Hcy is metabolized to excitatory amino acid (EAA) neurotransmitters, such as homocysteic acid (HCA) and cysteine sulfinic acid (CSA), which may cause seizures and excitotoxic neuronal death. We postulated that excess Hcy and EAA neurotransmitters may partly mediate methotrexate (MTX)-associated neurotoxicity.

PATIENTS AND METHODS

In this retrospective analysis, we used high-performance liquid chromatography (HPLC) to measure Hcy, HCA, and CSA in CSF from two groups of children: (1) a control group of patients with no MTX exposure, and (2) a treatment group of patients who had received MTX no more than 7 days before a scheduled lumbar puncture.

RESULTS

The treatment group had a significantly (P = .0255) greater concentration of Hcy in CSF (0.814 micromol/L +/- 0.215 [mean +/- SEM], n = 23) than the control group (0.210 micromol/L +/- 0.028, n = 34). HCA and CSA were not detected in CSF from control patients (n = 29); however, MTX caused marked accumulation of CSF HCA (119.1 micromol/L +/- 32.0, n = 16) and CSA (28.4 micromol/L +/- 7.7, n = 16) in the treatment group. Patients with neurologic toxicity at the time of lumbar puncture had many of the highest concentrations of Hcy, HCA, and CSA.

CONCLUSION

These data support our hypothesis that MTX-associated neurotoxicity may be mediated by Hcy and excitotoxic neurotransmitters.
Evaluation of tyrosinase mRNA as a tumor marker in the blood of melanoma patients.
Authors: Jung F A , Buzaid A C , Ross M I , Woods K V , Lee J J , Albitar M , Grimm E A
Published: February 2017

PURPOSE

The value of tyrosinase messenger RNA (mRNA) detection in the peripheral blood by reverse-transcription polymerase chain reaction (RT-PCR) as a melanoma marker remains controversial. The purpose of this study was to compare the sensitivities of two different blood processing techniques for tyrosinase mRNA detection and evaluate its potential clinical value.

METHODS

A total of 50 patients with progressive stage IV melanoma was studied. Two blood processing methods were used: RNA extraction from the whole blood and RNA extraction from density gradient-isolated peripheral-blood mononuclear cells (PBMC). The RNA samples were tested with a sensitive nested-primer RT-PCR assay. RT-PCR results were also correlated with serum lactate dehydrogenase (LDH), treatment status, and presence of visceral versus nonvisceral metastases.

RESULTS

Thirteen (26%) of the density gradient and five (10%) of the whole blood processed samples were PCR positive (P = .011). Serum LDH levels were found to be significantly higher in PCR-positive PBMC-processed patients (P = .015). There was no significant difference in the detection rates between visceral versus nonvisceral metastases or between prior treatment versus no prior treatment.

CONCLUSION

Using a density gradient method to process the blood samples resulted in a higher detection rate of tyrosinase mRNA than extracting the RNA from the whole blood. However, the relatively low sensitivity in patients with disseminated and progressive disease compared with other reports suggests that tyrosinase mRNA may be of limited value in the management of malignant melanoma.
Randomized trial of alternating versus sequential radiotherapy/chemotherapy in limited-disease patients with small-cell lung cancer: a European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group Study.
Authors: Gregor A , Drings P , Burghouts J , Postmus P E , Morgan D , Sahmoud T , Kirkpatrick A , Dalesio O , Giaccone G
Published: February 2017

PURPOSE

To evaluate the effectiveness of alternating or sequential schedules of cyclophosphamide, doxorubicin, and etoposide (CDE) chemotherapy and irradiation in patients with previously untreated small-cell lung cancer (SCLC).

MATERIALS AND METHODS

A total of 335 eligible patients were randomized between five courses of CDE chemotherapy followed by thoracic irradiation 50 Gy in 20 daily fractions (S) and the same total dose of chemotherapy and irradiation split into four courses of five daily fractions delivered on days 14 to 21 of the second and subsequent chemotherapy courses (A). Patients had a median age of 61 years (range, 33 to 75); 224 (66%) were male; the Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 or 1 in 311; and 254 had weight loss less than 10%.

RESULTS

The overall median survival duration was 15 months, with 62% (95% confidence interval [CI], 57% to 67%) 1-year, 25% (95% CI, 20% to 30%) 2-year, and 14% (95% CI, 10% to 18%) 3-year survival rates. There was no significant difference between the arms. The median survival time was 14 months in A and 15 months in S. One-year survival was 60% in A (95% CI, 53% to 67%) and 64% in S (95% CI, 57% to 71%); 2-year survival was 26% in A (95% CI, 19% to 33%) and 23% in S (95% CI, 16% to 30%); and 3-year survival was 12% in A (95% CI, 6% to 18%) and 15% in S (95% CI, 9% to 21%). World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 90% of A and 77% of S patients (P < .001) and WHO grade 3 and 4 thrombocytopenia in 33% of A and 20% of S patients (P < .001). Rates of other acute and late toxicities were similar in both arms. Hematologic toxicity compromised treatment dose delivery; less than 50% of A patients received greater than 95% of prescribed chemotherapy and 77% their full radiation course, compared with 60% and 93% for arm S (P < .009). Local relapse was the site of first failure in 60% of all patients and 75% of these suffered an in-field relapse; no difference could be seen between the two arms.

CONCLUSION

This trial failed to confirm the superiority of an alternating schedule of delivery. For this combination of chemotherapy and irradiation, hematologic toxicity compromised treatment delivery and could have contributed to the overall result. The poor rates of local control are disappointing and require intensification of the radiation therapy strategy.
Breast conservation and prolonged chemotherapy for locally advanced breast cancer: the University of Michigan experience.
Authors: Merajver S D , Weber B L , Cody R , Zhang D , Strawderman M , Calzone K A , LeClaire V , Levin A , Irani J , Halvie M , August D , Wicha M , Lichter A , Pierce L J
Published: February 2017

PURPOSE

To determine whether breast conservation and prolonged neoadjuvant chemotherapy have efficacy in locally advanced breast cancer (LABC), as measured by survival and rate of breast conservation.

MATERIALS AND METHODS

Eighty-nine patients with stage III disease were enrolled at the University of Michigan (UM) onto a prospective nonrandomized trial. Patients received nine 21-day cycles of neoadjuvant chemohormonal therapy that consisted of doxorubicin 30 mg/m2 and cyclophosphamide 750 mg/m2 intravenously on day 1, conjugated estrogens 0.625 mg orally twice daily on days 6 to 8, methotrexate 40 mg/m2 and fluorouracil 500 mg/m2 intravenously on day 8, and tamoxifen 10 mg orally twice daily on days 9 to 14. Patients with a negative biopsy received radiation only, while those with residual disease underwent mastectomy and postoperative radiotherapy. Eight more cycles of chemohormonal therapy were administered after local-regional therapy.

RESULTS

The clinical response rate to neoadjuvant therapy was 97%, 28% of patients had a complete pathologic response evaluated at biopsy. Five-year overall and disease-free survival probabilities were 54% and 44%, respectively. The median disease-free survival time was 2.4 years. The 5-year actuarial rates of local-regional control with local failure as only first failure were 82% and 78% following radiotherapy, and mastectomy and radiotherapy, respectively (P = .99).

CONCLUSION

Prolonged neoadjuvant chemohormonal therapy and biopsy-driven local therapy have efficacy in LABC, with 28% of patients being candidates for breast conservation and a 5-year overall survival rate of 54%.