bluuebunny/crossref_metadata_2025 huggingface dataset:
How Are You Feeling? Who Wants To Know? Patients’ and Oncologists’ Preferences for Discussing Health-Related Quality-of-Life Issues
Authors: Detmar S.B. , Aaronson N.K. , Wever L.D. V. , Muller M. , Schornagel J.H.
Published: February 2017

PURPOSE: This study investigated (1) the attitudes of cancer patients toward discussing health-related quality-of-life (HRQL) issues; (2) the association between such attitudes and patients’ characteristics; and (3) oncologists’ attitudes and self-reported behavior regarding these same issues.

PATIENTS AND METHODS: Two hundred seventy-three patients receiving palliative chemotherapy and ten physicians were asked to complete a series of questionnaires.

RESULTS: Almost all patients wanted to discuss their physical symptoms and physical functioning and were also willing to address their emotional functioning and daily activities. However, 25% of the patients were only willing to discuss these latter two issues at the initiative of their physician. Patients varied most in their willingness to discuss their family and social life, with 20% reporting no interest in discussing these issues at all. Female patients were more reluctant to discuss various HRQL issues than male patients. Older and less well-educated patients were more likely to prefer that their physician initiate discussion of HRQL issues. All physicians considered it to be primarily their task to discuss the physical aspects of their patients’ health, whereas four physicians indicated that discussion of psychosocial issues was a task to be shared with other health care providers. All physicians indicated that they generally defer to their patients in initiating discussion of psychosocial issues.

CONCLUSION: Although both patients and oncologists seem willing to discuss a wide range of HRQL issues, communication regarding psychosocial issues may be hampered by competing expectations as to who should take the lead in initiating such discussions.
Treatment of Brain Metastases of Small-Cell Lung Cancer: Comparing Teniposide and Teniposide With Whole-Brain Radiotherapy—A Phase III Study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group
Authors: Postmus Pieter E. , Haaxma-Reiche Hanny , Smit Egbert F. , Groen Harry J. M. , Karnicka Hanna , Lewinski Tadeusz , van Meerbeeck Jan , Clerico Mario , Gregor Anna , Curran Desmond , Sahmoud Tarek , Kirkpatrick Anne , Giaccone Giuseppe
Published: February 2017

PURPOSE: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation.

PATIENTS AND METHODS: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m2 was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain.

RESULTS: One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P < .001). Time to progression in the brain was longer in the combined-modality group (P = .005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P = .087).

CONCLUSION: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.
Randomized, Multicenter Trial of Fluorouracil Plus Leucovorin Administered Either Via Hepatic Arterial or Intravenous Infusion Versus Fluorodeoxyuridine Administered Via Hepatic Arterial Infusion in Patients With Nonresectable Liver Metastases From Colorectal Carcinoma
Authors: Lorenz Matthias , Müller Hans-Helge ,   for the German Cooperative Group on Liver Metastases
Published: February 2017

PURPOSE: To assess the efficacy and tolerability of three treatments for patients with documented adenocarcinoma of the colon and/or rectum who have undergone complete resection of primary tumor and have nonresectable liver metastases that do not exceed 75% of the liver volume.

PATIENTS AND METHODS: A total of 168 patients at 25 treatment centers were enrolled onto this prospective, multicenter, randomized study. The three treatment arms were as follows: (1) fluorouracil (5-FU)/leucovorin (LV) administered via hepatic arterial infusion (HAI), (2) 5-FU/LV administered via intravenous (IV) infusion, and (3) fluorodeoxyuridine (FUDR) administered via HAI.

RESULTS: Median times to disease progression for the three treatment arms were as follows: 9.2 months for patients treated with HAI 5-FU/LV, 6.6 months for IV 5-FU/LV, and 5.9 months for HAI FUDR. Median survival times for patients treated with HAI 5-FU/LV, IV 5-FU/LV, and HAI FUDR were 18.7 months, 17.6 months, and 12.7 months, respectively. There was a nearly two-fold increase in time to progression in addition to a survival benefit among patients with an intrahepatic tumor burden of less than 25% who were treated with HAI 5-FU/LV. The most common adverse events were stomatitis, nausea and vomiting, skin irritation, diarrhea, and elevated serum levels of liver enzymes. Some patients exhibited severe reactions, including biliary sclerosis and chemical hepatitis.

CONCLUSION: Although the use of HAI 5-FU/LV as a means of treating liver metastases after resection of colorectal carcinoma warrants further investigation, it cannot be recommended as a routine therapeutic measure at this time.
Comparison of Chemotherapy With Chemohormonal Therapy as First-Line Therapy for Metastatic, Hormone-Sensitive Breast Cancer: An Eastern Cooperative Oncology Group Study
Authors: Sledge G.W. , Hu P. , Falkson G. , Tormey D. , Abeloff M. ,   for the Eastern Cooperative Oncology Group
Published: February 2017

PURPOSE: Although hormonal therapy represents standard therapy for metastatic hormone-sensitive disease, many patients receive initial chemotherapy because of the location, bulk, or aggressiveness of their disease. It is uncertain whether simultaneous hormonal therapy provides additional benefit compared with chemotherapy alone. Eastern Cooperative Oncology Group trial E3186 was initiated to explore this question.

PATIENTS AND METHODS: Between January 1988 and December 1992, 231 patients with estrogen receptor (ER)–positive or ER-unknown metastatic breast cancer were randomized to receive either chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil [CAF]) or chemohormonal therapy (CAF plus tamoxifen and Halotestin [fluoxymesterone; Pharmacia-Upjohn, Kalamazoo, MI] [CAFTH]) as front-line therapy for metastatic breast cancer. Patients who experienced a complete response to induction therapy either received or did not receive maintenance cyclophosphamide, methotrexate, fluorouracil, prednisone, and TH as a secondary randomization.

RESULTS: The response rates (complete response and partial response) of patients who received CAF and CAFTH were similar (69.2% v 68.9%, respectively; P = .99). Time to treatment failure (TTF) was slightly longer for patients who received chemohormonal therapy compared with chemotherapy alone patients (13.4 months v 10.3 months, respectively; P = .087), and TTF was significantly longer in ER-positive compared with ER-negative patients (17.4 months v 10.3 months, respectively; P = .048). However, ER status had no effect on overall survival (30.0 months for CAF v 29.3 months for CAFTH).

CONCLUSION: In patients with potentially hormone-sensitive metastatic breast cancer, chemohormonal therapy prolongs TTF for ER-positive patients without improving overall survival.
European Phase II Study of Rituximab (Chimeric Anti-CD20 Monoclonal Antibody) for Patients With Newly Diagnosed Mantle-Cell Lymphoma and Previously Treated Mantle-Cell Lymphoma, Immunocytoma, and Small B-Cell Lymphocytic Lymphoma
Authors: Foran James M. , Rohatiner Ama Z. S. , Cunningham David , Popescu Razvan A. , Solal-Celigny Philippe , Ghielmini Michele , Coiffier Bertrand , Johnson Peter W. M. , Gisselbrecht Christian , Reyes Felix , Radford John A. , Bessell Eric M. , Souleau Bertrand , Benzohra Aziz , Lister T. Andrew
Published: February 2017

PURPOSE: Mantle-cell lymphoma (MCL), immunocytoma (IMC), and small B-cell lymphocytic lymphoma (SLL) are B-cell malignancies that express CD20 and are incurable with standard therapy. A multicenter phase II study was conducted to assess the toxicity and the overall response rates (RR) and complete response (CR) rates to rituximab (chimeric anti-CD20 monoclonal antibody).

PATIENTS AND METHODS: Between January 1997 and January 1998, 131 patients with newly diagnosed MCL (MCL1; n = 34) and previously treated MCL (MCL2; n = 40), IMC (n = 28), and SLL (n = 29) received rituximab 375 mg/m2/wk for 4 weeks via intravenous infusion. Restaging studies were performed 1 and 2 months after treatment. An analysis of the duration of response was conducted in December 1998.

RESULTS: Eleven patients were unassessable, including one who died of splenic rupture after the first infusion. The RR among the 120 assessable patients was 30% (36 of 120 patients). The RR by histology was as follows: MCL1, 38%; MCL2, 37%; IMC, 28%; and SLL, 14%. Ten patients, all with MCL, achieved CR. The median duration of response in MCL was 1.2 years. Immediate side effects were common and usually responded to adjustments in the infusion rate. There were 31 episodes of infection after treatment; most cases were mild. Cardiac arrhythmia and ophthalmologic side effects occurred in 10 and nine patients, respectively, including one case of severe loss of visual acuity.

CONCLUSION: Single-agent rituximab has moderate activity in MCL and IMC but only limited activity in SLL. The duration of response in MCL was similar to that previously reported in follicular lymphoma. Its use in combination with cytotoxic chemotherapy to increase the CR rate is warranted in MCL and IMC.
Targeting Superficial Bladder Cancer by the Intravesical Administration of Copper-67–Labeled Anti-MUC1 Mucin Monoclonal Antibody C595
Authors: Hughes O.D. M. , Bishop M.C. , Perkins A.C. , Wastie M.L. , Denton G. , Price M.R. , Frier M. , Denley H. , Rutherford R. , Schubiger P.A.
Published: February 2017

PURPOSE: More effective intravesical agents are required to limit the recurrence and progression of superficial bladder cancer. This study assessed the ability of copper-67 (67Cu)-C595 murine antimucin monoclonal antibody to bind selectively to superficial bladder tumors when administered intravesically, with a view to its development for therapy.

PATIENTS AND METHODS: Approximately 20 MBq of 67Cu-C595 monoclonal antibody was administered intravesically to 16 patients with a clinical indication of superficial bladder cancer. After 1 hour, the bladder was drained and irrigated. Tissue uptake was assessed by imaging and by the assay of tumor and normal tissues obtained by endoscopic resection.

RESULTS: Tumor was correctly identified in the images of 12 of 15 patients who were subsequently found to have tumors. Assay of biopsy samples at 2 hours showed a mean tumor uptake of 59.4% of the injected dose per kilogram (SD = 48.0), with a tumor-to-normal tissue ratio of 14.6:1 (SD = 20). After 24 hours (n = 5), this decreased to 4.3% of the injected dose per kilogram (SD = 2.9), with a tumor-to-normal tissue ratio of 1.8:1 (SD = 0.8).

CONCLUSION: This study indicates a promising method for the treatment of superficial bladder cancer. Although the mean initial tumor uptake was high, effective therapy of bladder tumors will require an increased retention of the cytotoxic radionuclide in tumor tissue.
Effects of Adjuvant Tamoxifen on the Endometrium in Postmenopausal Women With Breast Cancer: A Prospective Long-Term Study Using Transvaginal Ultrasound
Authors: Gerber Bernd , Krause Annette , Müller Heiner , Reimer Toralf , Külz Thomas , Makovitzky Josef , Kundt Guenter , Friese Klaus
Published: February 2017

PURPOSE: To study the value of transvaginal ultrasound (TVS) in endometrial screening of postmenopausal breast cancer patients treated with tamoxifen.

PATIENTS AND METHODS: In 247 tamoxifen-treated (20 to 30 mg/d for ≥ 2 years) women and 98 controls, the endometrium was prospectively followed-up by means of TVS every 6 months for up to 5 years. Patients with homogeneous endometrium of more than 10-mm thickness were then scanned repeatedly every 3 months.

RESULTS: The mean endometrial thickness was 3.5 ± 1.1 mm before treatment and increased to a maximum of 9.2 ± 5.1 mm after 3 years of tamoxifen application (P < .0001), which was significantly (P < .0001) thicker compared with controls. Fifty-two asymptomatic patients with thickened or morphologically suspect endometrium underwent hysteroscopy and dilatation and curettage (D&C), resulting in four uterine perforations. Histopathologically, atrophy was found in 38 patients (73.1%), polyps in nine, hyperplasia in four, and endometrial cancer in one case. In 20 screened patients who reported vaginal bleeding, five atrophies (25%), five polyps, four hyperplasias, and two endometrial cancers were found. Before hysteroscopy and D&C were performed, 36 (69.2%) of 52 asymptomatic and four (20%) of 20 symptomatic patients were scanned by repeated TVS over 2 to 30 months. Invasive diagnostic procedures were significantly (P < .05) more frequent in younger and obese patients. In the controls, one asymptomatic polyp and one symptomatic hyperplasia were found.

CONCLUSION: In tamoxifen-treated patients, TVS offered a high false-positive rate, even with a cutoff value of 10 mm for endometrial thickness and repeated TVS scans. Increased iatrogenic morbidity and only one asymptomatic endometrial carcinoma do not warrant endometrial screening by TVS in tamoxifen-treated patients.
Breast Imaging With Positron Emission Tomography and Fluorine-18 Fluorodeoxyglucose: Use and Limitations
Authors: Avril N. , Rosé C.A. , Schelling M. , Dose J. , Kuhn W. , Bense S. , Weber W. , Ziegler S. , Graeff H. , Schwaiger M.
Published: February 2017

PURPOSE: To evaluate the diagnostic value of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) for the diagnosis of primary breast cancer.

PATIENTS AND METHODS: Preoperatively, 144 patients with masses suggestive of breast cancer underwent PET imaging of the breast. To identify breast cancer by increased metabolic activity, parametric FDG-PET images were analyzed for increased tracer uptake applying conventional image reading (CIR) and sensitive image reading (SIR). One hundred eighty-five breast tumors were evaluated by histology, revealing 132 breast carcinomas and 53 benign masses.

RESULTS: Breast carcinomas were identified with an overall sensitivity of 64.4% (CIR) and 80.3% (SIR). The increase in sensitivity (SIR) resulted in a noticeable decrease in specificity, from 94.3% (CIR) to 75.5% (SIR). At stage pT1, only 30 (68.2%) of 44 breast carcinomas were detected, compared with 57 (91.9%) of 62 at stage pT2. A higher percentage of invasive lobular carcinomas were false-negative (65.2%) compared with invasive ductal carcinomas (23.7%). Nevertheless, positive PET scans provided a high positive-predictive value (96.6%) for breast cancer.

CONCLUSION: Partial volume effects and varying metabolic activity (dependent on tumor type) seem to represent the most significant limitations for the routine diagnostic application of PET. The number of invasive procedures is therefore unlikely to be significantly reduced by PET imaging in patients presenting with abnormal mammography. However, the high positive-predictive value, resulting from the increased metabolic activity of malignant tissue, may be used with carefully selected subsets of patients as well as to determine the extent of disease or to assess therapy response.
Prospective Validation of Renal Function–Based Carboplatin Dosing in Children With Cancer: A United Kingdom Children’s Cancer Study Group Trial
Authors: Thomas Huw , Boddy Alan V. , English Martin W. , Hobson Rachel , Imeson John , Lewis Ian , Morland Bruce , Pearson Andrew D. J. , Pinkerton Ross , Price Lisa , Stevens Michael , Newell David R.
Published: February 2017

PURPOSE: Carboplatin dosing in adults with cancer is based on renal function. The purpose of the current study was to validate a previously developed pediatric carboplatin-dosing formula.

PATIENTS AND METHODS: Thirty-eight pediatric patients were randomized to receive a carboplatin dose calculated according to surface area or a renal function–based dosing formula. On the next course of therapy, the alternative dosing method was used for each patient. Carboplatin pharmacokinetics (based on free plasma platinum concentrations) were measured after both courses.

RESULTS: The mean observed areas under the carboplatin concentration–versus-time curve (AUCs) after renal function– and surface area–based dosing were 98% and 95% of the target AUCs, respectively. The variation in the observed AUC was significantly less after renal function–based dosing (F test, P = .02), such that 74% of courses had an observed AUC within ± 20% of the target value, versus 49% for courses after dosing according to surface area. Only one of 22 courses at the center with the most experience with renal function–based dosing was associated with an AUC outside ± 20% of the target value, versus nine of 22 courses after surface area–based dosing in the same center. There was a relationship (r2 = .71) between carboplatin AUC and thrombocytopenia in 10 neuroblastoma patients treated with a combination of carboplatin, vincristine, etoposide, and cyclophosphamide.

CONCLUSION: Renal function–based carboplatin dosing in children results in more consistent drug exposure than surface area–based drug administration.
Role of a Doxorubicin-Containing Regimen in Relapsed and Resistant Lymphomas: An 8-Year Follow-Up Study of EPOCH
Authors: Gutierrez Martin , Chabner Bruce A. , Pearson Debra , Steinberg Seth M. , Jaffe Elaine S. , Cheson Bruce D. , Fojo Antonio , Wilson Wyndham H.
Published: February 2017

PURPOSE: Curative up-front regimens for non-Hodgkin’s lymphomas contain doxorubicin, vincristine, and cyclophosphamide, whereas salvage regimens generally contain non–cross-resistant agents. We hypothesized that up-front agents may be highly effective for salvage and developed an infusional regimen based on in vitro evidence of increased efficacy.

PATIENTS AND METHODS: A prospective phase II study of etoposide, vincristine, and doxorubicin over 96 hours with bolus cyclophosphamide and oral prednisone (EPOCH) was performed in 131 patients with relapsed or resistant lymphoma.

RESULTS: Seventy-nine percent of patients had aggressive histologies, 46% were considered high risk by the International Prognostic Index, and 34% had resistant disease. Eighty-eight percent of patients had received at least four of the agents in EPOCH, and 94% had received doxorubicin. In 125 assessable patients, 29 (24%) achieved complete responses and 60 (50%) achieved partial responses. Among 42 patients with resistant disease, 57% responded, and in 28 patients with relapsed aggressive de novo lymphomas, 89% responded with 54% complete responses. With a median follow-up of 76 months, the overall and event-free survivals (EFS) were 17.5 and 7 months, respectively. In 33 patients with sensitive aggressive disease who did not receive stem-cell transplantation, EFS was 19% at 36 months. Toxicity was primarily hematologic, with an 18% incidence of febrile neutropenia. No clinically significant cardiac toxicity was observed, despite no maximum cumulative doxorubicin dose.

CONCLUSION: EPOCH is highly effective in patients who had previously received most/all of the same drugs and produces durable remissions in curable subtypes. Salvage regimens need not contain non–cross-resistant agents, and infusional schedules may partially reverse drug resistance and reduce toxicity.
Anastrozole Versus Tamoxifen as First-Line Therapy for Advanced Breast Cancer in 668 Postmenopausal Women: Results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability Study
Authors: Bonneterre J. , Thürlimann B. , Robertson J.F. R. , Krzakowski M. , Mauriac L. , Koralewski P. , Vergote I. , Webster A. , Steinberg M. , von Euler M.
Published: February 2017

PURPOSE: To compare the efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) with that of tamoxifen as first-line therapy for advanced breast cancer (ABC) in postmenopausal women.

PATIENTS AND METHODS: This randomized, double-blind, multicenter study evaluated the efficacy of anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with tumors that were hormone receptor–positive or of unknown receptor status who were eligible for endocrine therapy. The primary end points were time to progression (TTP), objective response (OR), and tolerability.

RESULTS: A total of 668 patients (340 in the anastrozole arm and 328 in the tamoxifen arm) were randomized to treatment and followed-up for a median of 19 months. Median TTP was similar for both treatments (8.2 months in patients who received anastrozole and 8.3 months in patients who received tamoxifen). The tamoxifen:anastrozole hazards ratio was 0.99 (lower one-sided 95% confidence limit, 0.86), demonstrating that anastrozole was at least equivalent to tamoxifen. Anastrozole was also as effective as tamoxifen in terms of OR (32.9% of anastrozole and 32.6% of tamoxifen patients achieved a complete response [CR] or partial response [PR]). Clinical benefit (CR + PR + stabilization of ≥ 24 weeks) rates were 56.2% and 55.5% for patients receiving anastrozole and tamoxifen, respectively. Both treatments were well tolerated. However, incidences of thromboembolic events and vaginal bleeding were reported in fewer patients treated with anastrozole than with tamoxifen (4.8% v 7.3% [thromboembolic events] and 1.2% v 2.4% [vaginal bleeding], respectively).

CONCLUSION: Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Together with the lower observed incidence of thromboembolic events and vaginal bleeding, these findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with ABC.
Quality-of-Life Scores Predict Outcome in Metastatic but Not Early Breast Cancer
Authors: Coates Alan S. , Hürny Christoph , Peterson Harriet F. , Bernhard Jürg , Castiglione-Gertsch Monica , Gelber Richard D. , Goldhirsch Aron ,   for the International Breast Cancer Study Group
Published: February 2017

PURPOSE: We compared the prognostic value of quality-of-life (QL) scores in the adjuvant setting and after relapse in two randomized trials of the International Breast Cancer Study Group.

PATIENTS AND METHODS: More than 2,000 premenopausal and postmenopausal patients with node-positive breast cancer who were participating in randomized trials that compared adjuvant therapies completed QL assessments for physical well-being, mood, appetite, and coping at study entry and at months 3 and 18 if they remained relapse-free and, in case of relapse, at 1 month and at 6 months after relapse. Cox regression models were used to test the relationship between QL scores and disease-free survival (DFS), in the adjuvant setting, or overall survival, in the case of postrelapse QL measurement. All models were stratified by language/country group and included other factors related to QL and/or outcome.

RESULTS: DFS was not significantly predicted by QL scores at baseline or month 18, or by changes in QL score between baseline and months 3 or 18. In contrast, after relapse, QL scores were predictive for subsequent overall survival. One month after relapse, better mood (P = .04) in premenopausal patients and better appetite (P = .005) in postmenopausal patients were associated with longer survival. Six months after relapse, better physical well-being (P = .03) and appetite (P = .03) in premenopausal patients and better physical well-being (P < .0001), mood (P = .002), appetite (P = .0001), and coping (P = .0001) in postmenopausal patients predicted longer survival.

CONCLUSION: Any prognostic significance of QL scores in the adjuvant setting is minimal or obscured by chemotherapy effects, but there is strong prognostic significance of QL scores after disease relapse. The contrast suggests that patient perception of the severity of underlying illness may determine reported QL scores.
Expression of Apoptosis-Related Proteins Is an Independent Determinant of Patient Prognosis in Advanced Ovarian Cancer
Authors: Baekelandt M. , Holm R. , Nesland J.M. , Tropé C.G. , Kristensen G.B.
Published: February 2017

PURPOSE: The present study was undertaken to investigate the prognostic and predictive relevance of the expression of apoptosis-related proteins Bax, Bcl-XL, and Mcl-1 in advanced ovarian cancer.

PATIENTS AND METHODS: Tumor biopsies from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for the expression of Bax, Bcl-XL and Mcl-1 proteins. Their prognostic relevance was examined in a uni- and multivariate survival analysis.

RESULTS: Sixty-six percent of cancer cases expressed Bax, 62% Bcl-XL, and 53% Mcl-1. The expression of Bax correlated with tumor differentiation (P = .016) and less residual disease after surgery (P < .0001). In univariate analysis, Bax expression was associated with improved (P = .0004) prognosis and Mcl-1 expression with poorer (P = .011) prognosis. None of the factors studied was of independent prognostic significance by itself, but when Bax and Bcl-2 expression data were considered together, this combined variable was of independent prognostic significance (P = .0115), together with residual disease status (P = .0016), differentiation grade (P = .0014), and the presence of ascites (P = .0122). Patients with a long median survival (104 months) could be discriminated from those with a short one (16 months) by combining the individual patients’ expression data for p53, Bax, and Bcl-2 with their residual disease status (P < .00001). None of the factors studied was able to predict response to chemotherapy.

CONCLUSION: The expression of selected apoptosis-related proteins is of independent prognostic significance and may be helpful in a molecular substaging of patients with stage III ovarian cancer.
Synovial Sarcoma: A Clinicopathologic, Staging, and Prognostic Assessment
Authors: Spillane Andrew J. , A’Hern Roger , Judson Ian R. , Fisher Cyril , Thomas J. Meirion
Published: February 2017

PURPOSE: Synovial sarcoma (SS) is a common soft tissue sarcoma (STS) with a propensity for young adults and notable sensitivity to chemotherapy (CT). This study provides a current clinicopathologic, staging, and prognostic assessment for SS. The problems with the current American Joint Committee for Cancer (AJCC) Staging System in relation to SS are discussed.

METHODS: Review of a prospective database supplemented by retrospective data.

RESULTS: One hundred fifty patients were assessed; median age was 30 years and median follow-up was 52 months. Overall actuarial 5-year survival rate was 57%. Size trend, but not a cutoff of less than 5 cm versus ≥ 5 cm, was a prognostic indicator (P < .001). The current AJCC/International Union Against Cancer Staging System differentiated prognosis less well than the recently proposed Royal Marsden Hospital Staging System. Age greater than 20 years at diagnosis implied worse prognosis. A local recurrence event was associated with a worse survival (P < .001). Therapeutic CT was administered to 55 patients. Eleven of 19 patients had an objective response to a combination of ifosfamide and doxorubicin. Four cases had complete response after CT. Twenty-one patients had pulmonary metastasectomy, with an actuarial 5-year survival rate of 23%.

CONCLUSION: SS tends to affect young people. In this subtype of STS, size trend is the most significant influence on stage and hence survival; however, smaller SSs have an unexpectedly poor prognosis. Adequate local control may affect survival. SS is often chemosensitive, and given its poor prognosis, multicenter trials of adjuvant therapy are warranted.
Phase I Trial Results of Iodine-131–Labeled Antitenascin Monoclonal Antibody 81C6 Treatment of Patients With Newly Diagnosed Malignant Gliomas
Authors: Cokgor Ilkcan , Akabani Gamal , Kuan Chien-Tsun , Friedman Henry S. , Friedman Allan H. , Coleman R. Edward , McLendon Roger E. , Bigner Sandra H. , Zhao Xiao-Guang , Garcia-Turner Ana M. , Pegram Charles N. , Wikstrand Carol J. , Shafman Timothy D. , Herndon James E. , Provenzale James M. , Zalutsky Michael R. , Bigner Darell D.
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine-131 (131I)–labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinically into surgically created resection cavities (SCRCs) in malignant glioma patients and to identify any objective responses with this treatment.

PATIENTS AND METHODS: In this phase I trial, newly diagnosed patients with malignant gliomas with no prior external-beam therapy or chemotherapy were treated with a single injection of 131I-labeled 81C6 through a Rickham reservoir into the resection cavity. The initial dose was 20 mCi and escalation was in 20-mCi increments. Patients were observed for toxicity and response until death or for a minimum of 1 year after treatment.

RESULTS: We treated 42 patients with 131I-labeled 81C6 mAb in administered doses up to 180 mCi. Dose-limiting toxicity was observed at doses greater than 120 mCi and consisted of delayed neurotoxicity. None of the patients developed major hematologic toxicity. Median survival for patients with glioblastoma multiforme and for all patients was 69 and 79 weeks, respectively.

CONCLUSION: The MTD for administration of 131I-labeled 81C6 into the SCRC of newly diagnosed patients with no prior radiation therapy or chemotherapy was 120 mCi. Dose-limiting toxicity was delayed neurologic toxicity. We are encouraged by the survival and toxicity and by the low 2.5% prevalence of debulking surgery for symptomatic radiation necrosis.
Gene Expression for Dihydropyrimidine Dehydrogenase and Thymidine Phosphorylase Influences Outcome in Epithelial Ovarian Cancer
Authors: Fujiwaki Ritsuto , Hata Kohkichi , Nakayama Kentaro , Fukumoto Manabu , Miyazaki Kohji
Published: February 2017

PURPOSE: Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine salvage enzyme responsible for degradation of thymine, which is produced from thymidine by thymidine phosphorylase (TP). Our purpose was to determine whether DPD affects prognosis in patients with epithelial ovarian cancer and how the two enzymes may interact in such effects.

PATIENTS AND METHODS: DPD gene expression was analyzed by reverse transcription-polymerase chain reaction in 27 samples from normal ovaries and the 85 epithelial ovarian cancers previously studied with regard to TP gene expression.

RESULTS: DPD gene expression was significantly lower in epithelial ovarian cancers than in normal ovaries (P < .0001), whereas TP gene expression and the ratio of TP to DPD gene expression (TP:DPD) were significantly higher in epithelial ovarian cancer (P < .0001 for both). In patients with epithelial ovarian cancer, DPD gene expression and the TP:DPD ratio did not significantly correlate with any clinicopathologic factors. Patients with a high TP:DPD ratio (higher than the median) had significantly poorer outcomes than those with lower ratios (P = .0002). The difference in survival between groups with high and low TP:DPD ratios was greater than the difference between groups with high and low TP gene expression. Multivariate analysis showed the TP:DPD ratio to be the independent prognostic factor (P = .0002). In tumors with high TP gene expression, low DPD gene expression significantly correlated with poor survival (P = .04).

CONCLUSION: Downregulation of DPD gene expression may enhance the negative prognostic effect of high TP gene expression in patients with epithelial ovarian cancer. Certain newly available chemotherapeutic choices may take the TP:DPD ratio into consideration.
Long-Term Risk of Second Malignancy in Survivors of Hodgkin’s Disease Treated During Adolescence or Young Adulthood
Authors: van Leeuwen Flora E. , Klokman Willem J. , Veer Mars B. van’t , Hagenbeek Anton , Krol Augustinus D. G. , Vetter Ursula A. O. , Schaapveld Michael , van Heerde Peter , Burgers J. Marion V. , Somers Reinier , Aleman Berthe M. P.
Published: February 2017

PURPOSE: To quantify the long-term risk of second primary cancers (SCs) in patients diagnosed with Hodgkin’s disease (HD) during adolescence or young adulthood.

PATIENTS AND METHODS: The risk of SCs was assessed in 1,253 patients diagnosed with HD before the age of 40 years and treated in two Dutch cancer centers between 1966 and 1986. The median follow-up duration was 14.1 years.

RESULTS: In all, 137 patients developed SCs, compared with 19.4 cases expected on the basis of incidence rates in the general population (relative risk [RR] = 7.0; 95% confidence interval, 5.9 to 8.3). The 25-year actuarial risk of SC overall was 27.7%. The RR of solid tumors increased greatly with younger age at the first treatment of HD, not only for breast cancer but also for all other solid tumors, with RRs of 4.9, 6.9, and 12.7 for patients first treated at ages 31 to 39 years, 21 to 30 years, and ≤ 20 years, respectively.

Among patients first treated at the age of 20 years or younger, the RR of developing a solid tumor before the age of 40 years was significantly greater than the RR of solid tumor development at ages 40 to 49 years (RR = 27.9 v RR = 4.2; P = .0001). Patients who received salvage chemotherapy had significantly greater risk of solid cancers other than breast cancer than did patients whose treatment was restricted to initial radiotherapy or initial combined-modality treatment (RR = 9.4 and 4.7, respectively; P = .004).

CONCLUSION: After more than 20 years of follow-up, the risk of solid tumors is still much greater in survivors of HD than in the population at large. Reassuringly, the greatly increased risk of solid tumors in patients who were young (≤ 20 years of age) at the first treatment seems to decrease as these patients grow older. Our data suggest that chemotherapy may increase the risk of solid tumors from radiotherapy.
Risk of Second Malignancy After Hodgkin’s Disease in a Collaborative British Cohort: The Relation to Age at Treatment
Authors: Swerdlow A.J. , Barber J.A. , Hudson G. Vaughan , Cunningham D. , Gupta R.K. , Hancock B.W. , Horwich A. , Lister T.A. , Linch D.C.
Published: February 2017

PURPOSE: To assess long-term site-specific risks of second malignancy after Hodgkin’s disease in relation to age at treatment and other factors.

PATIENTS AND METHODS: A cohort of 5,519 British patients with Hodgkin’s disease treated during 1963 through 1993 was assembled and followed-up for second malignancy and mortality. Follow-up was 97% complete.

RESULTS: Three hundred twenty-two second malignancies occurred. Relative risks of gastrointestinal, lung, breast, and bone and soft tissue cancers, and of leukemia, increased significantly with younger age at first treatment. Absolute excess risks and cumulative risks of solid cancers and leukemia, however, were greater at older ages than at younger ages. Gastrointestinal cancer risk was greatest after mixed-modality treatment (relative risk [RR] = 3.3; 95% confidence interval [CI], 2.1 to 4.8); lung cancer risks were significantly increased after chemotherapy (RR = 3.3; 95% CI, 2.4 to 4.7), mixed-modality treatment (RR = 4.3; 95% CI, 2.9 to 6.2), and radiotherapy (RR = 2.9; 95% CI, 1.9 to 4.1); breast cancer risk was increased only after radiotherapy without chemotherapy (RR = 2.5; 95% CI, 1.4 to 4.0); and leukemia risk was significantly increased after chemotherapy (RR = 31.6; 95% CI, 19.7 to 47.6) and mixed-modality treatment (RR = 38.1; 95% CI, 24.6 to 55.9). These risks were generally greater after treatment at younger ages: for patients treated at ages younger than 25 years, there were RRs of 18.7 (95% CI, 5.8 to 43.5) for gastrointestinal cancer after mixed-modality treatment, 14.4 (95% CI, 5.7 to 29.3) for breast cancer after radiotherapy, and 85.2 (95% CI, 45.3 to 145.7) for leukemia after chemotherapy (with or without radiotherapy).

CONCLUSION: Age at treatment has a major effect on risk of second malignancy after Hodgkin’s disease. Although absolute excess risks are greater for older patients, RRs of several important malignancies are much greater for patients who are treated when young. The increased risk of gastrointestinal cancers may relate particularly to mixed-modality treatment, and that of lung cancer to chemotherapy as well as radiotherapy; there are also well-known increased risks of breast cancer from radiotherapy and leukemia from chemotherapy. The roles of specific chemotherapeutic agents in the etiology of solid cancers after Hodgkin’s disease require detailed investigation.
Phase II Multicenter Study of Brief Single-Agent Methotrexate Followed by Irradiation in Primary CNS Lymphoma
Authors: O’Brien P. , Roos D. , Pratt G. , Liew K. , Barton M. , Poulsen M. , Olver I. , Trotter G.
Published: February 2017

PURPOSE: To assess, in a multi-institutional setting, the impact on relapse, survival, and toxicity of adding two cycles of intravenous methotrexate to cranial irradiation for immunocompetent patients with primary CNS lymphoma.

PATIENTS AND METHODS: Forty-six patients with a median age of 58 years and Eastern Cooperative Oncology Group performance status 0 to 3 were entered onto this phase II study. The protocol consisted of methotrexate 1 g/m2 on days 1 and 8 followed by cranial irradiation on day 15. A whole-brain dose of 45 Gy was followed by a boost of 5.4 Gy. Intrathecal chemotherapy and spinal irradiation were given only to patients for whom cytologic examination of CSF was positive for CNS lymphoma. The median follow-up time was 36 months, with a minimum potential follow-up of 12 months.

RESULTS: Median survival was 33 months, with 2-year probability of survival 62% ± 15% (95% confidence interval). Twenty patients have relapsed. The predominant site of relapse was the brain. Neither performance status nor age was found to influence survival. Six patients developed a dementing illness at a median of 16 months after treatment, and three of these died as a consequence.

CONCLUSION: A brief course of intravenous methotrexate before cranial irradiation is associated with 2-year and median survival rates superior to those reported for radiotherapy alone and similar to more intensive combined-modality regimens. Neurotoxicity remains an important competing risk for these patients.
Clinical Progression of Breast Cancer Malignant Behavior: What to Expect and When to Expect it
Authors: Heimann Ruth , Hellman Samuel
Published: February 2017

PURPOSE: Seemingly localized breast cancer is a heterogeneous mix of truly localized cancers and cancers with occult metastases. Our purpose is to determine the parameters of metastatic proclivity for the different clinical presentations of operable breast cancer and to present quantitative prognostic information useful to both doctors and patients.

PATIENTS AND METHODS: A series of regionally treated breast cancer patients was analyzed to determine the likelihood and time of the appearance of clinical metastases for different clinical subgroups. Patients operated on at the University of Chicago from 1927 to 1987 for clinically regionally localized breast cancer, who received no systemic therapy as a part of their initial treatment, were included. Overall survival and distant disease-free survival in this mature series are analyzed.

RESULTS: Metastagenicity, the metastatic proclivity of a tumor, increases with both tumor size and nodal involvement. This is also true for virulence, which is the rate at which these metastases appear. Each clinical group has a cured population, even those with extensive nodal involvement. A table provides a tool for determining the proportion of risk expended in each clinical group as a function of the distant disease-free survival. Whereas the likelihood of metastasis increases with tumor size and nodal involvement, the time to their appearance decreases.

CONCLUSIONS: Breast cancer metastagenicity and virulence are heterogeneous even within clinically similar groups of operable breast cancer patients. Tumor progression is correlated with increasing tumor size and nodal involvement. Markers are needed to identify individual tumor virulence and metastagenicity.
Surveillance for Recurrent Head and Neck Cancer Using Positron Emission Tomography
Authors: Lowe Val J. , Boyd James H. , Dunphy Frank R. , Kim Han , Dunleavy T. , Collins Brian T. , Martin David , Stack Brendan C. , Hollenbeak Chris , Fletcher J.W.
Published: February 2017

PURPOSE: Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans.

PATIENTS AND METHODS: Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared.

RESULTS: Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P = .013) or PE (P = .002) in the detection of recurrence.

CONCLUSION: PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period.
Fatigue in Breast Cancer Survivors: Occurrence, Correlates, and Impact on Quality of Life
Authors: Bower Julienne E. , Ganz Patricia A. , Desmond Katherine A. , Rowland Julia H. , Meyerowitz Beth E. , Belin Thomas R.
Published: February 2017

PURPOSE: To describe the occurrence of fatigue in a large sample of breast cancer survivors relative to general population norms and to identify demographic, medical, and psychosocial characteristics of fatigued survivors.

PATIENTS AND METHODS: Breast cancer survivors in two large metropolitan areas completed standardized questionnaires as part of a survey study, including the RAND 36-item Health Survey, Center for Epidemiological Studies–Depression Scale, Breast Cancer Prevention Trial Symptom Checklist, Medical Outcomes Study Sleep Scale, and demographic and treatment-related measures.

RESULTS: On average, the level of fatigue reported by the breast cancer survivors surveyed (N = 1,957) was comparable to that of age-matched women in the general population, although the breast cancer survivors were somewhat more fatigued than a more demographically similar reference group. Approximately one third of the breast cancer survivors assessed reported more severe fatigue, which was associated with significantly higher levels of depression, pain, and sleep disturbance. In addition, fatigued women were more bothered by menopausal symptoms and were somewhat more likely to have received chemotherapy (with or without radiation therapy) than nonfatigued women. In multivariate analyses, depression and pain emerged as the strongest predictors of fatigue.

CONCLUSION: Although the majority of breast cancer survivors in this large and diverse sample did not experience heightened levels of fatigue relative to women in the general population, there was a subgroup of survivors who did report more severe and persistent fatigue. We identified characteristics of these women that may be helpful in elucidating the mechanisms underlying fatigue in this population, as well as directing intervention efforts.
Predictive Role of Interphase Cytogenetics for Survival of Patients With Multiple Myeloma
Authors: Königsberg Robert , Zojer Niklas , Ackermann Jutta , Krömer Elisabeth , Kittler Harald , Fritz Elke , Kaufmann Hannes , Nösslinger Thomas , Riedl Lucia , Gisslinger Heinz , Jäger Ulrich , Simonitsch Ingrid , Heinz Renate , Ludwig Heinz , Huber Heinz , Drach Johannes
Published: February 2017

PURPOSE: Recent metaphase cytogenetic studies suggested that specific chromosomal abnormalities are of prognostic significance in patients with multiple myeloma (MM). Because the true incidence of chromosomal abnormalities in MM is much higher than that detected by metaphase analysis, we used interphase fluorescence in situ hybridization (FISH) to determine the prognostic value of specific chromosomal aberrations.

PATIENTS AND METHODS: Bone marrow plasma cells from 89 previously untreated patients with MM were studied consecutively by FISH to detect the deletions of 13q14, 17p13, and 11q and the presence of t(11;14)(q13;q32). FISH results were analyzed in the context of clinical parameters (response to treatment and survival after conventional-dose chemotherapy), and a multivariate analysis of prognostic factors was performed.

RESULTS: By FISH, the deletion of 13q14 occurred in 40 patients (44.9%), deletion of 17p13 in 22 (24.7%), and 11q abnormalities in 14 (15.7%; seven with t(11;14)). Deletions of 13q14 and 17p13 were associated with poor response to induction treatment (46.9% v 77.3% in those without deletions, P = .006 and 40.0% v 73.2%, P = .008, respectively) and short median overall survival (OS) time (24.2 v 88.1 months, P = .008 and 16.2 v 51.3 months, P = .008, respectively). Short median OS time was also observed for patients with 11q abnormalities (13.1 v 41.6 months, P = .02). According to the number of unfavorable cytogenetic features (deletion of 13q14, deletion of 17p13, and aberrations of 11q) that were present in each patient (0 v 1 v 2 or 3), patients with significantly different OS times could be discriminated from one another (102.4 v 29.6 v 13.9 months, P < .001, respectively).

CONCLUSION: For patients with MM who were treated with conventional-dose chemotherapy, interphase FISH for 13q14, 17p13, and 11q provides prognostically relevant information in addition to that provided by standard prognostic factors. This observation may be considered for risk-adapted stratifications of MM patients in future clinical trials.