bluuebunny/crossref_metadata_2025 huggingface dataset:
Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1-positive or BRCA2-positive patients.
Authors: Grann V R , Panageas K S , Whang W , Antman K H , Neugut A I
Published: February 2017

PURPOSE

Young Ashkenazi Jewish women or those from high-risk families who test positive for BRCA1 or BRCA2 mutant genes have a significant risk of developing breast or ovarian cancer by the age of 70 years. Many question whether they should have prophylactic surgical procedures, ie, bilateral mastectomy and/or oophorectomy.

METHODS

A Markov model was developed to determine the survival, quality of life, and cost-effectiveness of prophylactic surgical procedures. The probabilities of developing breast and ovarian cancer were based on literature review among women with the BRCA1 or BRCA2 gene and mortality rates were determined from Surveillance, Epidemiology, and End Results (SEER) data for 1973 to 1992. The costs for hospital and ambulatory care were estimated from Health Care Financing Administration (HCFA) payments in 1995, supplemented by managed care and fee-for-service data. Utility measures for quality-adjusted life-years (QALYs) were explicitly determined using the time-trade off method. Estimated risks for breast and ovarian cancer after prophylactic surgeries were obtained from the literature.

RESULTS

For a 30-year-old woman, according to her cancer risks, prophylactic oophorectomy improved survival by 0.4 to 2.6 years; mastectomy, by 2.8 to 3.4 years; and mastectomy and oophorectomy, by 3.3 to 6.0 years over surveillance. The QALYs saved were 0.5 for oophorectomy and 1.9 for the combined procedures in the high-risk model. Prophylactic surgeries were cost-effective compared with surveillance for years of life saved, but not for QALYs.

CONCLUSION

Among women who test positive for a BRCA1 or BRCA2 gene mutation, prophylactic surgery at a young age substantially improves survival, but unless genetic risk of cancer is high, provides no benefit for quality of life. Prophylactic surgery is cost-effective for years of life saved compared with other medical interventions that are deemed cost-effective.
Alternative and complementary therapy use in pediatric oncology patients in British Columbia: prevalence and reasons for use and nonuse.
Authors: Fernandez C V , Stutzer C A , MacWilliam L , Fryer C
Published: February 2017

PURPOSE

Alternative and complementary therapies are infrequently studied in pediatric populations. We performed a population-based survey to aid health care workers in identifying and counseling parents who may use these remedies.

PATIENTS AND METHODS

We retrospectively surveyed the parents of 583 pediatric patients diagnosed with cancer in British Columbia between 1989 and 1995. Prevalence and factors that influence the use and nonuse of alternative and complementary therapies were estimated.

RESULTS

Alternative and complementary therapies were used by 42% of 366 respondents. Herbal teas, plant extracts, and therapeutic vitamins were the most commonly used alternative therapies. Relaxation/imagery strategies, massage, and therapeutic touch were the most commonly used complementary techniques. Factors that influenced the use of alternative/complementary therapies were prior use (chi2 = 60.0, P < .0001), prior positive attitude towards these remedies (chi2 = 41.6, P < .0001), soliciting information from family and friends (chi2 = 70.5, P < .0001) or from alternative care givers (chi2 = 58.7, P < .0001), high risk of death at diagnosis (chi2 = 9.6, P < .002), and advanced education of the father (chi2 = 7.4, P < .006) or mother (chi2 = 8.6, P < .003). Parents who used alternative/complementary therapies did so in conjunction with conventional medicine (98%). Lack of knowledge and fear of interference with conventional therapies were the most common reasons cited for nonuse. No parent believed that the quality of life of their child deteriorated due to the use of alternative/complementary therapies.

CONCLUSION

Alternative and complementary therapy use in pediatric oncology patients is common. Factors have been identified that may be associated with undertaking their use.
No long-term increase in cardiac-related mortality after breast-conserving surgery and radiation therapy using modern techniques.
Authors: Nixon A J , Manola J , Gelman R , Bornstein B , Abner A , Hetelekidis S , Recht A , Harris J R
Published: February 2017

PURPOSE

To determine whether left-breast irradiation using modern techniques after breast-conserving surgery leads to an increased risk of cardiac-related mortality.

METHODS

Between 1968 and 1986, 1,624 patients were treated for unilateral stage I or II breast cancer at the Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA, with conservative surgery and breast irradiation. Seven hundred forty-five patients with a potential follow-up of at least 12 years were analyzed. Clinical, pathologic, and treatment characteristics were compared between the 365 patients (49%) who received left-sided irradiation and the 380 patients (51%) who received right-sided irradiation. The relationship between left-sided breast irradiation and the risk of nonbreast cancer- and cardiac-related mortality was examined.

RESULTS

There was no significant difference in the distribution of clinical, pathologic, or treatment characteristics between the two groups, with the exception of a small difference in pathologic tumor size (medians, left, 2.0 cm, right, 1.5 cm; P = .007). At 12 years, a majority of patients still were alive. Slightly more patients with left-sided tumors had died of breast cancer (31% v 27%; P = NS). Equivalent proportions from each group died of nonbreast cancer causes (11%), including nine patients (2%) from each group who died from cardiac causes. The risk of cardiac mortality did not increase as time after treatment increased for patients who received left-sided irradiation compared with right-sided irradiation. A model that controlled for clinical, pathologic, and treatment differences showed no significant increase in any category of cause of death (breast, cardiac, or other) for patients who received left-sided irradiation.

CONCLUSION

These results suggest that modern breast radiotherapy is not associated with an increased risk of cardiac-related mortality within at least the first 12 years after treatment.
Carboplatin plus vinorelbine, a new well-tolerated and active regimen for the treatment of extensive-stage small-cell lung cancer: a phase II study. Gruppo Oncologico Centro-Sud-Isole.
Authors: Gridelli C , Perrone F , Ianniello G P , Brancaccio L , Iaffaioli R V , Curcio C , D'Aprile M , Cioffi R , Cigolari S , Rossi A , Palazzolo G , Veltri E , Pergola M , De Placido S , Gallo C , Monfardini S , Bianco A R
Published: February 2017

PURPOSE

To evaluate the activity and toxicity of the combination carboplatin plus vinorelbine in extensive small-cell lung cancer (SCLC).

PATIENTS AND METHODS

A two-stage optimal Simon design was applied. To proceed after the first stage, responses from 8 of 11 treated patients were needed. Overall, 31 responses of 43 treated patients were required to comply with the design parameters. Inclusion criteria were cytohistologically proven SCLC; extensive disease; age of 70 years or less; Eastern Cooperative Oncology group performance status (ps ECOG) of 2 or less; normal cardiac, hepatic, renal, and bone marrow functions; and no previous chemotherapy. Patients were staged by physical examination; biochemistry; chest radiograph; brain, thoracic; and abdominal computed tomographic (CT) scans, and bone scan. All patients received carboplatin 300 mg/m2 intravenously (i.v.) day 1 and vinorelbine 25 mg/m2 i.v. on days 1 and 8 every 4 weeks up to six cycles. Of 43 enrolled patients, 36 were men and 7 women, with a median age of 63 years (range, 46 to 70 years).

RESULTS

All patients were assessable for response and toxicity. We observed 32 (74%) objective responses, with 23% complete responses. Median time to progression was 25 weeks, and median survival was 37 weeks. The treatment was well tolerated. The reported main toxicities were leukopenia grade 3 in 21% of patients and grade 4 in 5% of patients, anemia grade 2 in 11% of patients and grade 3 in 2% of patients, and thrombocytopenia grade 3 in 7% of patients.

CONCLUSION

These data show that carboplatin plus vinorelbine is an active and well-tolerated regimen in extensive SCLC. In view of the activity, low toxicity, and ease of administration, it may be a reasonable alternative to more toxic cisplatin-containing regimens.
Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study.
Authors: Reichardt P , Tilgner J , Hohenberger P , Dörken B
Published: February 2017

PURPOSE

To evaluate the feasibility and toxicity of the combination of full-dose epirubicin (EPI) and high-dose ifosfamide (IFO) with granulocyte colony-stimulating factor (G-CSF) support and to determine the clinical efficacy in terms of response and impact on survival.

PATIENTS AND METHODS

Forty-six consecutive, previously untreated patients with locally advanced or metastatic high-grade soft tissue sarcomas were treated with IFO 2.5 g/m2/d as a continuous infusion on days 1 to 5 and EPI 45 mg/m2/d as a continuous infusion on days 2 and 3 every 3 weeks. G-CSF 5 microg/kg/d subcutaneously (s.c.) was given on days 6 to 15 or until recovery of leukocytes after all cycles. Response evaluation was performed every two cycles and responding patients were treated with up to six cycles. All patients were evaluated for resectability of residual local or metastatic disease and underwent surgery if possible.

RESULTS

All patients experienced grade 3 or 4 myelosuppression. Other toxicities were mild. The overall response rate was 52%, with a complete remission (CR) rate of 22% after chemotherapy alone. Eight additional patients were rendered free of tumor (no evidence of disease [NED]) by surgical procedures. The median overall survival of all patients is 24 months. The CR/NED patients (39%) have a significantly superior survival time compared with all other patients. Thirteen of these 18 patients (72%) are alive, nine free of tumor, with a median follow-up time of 33 months.

CONCLUSION

This dose-intensive combination chemotherapy is toxic but feasible and produced a high number of partial remissions (PRs) and especially CRs, which resulted in prolonged survival.
Back-up bone marrow is frequently ineffective in patients with poor peripheral-blood stem-cell mobilization.
Authors: Watts M J , Sullivan A M , Leverett D , Peniket A J , Perry A R , Williams C D , Devereux S , Goldstone A H , Linch D C
Published: February 2017

PURPOSE

To assess hematologic recovery and procedure-related mortality in patients who received high-dose therapy with stem-cell support, in whom the peripheral-blood stem-cell (PBSC) collection fails (CD34+ cells < 1 x 10(6)/kg). The predictive value of granulocyte-monocyte colony-forming cell (GM-CFC) measurements and the value of bone marrow obtained after PBSC collection failure was assessed.

PATIENTS AND METHODS

The study group comprised 324 consecutive patients mobilized with granulocyte colony-stimulating factor (G-CSF) and cyclophosphamide (273 patients), G-CSF with other chemotherapy (37 patients), and G-CSF alone (14 patients). Between one and four aphereses were performed.

RESULTS

In 51 of 324 patients, there was failure to obtain 1 x 10(6)/kg CD34+ cells. Twenty-three patients had greater than 1 x 10(5)/kg GM-CFC; 22 patients proceeded to high-dose therapy. Neutrophil recovery occurred within 21 days, but platelet independence was delayed (> 28 days) in eight patients. Of 28 patients with less than 1 x 10(5)/kg GM-CFC, six received high-dose therapy with PBSC alone and five had delayed engraftment. Twelve patients with less than 1 x 10(5)/kg GM-CFC received high-dose therapy supported by bone marrow collected after PBSC collection failure. Eleven patients were assessable for engraftment; four patients had slow (> 21 days) or delayed (> 28 days) neutrophil recovery and eight patients had delayed platelet recovery. In the group of patients who received less than 1 x 10(5)/kg GM-CFC, there were five procedure-related deaths.

CONCLUSION

This study shows that delayed hematologic recovery is frequent if less than 1 x 10(6)/kg CD34+ cells are infused after high-dose therapy, particularly with GM-CFC less than 1 x 10(5)/kg. The procedure-related mortality in this latter group is high. In most patients whose PBSC collection contains less than 1 x 10(5)/kg GM-CFC, the use of bone marrow cells does not improve engraftment, which suggests that poor PBSC mobilization usually indicates poor marrow function.
Cancer in human immunodeficiency virus-infected children: a case series from the Children's Cancer Group and the National Cancer Institute.
Authors: Granovsky M O , Mueller B U , Nicholson H S , Rosenberg P S , Rabkin C S
Published: February 2017

PURPOSE

To describe the spectrum of malignancies in human immunodeficiency virus (HIV)-infected children and the clinical outcome of patients with these tumors.

METHODS

We retrospectively surveyed the Children's Cancer Group (CCG) and the National Cancer Institute (NCI) for cases of cancer that occurred between July 1982 and February 1997 in children who were HIV seropositive before or at the time of cancer diagnosis. We used Kaplan-Meier survivorship curves, hazard function estimates, and Cox proportional hazards models to evaluate survival.

RESULTS

Sixty-four children (39 boys, 25 girls) with 65 tumors were reported. Thirty-seven children (58%) acquired HIV infection vertically (median age at cancer diagnosis, 4.3 years); 22 children (34%) acquired HIV through transfusion of blood or blood products (median age at cancer diagnosis, 13.4 years). Forty-two children (65%) had non-Hodgkin's lymphoma (NHL). Eleven children (17%) had leiomyosarcomas (or leiomyomas), which are otherwise exceptionally rare in children. Other malignancies included acute leukemia (five children), Kaposi's sarcoma (KS; three children), Hodgkin's disease (two children), vaginal carcinoma in situ (one child), and tracheal neuroendocrine carcinoma (one child). Median survival after NHL diagnosis was 6 months (range, 1 day to 89 months) and after leiomyosarcoma was 12 months (range, 10 days to 19 months). The average monthly death rate after NHL diagnosis was 12% in the first 6 months, which decreased to about 2% thereafter. In contrast, the monthly death rate after leiomyosarcoma diagnosis increased from 5% in the first 6 months to about 20% thereafter.

CONCLUSION

After NHL, leiomyosarcoma is the second leading cancer in children with HIV infection. Both cancers have high mortality rates; improved outcome for NHL, in particular, may depend on earlier diagnosis and therapy.
Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium 99m-labeled totally human monoclonal antibody 88BV59: results of pivotal, phase III multicenter studies.
Authors: Serafini A N , Klein J L , Wolff B G , Baum R , Chetanneau A , Pecking A , Fischman A J , Hoover H C , Wynant G E , Subramanian R , Goroff D K , Hanna M G
Published: February 2017

PURPOSE

To assess the performance and potential clinical impact of a totally human monoclonal antibody, 88BV59 (HumaSPECT) (INTRACEL, Corp, Rockville, MD), in 202 assessable presurgical patients with recurrent, metastatic, or occult colorectal cancer.

METHODS

88BV59, labeled with technetium Tc 99m (99mTc) (HumaSPECT-Tc), was injected intravenously, and planar and single photon emission tomography (SPECT) images were obtained 14 to 20 hours postinjection. Surgical and pathologic verification of tumor were used as the standard against which the performance of HumaSPECT-Tc imaging and computed tomography (CT) analysis were evaluated.

RESULTS

All patients entered onto the recurrent disease study had at least one tumor site defined on CT. The sensitivity of HumaSPECT-Tc in those CT-positive patients was 87%. The specificity of HumaSPECT-Tc was 57% compared with 17% for CT and the difference was statistically significant (P < .001). The diagnostic information provided by HumaSPECT-Tc significantly (P < .001) improved the accuracy of the identification of resectable and nonresectable disease over that of CT (80% v 62%). HumaSPECT-Tc scans resulted in a significant (P < .001) reduction versus CT in terms of the proportion of patients understaged (27% v 41%) and overstaged (4% v 26%). In patients with occult disease (increasing carcinoembryonic antigen [CEA] titer, negative diagnostic work-up, negative CT), HumaSPECT-Tc correctly identified disease in 15 of 22 (68%) patients. HumaSPECT-Tc images provided additional clinical data that would have affected patient management decisions in 40 of 202 (19.8%) patients. In 365 patients who received 88BV59, only a single detectable human anti-human antibody (HAHA) response (90 ng/mL) at 9 weeks postinfusion was observed.

CONCLUSION

HumaSPECT-Tc can provide important and accurate information about the presence and location of disease in patients with a high clinical suspicion of metastatic or recurrent colorectal cancer and either positive (known disease) or negative (occult disease) CT scans.
Rapid hematopoietic recovery after multicycle high-dose chemotherapy: enhancement of filgrastim-induced progenitor-cell mobilization by recombinant human stem-cell factor.
Authors: Basser R L , To L B , Begley C G , Maher D , Juttner C , Cebon J , Mansfield R , Olver I , Duggan G , Szer J , Collins J , Schwartz B , Marty J , Menchaca D , Sheridan W P , Fox R M , Green M D
Published: February 2017

PURPOSE

To assess the mobilization potential and safety of recombinant human stem-cell factor (SCF) when coadministered with filgrastim to untreated women with poor-prognosis breast cancer.

PATIENTS AND METHODS

Eligible women had breast cancer with 10 or more positive axillary nodes, or estrogen receptor-negative tumor with 4 positive nodes, or stage III disease. Patients were randomized to receive SCF plus filgrastim or filgrastim alone. Filgrastim 12 microg/kg daily was administered for 6 days by continuous subcutaneous infusion. SCF was administered by daily subcutaneous injection at 5, 10, or 15 microg/kg concurrent with filgrastim for 7 days, or 10 microg/kg daily starting 3 days before filgrastim for a total of 10 days (SCF pretreatment). Apheresis was performed on days 5, 6, and 7 of filgrastim administration. Patients then had three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2 every 28 days, each supported by one third of the apheresis product.

RESULTS

Sixty-two women were treated. Greater yields occurred in patients who received SCF 10 microg/kg daily plus filgastim than those who received filgrastim alone (P=.013 for CD34+ cells; P=.07 for granulocyte-macrophage colony-forming cells [GM-CFCs]). The difference was more marked with SCF-pretreatment than concurrent SCF. Fewer aphereses were required to reach the predetermined target of peripheral-blood progenitor/stem cells (PBPCs) in women who received SCF. SCF was generally well tolerated. Hematologic recovery was rapid after each of the three cycles of chemotherapy. There was no difference in recovery between the different treatment groups.

CONCLUSION

Mobilization of PBPCs by filgrastim is significantly enhanced by coadministration of SCF, and commencing SCF before filgrastim can optimize this effect. SCF has the potential to reduce the number of aphereses required to collect a target number of PBPCs.
Clinical outcome in diffuse large B-cell lymphoma is dependent on the relationship between different cell-cycle regulator proteins.
Authors: Sanchez E , Chacon I , Plaza M M , Muñoz E , Cruz M A , Martinez B , Lopez L , Martinez-Montero J C , Orradre J L , Saez A I , Garcia J F , Piris M A
Published: February 2017

PURPOSE

The goal of this work was to perform a comprehensive exploration of the relationship between the clinical outcome of diffuse large B-cell lymphoma (DLBCL) and the expression of a panel of tumor suppressor and oncogenic proteins, which includes some cell-cycle regulator proteins involved in the p53 pathway.

PATIENTS AND METHODS

To this end, we collected the clinical data of 141 patients with DLBCL and immunohistochemically analyzed diagnostic tumoral tissue from each patient for the presence of Ki67 (MIB1, Immuno-tech, Marseille, France), bcl2, p53, p21/WAF1, MDM2, and retinoblastoma (Rb) proteins.

RESULTS

The results show that several proteins are associated with some of the clinical traits analyzed. Multivariate analysis showed that an extended overall survival (OS) time was associated with low growth fraction, high Rb protein, and low MDM2 expression, as well as with known clinical parameters. The probability of inducing a complete remission (CR) was only associated with clinical parameters, although univariate study showed that a low growth fraction was associated with a higher probability of inducing a CR. Univariate study of disease-free survival (DFS) showed that tumors with high bcl2 expression and nodal origin have a shorter DFS time, although multivariate study only confirmed the adverse effect of bcl2 expression.

CONCLUSION

Taking all these results into consideration, it seems that although the overall outcome for patients with DLBCL is decided by a combination of different clinical and biologic variables, the expression of some of these cell-cycle regulator proteins appears to be specifically associated with the different clinical features of tumors.
Late effects in long-term survivors of high-grade non-Hodgkin's lymphomas.
Authors: Haddy T B , Adde M A , McCalla J , Domanski M J , Datiles M , Meehan S C , Pikus A , Shad A T , Valdez I , Lopez Vivino L , Magrath I T
Published: February 2017

PURPOSE

To evaluate long-term survivors of high-grade non-Hodgkin's lymphomas (NHLs) for late effects and to attempt to assess the relative contributions of the primary treatment modalities to these late effects.

PATIENTS AND METHODS

Of 103 young survivors followed up for 1 to 20 years, 74 patients were interviewed and underwent various investigations, and an additional 12 patients were interviewed only. Of the 86 patients, 65 had previously suffered from small non-cleaved-cell lymphoma, 16 from lymphoblastic lymphoma, and five from large-cell lymphoma.

RESULTS

Left ventricular dysfunction was identified in eight of 57 (14.0%) patients who had received doxorubicin (DOX) in doses greater than 200 mg/m2, of whom four were symptomatic and four were asymptomatic. A ninth patient required a pacemaker. Of the 86 patients, 23 (26.7%) reported pregnancies, 18 of whom had 30 children. Two of the 86 (2.3%) patients developed second cancers. Other major late effects included posttransfusion viral hepatitis, eight patients; CNS toxicity, two patients; endocrine impairment, 14 patients; vitamin B12 deficiency, two patients; esophageal stricture, one patient; urinary tract problems, two patients; and musculoskeletal defects, three patients. Major late effects occurred in 11 of 21 (52.4%) patients who had received radiation as well as chemotherapy, eight of 22 (36.4%) patients who had surgical resections as well as chemotherapy, and 17 of 74 (23.0%) patients who had received chemotherapy alone.

CONCLUSION

The predominant major late effects observed were late cardiac toxicity related to DOX therapy and hepatitis C virus infection that presumably resulted from blood product transfusions administered before the introduction of screening for the hepatitis C virus. Fertility was not greatly impaired, and second malignancies were uncommon. No patient had clinically significant impairment of growth. Radiation appeared to increase the likelihood of late effects.
bcl-2 protein expression in primary cutaneous large B-cell lymphoma is site-related.
Authors: Geelen F A , Vermeer M H , Meijer C J , Van der Putte S C , Kerkhof E , Kluin P M , Willemze R
Published: February 2017

PURPOSE

Primary cutaneous large B-cell lymphoma (PCLBCL) that presents on the leg has recently been recognized as a distinct disease entity. These lymphomas have a reduced disease-free survival and a worse prognosis as compared with the more common, morphologically similar PCLBCL that present on the head or trunk. Studies in noncutaneous diffuse large B-cell lymphomas suggest a relationship between the expression of bcl-2 protein and clinical behavior. In the present study, we investigated whether these two groups of PCLBCL differ in the expression of bcl-2 protein and the presence of t(4;18), known as one of the causes of bcl-2 overexpression.

PATIENTS AND METHODS

Paraffin sections from pretreatment biopsies of 14 PCLBCLs of the head or trunk and nine PCLBCLs of the legs were investigated for expression of bcl-2 protein using immunohistochemistry, and for the presence of the 14;18 translocation using polymerase chain reaction (PCR) amplification with primers against both the major breakpoint region (mbr) and the minor cluster region (mcr) of bcl-2. For reasons of comparison, nine secondary cutaneous large B-cell lymphomas (SCLBCLs) were also studied.

RESULTS

Expression of bcl-2 protein was found in all nine PCLBCLs of the leg and in all nine SCLBCLs, but not in any of the 14 PCLBCLs on the head and trunk. The t(14;18) was only detected in two of seven SCLBCLs, but not in the five PCLBCLs of the leg or the eight PCLBCLs on the head or trunk studied.

CONCLUSION

The striking differences in bcl-2 expression between PCLBCL of the head or trunk and PCLBCL on the leg suggest that bcl-2 expression is site-related and may contribute to the different clinical behavior between these two groups of lymphomas. In addition, they underscore that PCLBCL on the head and trunk and PCLBCL on the leg are distinct disease entities, as recently recognized in the European Organization for Research and Treatment of Cancer (EORTC) classification for primary cutaneous lymphomas.
Unknown primary tumors metastatic to liver.
Authors: Ayoub J P , Hess K R , Abbruzzese M C , Lenzi R , Raber M N , Abbruzzese J L
Published: February 2017

PURPOSE

The objectives of this study were to identify prognostic factors for unknown primary tumor (UPT) patients with hepatic metastases, determine the common primary tumors identified, assess the yield of specific diagnostic studies, and evaluate the impact of therapy on survival.

PATIENTS AND METHODS

The 1,522 patients analyzed were referred from January 1, 1987 through June 30, 1995. Clinical data from these patients were entered into a computerized database for storage, retrieval, and analysis. Survival was measured from the time of diagnosis; survival distribution was estimated by the product limit method. Multivariate survival analyses were performed by proportional hazards regression.

RESULTS

Five hundred UPT patients had liver metastases. Primary tumors, usually lung, colorectal, or pancreatic neoplasms, were identified in 135 patients (27%). The remaining 365 unknown primary carcinoma (UPC) patients with liver involvement had a higher death rate than those without liver involvement (hazards ratio, 1.63; P < .0001). Neuroendocrine carcinoma patients had a lower death rate than patients without this histology (hazards ratio, 0.29; (P < .0001). Two hundred sixteen of 365 patients with UPC and liver metastases received chemotherapy. Chemotherapy-treated patients had a lower death rate than those who were not treated with chemotherapy (hazards ratio, 0.52; P < .0001). The effect of chemotherapy was most pronounced in patients with adenocarcinoma.

CONCLUSION

Hepatic metastases in UPC patients portend a generally poor prognosis. However, subsets of patients with more favorable outcomes can be identified by available clinical and pathologic data. Chemotherapy may be beneficial for the large subset of UPC patients with adenocarcinoma that involves the liver.
Analytical decision model for the cost-effective management of solitary pulmonary nodules.
Authors: Gambhir S S , Shepherd J E , Shah B D , Hart E , Hoh C K , Valk P E , Emi T , Phelps M E
Published: February 2017

PURPOSE AND METHODS

Multiple strategies are currently being used to manage patients who present with indeterminate solitary pulmonary nodules (SPN). We have used decision-analysis models to assess the cost-effectiveness of various strategies for the diagnosis and management of SPN. Four decision strategies were compared: a wait and watch strategy, a surgery strategy, a computed tomography (CT)-based strategy, and a CT-plus-positron emission tomography (PET) strategy. An incremental cost-effectiveness ratio (ICER) was used to compare all strategies to the wait and watch strategy.

RESULTS

A CT-plus-PET strategy was the most cost-effective over a large pretest likelihood (probability of having a malignant nodule), with a range of 0.12 to 0.69. Furthermore, within this likelihood range, the potential cost savings of using the CT-plus-PET strategy over the CT strategy ranged from $91 to $2,200 per patient. This translates to a yearly national savings of approximately $62.7 million.

CONCLUSION

Decision-analysis modeling indicates the potential cost-effectiveness of [18F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in the management of SPN. Furthermore, the decision trees developed can be used to model various features of the management of SPN, including modeling the cost-effectiveness of other newly emerging technologies.
Tumor lysis syndrome: an uncommon complication of fludarabine therapy of chronic lymphocytic leukemia.
Authors: Cheson B D , Frame J N , Vena D , Quashu N , Sorensen J M
Published: February 2017

PURPOSE

To quantify the incidence and severity of tumor lysis syndrome (TLS) as a consequence of fludarabine therapy in patients with advanced chronic lymphocytic leukemia (CLL).

PATIENTS AND METHODS

A retrospective review and questionnaire follow-up of clinical and laboratory data were performed on patients with intermediate or high-risk CLL on the National Cancer Institute Group C protocol or special exception mechanisms, or phase II trials of fludarabine, for whom adverse drug reports of TLS were available. Fludarabine was administered at a dose of 20 to 40 mg/m2 per day for 5 days at monthly intervals.

RESULTS

Among the 6,137 patients, TLS was suspected in 26 (0.42%), with clinical and laboratory features consistent with TLS present in 20 (0.33%). Prophylaxis against TLS had been administered to 60% of these patients. Clinical or laboratory features were similar to patients who did not develop TLS. Of the patients with TLS, 90% had high-risk CLL, 60 months of prior disease duration, with a median pretreatment WBC of 109 x 10(9)/L, two prior regimens, lymphadenopathy in 89%, splenomegaly and/or hepatomegaly in 90%. TLS developed on approximately day 7 and lasted a median of 9.5 days. Dialysis was required in 30% during the TLS episode; 20% of patients died during cycle one of fludarabine therapy with renal failure, and another 20% died of infection or congestive heart failure. Six patients were retreated with fludarabine without recurrent TLS.

CONCLUSION

TLS after fludarabine therapy is extremely uncommon, but may be associated with significant morbidity and mortality.
Costs of blood transfusion: a process-flow analysis.
Authors: Cantor S B , Hudson D V , Lichtiger B , Rubenstein E B
Published: February 2017

PURPOSE

To determine the cost of transfusing 2 units (U) of packed RBCs at a comprehensive cancer center.

METHODS

We performed a process-flow analysis to identify all costs of transfusing 2 U of allogeneic packed RBCs on an outpatient basis to patients with either (1) solid tumor who did not undergo bone marrow transplantation (BMT), (2) solid tumor who underwent BMT, (3) hematologic malignancy who did not undergo BMT, (4) hematologic malignancy who underwent allogeneic BMT, or (5) hematologic malignancy who underwent autologous BMT. We conducted structured interviews to determine the personnel time used and physical resources necessary at all steps of the transfusion process.

RESULTS

The mean cost of a 2-U transfusion of allogeneic packed RBCs was $548, $565, $569, $569, and $566 for patients with non-BMT solid tumor, BMT solid tumor, non-BMT hematologic malignancy, allogeneic BMT hematologic malignancy, and autologous BMT hematologic malignancy, respectively. Sensitivity analysis showed that total transfusion costs were sensitive to variations in the amount of clinician compensation and overhead costs, but were relatively insensitive to reasonable variations in the direct costs of blood tests and the blood itself, or the probability or extent of transfusion reaction.

CONCLUSION

The costs of the transfusion of packed RBCs are greater than previously analyzed, particularly in the cancer care setting.
Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk.
Authors: Frank T S , Manley S A , Olopade O I , Cummings S , Garber J E , Bernhardt B , Antman K , Russo D , Wood M E , Mullineau L , Isaacs C , Peshkin B , Buys S , Venne V , Rowley P T , Loader S , Offit K , Robson M , Hampel H , Brener D , Winer E P , Clark S , Weber B , Strong L C , Thomas A
Published: February 2017

PURPOSE

Previous studies of mutations in BRCA1 or BRCA2 have used detection methods that may underestimate the actual frequency of mutations and have analyzed women using heterogeneous criteria for risk of hereditary cancer.

PATIENTS AND METHODS

A total of 238 women with breast cancer before age 50 or ovarian cancer at any age and at least one first- or second-degree relative with either diagnosis underwent sequence analysis of BRCA1 followed by analysis of BRCA2 (except for 27 women who declined analysis of BRCA2 after a deleterious mutation was discovered in BRCA1). Results were correlated with personal and family history of malignancy.

RESULTS

Deleterious mutations were identified in 94 (39%) women, including 59 of 117 (50%) from families with ovarian cancer and 35 of 121 (29%) from families without ovarian cancer. Mutations were identified in 14 of 70 (20%) women with just one other relative who developed breast cancer before age 50. In women with breast cancer, mutations in BRCA1 and BRCA2 were associated with a 10-fold increased risk of subsequent ovarian carcinoma (P = .005).

CONCLUSION

Because mutations in BRCA1 and BRCA2 in women with breast cancer are associated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data.
Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor.
Authors: Loehrer P J , Gonin R , Nichols C R , Weathers T , Einhorn L H
Published: February 2017

PURPOSE

This study was designed to assess the effectiveness of vinblastine, ifosfamide, and cisplatin (VeIP) as second-line therapy in patients with recurrent germ cell tumors with previous treatment with cisplatin plus etoposide, usually in combination with bleomycin.

PATIENTS AND METHODS

From July 1984 through December 1989, 135 patients with progressive, disseminated germ cell tumors after cisplatin-etoposide-based combination therapy induction chemotherapy were treated with VeIP. Patients who progressed within 3 weeks of previous cisplatin therapy were not eligible. Progression was documented by biopsy or increasing serum markers. No exclusion was made on the basis of metastatic site or performance status. The dosages were vinblastine 0.11 mg/kg/d (days 1 and 2), ifosfamide 1.2 gm/m2/d (days 1 through 5), and cisplatin 20 mg/m2/d (days 1 through 5), with courses repeated every 21 days for four cycles.

RESULTS

Sixty-seven (49.6%) patients achieved a disease-free status after chemotherapy with or without surgical resection of residual carcinoma or teratoma. Overall, 42 (32%) patients are alive and 32 (23.7%) are continuously free of disease. None of the 32 patients with nonseminomatous extragonadal tumors are disease-free compared with 30 of 100 patients with gonadal primaries. Two of three extragonadal seminomas are continuously disease-free.

CONCLUSION

VeIP is capable of producing durable complete remissions in patients with disseminated germ cell cancer who relapse after cisplatin-etoposide-based induction therapy. Long-term disease-free survival is not seen in those patients with extragonadal nonseminomatous germ cell tumors.
Positron emission tomography with 5-hydroxytryprophan in neuroendocrine tumors.
Authors: Orlefors H , Sundin A , Ahlström H , Bjurling P , Bergström M , Lilja A , Långström B , Oberg K , Eriksson B
Published: February 2017

PURPOSE

Carcinoid tumors, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP). We have evaluated the usefulness of positron emission tomography (PET) with carbon-11-labeled 5-HTP in the diagnosis and treatment follow-up evaluation of patients with neuroendocrine tumors.

PATIENTS AND METHODS

PET using 11C-labeled 5-HTP was compared with computed tomography (CT) in 18 patients (14 midgut, one foregut, one hindgut carcinoid, and two endocrine pancreatic tumors [EPT]). In addition, 10 of 18 patients were monitored with PET examinations during treatment.

RESULTS

All 18 patients, including two with normal urinary 5-hydroxyindole acetic acid (U-5-HIAA), had increased uptake of 11C-labeled 5-HTP in tumorous tissue as compared with normal tissue. Liver metastases, as well as lymph node, pleural, and skeletal metastases, showed enhanced 5-HTP uptake and PET could detect more lesions than CT in 10 patients and equal numbers in the others. Tumor visibility was better for PET than for CT due to the high and selective uptake of 5-HTP with a high tumor-to-background ratio. Binding studies indicated an irreversible trapping of 5-HTP in the tumors. Linear regression analyses showed a clear correlation (r = .907) between changes in U-5-HIAA and changes in the transport rate constant for 5-HTP during treatment.

CONCLUSION

PET with 11C-labeled 5-HTP demonstrated high uptake in neuroendocrine gastrointestinal tumors and thereby allowed improved visualization compared with CT. The in vivo data on regional tumor metabolism, as expressed in 11C-5-HTP uptake and transport rate, provided additional information over conventional radiologic techniques. The close correlation between the changes in 11C-5-HTP transport rate and U-HIAA during medical treatment indicates the potential of 11C-5-HTP-PET as a means to monitor therapy.
BAX protein expression and clinical outcome in epithelial ovarian cancer.
Authors: Tai Y T , Lee S , Niloff E , Weisman C , Strobel T , Cannistra S A
Published: February 2017

PURPOSE

Expression of the pro-apoptotic protein BAX sensitizes ovarian cancer cell lines to paclitaxel in vitro by enhancing the pathway of programmed cell death. The present study was performed to determine the relationship between BAX expression and clinical outcome in 45 patients with newly diagnosed ovarian cancer.

METHODS

BAX protein expression was analyzed by immunohistochemistry, and its relationship with clinical outcome was determined. Assessment of BAX mRNA transcript levels and mutational analysis of the BAX coding region were also performed.

RESULTS

BAX protein was expressed at high levels (defined as > or = 50% of tumor cells positive) in tumor tissue from 60% of newly diagnosed patients. All patients whose tumors expressed high levels of BAX achieved a complete response (CR) to first-line chemotherapy that contained paclitaxel plus a platinum analogue, compared with 57% of patients in the low-BAX group (P = .036). After a median follow-up of 1.9 years, the median disease-free survival (DFS) of patients in the high-BAX group has not been reached, compared with a median DFS of 1.1 years for low-BAX expressors (P = .0061). BAX retained independent prognostic significance in multivariate analysis when corrected for stage and histology. BAX mRNA transcripts were easily detected in samples with low BAX protein expression, and no BAX mutations were identified.

CONCLUSION

The correlation between high BAX levels and improved clinical outcome suggests that an intact apoptotic pathway is an important determinant of chemoresponsiveness in ovarian cancer patients who receive paclitaxel.
Clinical significance of alpha-catenin, collagen IV, and Ki-67 expression in epithelial ovarian cancer.
Authors: Anttila M , Kosma V M , Ji H , Wei-Ling X , Puolakka J , Juhola M , Saarikoski S , Syrjänen K
Published: February 2017

PURPOSE

To analyze alpha-catenin and collagen IV expression in epithelial ovarian cancer with special reference to their prognostic significance and correlations with clinical and pathologic characteristics, as well as cell proliferation marker Ki-67.

PATIENTS AND METHODS

Alpha-catenin, collagen IV, and Ki-67 expression was immunohistochemically analyzed in paraffin-embedded specimens of 316 patients with epithelial ovarian cancer.

RESULTS

Alpha-catenin and collagen IV expression was not interrelated or related to International Federation of Gynecology and Obstetrics (FIGO) stage or proliferation marker Ki-67. Alpha-catenin expression was reduced (< 100%) in 50% of primary tumors. Reduced alpha-catenin and collagen IV expression was directly related to high histologic grade (P < .001). In both univariate and multivariate analyses, Ki-67 proliferation significantly predicted overall survival. In the subset of 86 patients with stage I tumor, a reduced (< 100%) alpha-catenin expression approached statistical significance as a negative prognostic factor (P = .035) and retained its statistical significance in the multivariate analysis (P = .025). The low (< 30%) expression of alpha-catenin (n = 10) was a sign of inferior survival as compared with normal expression in both the univariate (P = .0107) and multivariate analyses (P = .0105).

CONCLUSION

Alpha-catenin expression seems to be a useful marker of those FIGO stage I tumors likely to run a less favorable course. The high cell proliferative activity was associated with poor survival. In the future, alpha-catenin and Ki-67 expression should be studied in a large prospective cohort that includes early-stage cancers to select the more aggressive tumors for intense early chemotherapy.
Human papillomavirus genotype as a major determinant of the course of cervical cancer.
Authors: Lombard I , Vincent-Salomon A , Validire P , Zafrani B , de la Rochefordière A , Clough K , Favre M , Pouillart P , Sastre-Garau X
Published: February 2017

PURPOSE

To determine whether the prognosis of invasive cancers of the uterine cervix is related to the type of human papillomavirus (HPV) associated with the tumor.

PATIENTS AND METHODS

Two hundred ninety-seven patients with invasive cervical cancer were prospectively registered from 1986 to 1994. HPV typing was performed on DNA extracted from frozen tumor specimens by means of Southern blot hybridization (SBH) and polymerase chain reaction (PCR) techniques. The median follow-up was 38 months.

RESULTS

HPV sequences were detected in 246 patients (83%): 150 patients had HPV16, 31 patients had HPV18, and 14 patients had one of the intermediate-oncogenic-risk HPV types (HPV31, 33, 35, 52, 58). In 51 patients, HPV type remained undetermined, and in 51 patients, no viral sequences were found. No significant associations were observed between virologic data and tumor stage or node status. The 5-year disease-free survival (DFS) rate was 100% for patients with intermediate-risk HPV-associated tumors, 58% for patients with HPV16-positive tumors, and 38% for patients with HPV18-positive tumors (P = .02). In multivariate analysis, patients with HPV18-associated tumors had a relative risk (RR) of death 2.4 times greater (95% confidence interval [CI], 1.29-4.59) than that for patients with HPV16, and 4.4 times greater (95% CI, 3.48-5.32) than that for patients with a tumor associated with a viral type different from HPV16/18.

CONCLUSION

The prognosis for invasive cancers of the uterine cervix is dependent on the oncogenic potential of the associated HPV type. HPV typing may provide a prognostic indicator for individual patients and is of potential use in defining specific therapies against HPV-harboring tumor cells.
Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients.
Authors: Bostick P J , Chatterjee S , Chi D D , Huynh K T , Giuliano A E , Cote R , Hoon D S
Published: February 2017

PURPOSE

This study was performed to evaluate the potential of specific mRNA markers to detect micrometastases by reverse-transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis of sentinel lymph nodes (SNs) and blood from patients with breast cancer.

PATIENTS AND METHODS

We assessed the specificity of carcinoembryonic antigen (CEA), cytokeratin-19 (CK-19), CK-20, gastrointestinal tumor-associated antigen-733.2 (GA733.2), and mucin-1 (MUC-1) in the blood of healthy donors (n = 13) and lymph nodes from patients without cancer (n = 3) by RT-PCR assay. The sensitivity of the RT-PCR assay for the target mRNA markers was assessed in breast cancer cell lines (n = 4), primary breast tumors (n = 8), and the frozen sections of SNs (n = 22) from 22 patients with American Joint Committee on Cancer (AJCC) stages I to IIIA breast cancer.

RESULTS

CK-20 was the only mRNA marker not detected in lymph nodes or blood from patients without cancer. Both the blood and lymph nodes from patients without cancer expressed CEA, CK-19, GA733.2, and MUC-1 mRNA. All four breast cancer cell lines and six of eight primary breast tumors expressed all five mRNA markers. Expression of mRNA by the RT-PCR assay in the frozen-section SNs (n = 12) without metastases by conventional histopathology ranged from 8% (CK-20) to 92% (GA733.2). Detection of RT-PCR cDNA products in frozen-section SNs was increased with Southern blot analysis compared with ethidium bromide gel electrophoresis (EtBr) for all mRNA markers except CK-19.

CONCLUSION

CEA, CK-19, GA733.2, and MUC-1 show no diagnostic value as mRNA markers for the detection of micrometastases by the RT-PCR assay because they are expressed in the blood and lymph nodes of patients without cancer. Further studies are needed to assess the sensitivity of CK-20 to detect micrometastases by the RT-PCR assay in the blood and frozen-section SNs of patients with breast cancer.
Aging, progression, and phenotype in breast cancer.
Authors: Heimann R , Hellman S
Published: February 2017

The malignant potential of cancer is dynamic, changing throughout the natural history of a tumor. For breast cancer, this is especially important because the clinical presentation has been altered by the increasing use of screening mammography. The varied outcomes of similarly staged patients is most consistent with breast cancer not being a homogeneous disease, but rather a spectrum of disease states that have varying capacities for growth and metastasis. Evolutionary pressures are at play in both tumor development and during the clinically apparent portion of the life of a tumor and are responsible for this spectrum of tumor heterogeneity. Required of tumors is the development of critical phenotypic attributes: growth, invasion, metastagenicity, and angiogenesis. The combination and permutation of genetic changes that result in the acquisition of these characteristics may vary, but they must result in some expression of each of these phenotypes. The expression of these attributes will differ as tumors evolve to become more adept at each of these characteristics. Recognizing tumor heterogeneity emphasizes the need to determine an individual tumor's place in the evolutionary spectrum. This may be accomplished using clinical features such as size, nuclear grade, and patient age, as well as by examining markers of angiogenesis, metastatic capacity, and proliferation. Identification of the extent of tumor progression with regard to these major tumor phenotypes should allow individual therapy to be fashioned for each patient.