bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Systemic Treatment on Local Control for Patients With Lymph Node–Negative Breast Cancer Treated With Breast-Conservation Therapy
Authors: Buchholz Thomas A. , Tucker Susan L. , Erwin Jessica , Mathur Daniel , Strom Eric A. , McNeese Marsha D. , Hortobagyi Gabriel N. , Cristofanilli Massimo , Esteva Francisco J. , Newman Lisa , Singletary S. Eva , Buzdar Aman U. , Hunt Kelly K.
Published: February 2017

PURPOSE: To determine the impact of tamoxifen and chemotherapy on local control for breast cancer patients treated with breast-conservation therapy.

PATIENTS AND METHODS: The data from 484 breast cancer patients who were treated with breast-conserving surgery and radiation were analyzed. Only patients with lymph node–negative disease were studied to provide comparative groups with a similar stage of disease and a similar competing risk for distant metastases. Actuarial local control rates of the 277 patients treated with systemic therapy (128, chemotherapy with or without tamoxifen; 149, tamoxifen alone) were compared with the rates for the 207 patients who received no systemic treatment. Only 10% of the patients had positive (2%), close (3%), or unknown margin status (5%).

RESULTS: Patients treated with systemic therapy had improved 5-year (97.5% v 89.8%) and 8-year (95.6% v 85.2%) local control rates compared with those that did not receive systemic treatment (P = .004, log-rank test). There was no statistical difference in local control between patients treated with chemotherapy and patients treated with tamoxifen alone (P = .219). Systemic treatment, margin status, young patient age, estrogen and progesterone receptor status, and primary tumor size were analyzed in a Cox regression analysis. The use of systemic treatment was the most powerful predictor of local control: patients who did not receive systemic treatment had a relative risk of local recurrence of 3.3 (95% confidence interval, 1.5 to 7.5; P = .004).

CONCLUSION: In this retrospective analysis, systemic therapy appears to contribute to long-term local control in patients with lymph node–negative breast cancer treated with breast-conservation therapy.
Factors Predicting the Use of Breast-Conserving Therapy in Stage I and II Breast Carcinoma
Authors: Morrow Monica , White Julia , Moughan Jennifer , Owen Jean , Pajack Thomas , Sylvester JoAnne , Frank Wilson J. , Winchester David
Published: February 2017

PURPOSE: To define patterns of care for the local therapy of stage I and II breast cancer and to identify factors used to select patients for breast-conserving therapy (BCT).

PATIENTS AND METHODS: A convenience sample of 16,643 patients with stage I and II breast cancer treated in 1994 was obtained from hospital-based tumor registries. Histologic variables were determined from original pathology reports.

RESULTS: BCT was performed in 42.6% of patients. Multivariate analysis demonstrated that living in the Northeast United States (odds ratio [OR], 2.48; 95% confidence interval [CI], 2.16 to 2.84), having a clinical T1 tumor (OR, 2.51; 95% CI, 2.27 to 2.78), and having a tumor without an extensive intraductal component (OR, 2.07; 95% CI, 1.81 to 2.37) were the strongest predictors of breast-conserving surgery. Radiation therapy was given to 86% of patients who had breast-conserving surgery. Age less than 70 years was the most significant predictor of receiving radiation (OR, 2.11; 95% CI, 1.77 to 2.25). Tumor variables did not correlate with the use of radiation, but favorable tumor characteristics were associated with the use of breast-conserving surgery.

CONCLUSION: Despite strong evidence supporting the use of BCT, the majority of women continue to be treated with mastectomy. Predictors of the use of BCT do not correspond to those suggested in guidelines.
Phase I Trial of 72-Hour Continuous Infusion UCN-01 in Patients With Refractory Neoplasms
Authors: Sausville Edward A. , Arbuck Susan G. , Messmann Richard , Headlee Donna , Bauer Kenneth S. , Lush Richard M. , Murgo Anthony , Figg William D. , Lahusen Tyler , Jaken Susan , Jing Xiu-xian , Roberge Michel , Fuse Eiichi , Kuwabara Takashi , Senderowicz Adrian M.
Published: February 2017

PURPOSE: To define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of the novel protein kinase inhibitor, UCN-01 (7-hydroxystaurosporine), administered as a 72-hour continuous intravenous infusion (CIV).

PATIENTS AND METHODS: Forty-seven patients with refractory neoplasms received UCN-01 during this phase I trial. Total, free plasma, and salivary concentrations were determined; the latter were used to address the influence of plasma protein binding on peripheral tissue distribution. The phosphorylation state of the protein kinase C (PKC) substrate alpha-adducin and the abrogation of DNA damage checkpoint also were assessed.

RESULTS: The recommended phase II dose of UCN-01 as a 72-hour CIV is 42.5 mg/m2/d for 3 days. Avid plasma protein binding of UCN-01, as measured during the trial, dictated a change in dose escalation and administration schedules. Therefore, nine patients received drug on the initial 2-week schedule, and 38 received drug on the recommended 4-week schedule. DLTs at 53 mg/m2/d for 3 days included hyperglycemia with resultant metabolic acidosis, pulmonary dysfunction, nausea, vomiting, and hypotension. Pharmacokinetic determinations at the recommended dose of 42.5 mg/m2/d for 3 days included mean total plasma concentration of 36.4 μM (terminal elimination half-life range, 447 to 1176 hours), steady-state volume of distribution of 9.3 to 14.2 L, and clearances of 0.005 to 0.033 L/h. The mean total salivary concentration was 111 nmol/L of UCN-01. One partial response was observed in a patient with melanoma, and one protracted period ( > 2.5 years) of disease stability was observed in a patient with alk-positive anaplastic large-cell lymphoma. Preliminary evidence suggests UCN-01 modulation of both PKC substrate phosphorylation and the DNA damage-related G2 checkpoint.

CONCLUSION: UCN-01 can be administered safely as an initial 72-hour CIV with subsequent monthly doses administered as 36-hour infusions.
Hormone Replacement Therapy After Breast Cancer: A Systematic Review and Quantitative Assessment of Risk
Authors: Col Nananda F. , Hirota Linda K. , Orr Richard K. , Erban John K. , Wong John B. , Lau Joseph
Published: February 2017

PURPOSE: Hormone replacement therapy (HRT) is typically withheld from women with breast cancer because of concern that it might increase the risk of recurrence. The purpose of this study was to quantify the risk of recurrent breast cancer associated with HRT among breast cancer survivors.

METHODS: We performed a systematic literature review through May 1999, calculating the relative risk (RR) of breast cancer recurrence in each study by comparing the number of recurrences in the HRT group to those in the control group. In studies that did not contain a control group, we constructed one by estimating the expected number of recurrences based on data from the Early Breast Cancer Trialists’ Collaborative Group, adjusting for nodal status and disease-free interval. RRs across all studies were combined using random-effects models.

RESULTS: Of the 11 eligible studies, four had control groups and included 214 breast cancer survivors who began HRT after a mean disease-free interval of 52 months. Over a mean follow-up of 30 months, 17 of 214 HRT users experienced recurrence (4.2% per year), compared with 66 of 623 controls (5.4% per year). HRT did not seem to affect breast cancer recurrence risk (RR = 0.64, 95% confidence interval [CI], 0.36 to 1.15). Including all 11 studies in the analyses (669 HRT users), using estimated control groups for the seven uncontrolled trials, the combined RR was 0.82 (95% CI, 0.58 to 1.15).

CONCLUSION: Although our analyses suggest that HRT has no significant effect on breast cancer recurrence, these findings were based on observational data subject to a variety of biases.
Changes in Weight, Body Composition, and Factors Influencing Energy Balance Among Premenopausal Breast Cancer Patients Receiving Adjuvant Chemotherapy
Authors: Demark-Wahnefried Wendy , Peterson Bercedis L. , Winer Eric P. , Marks Lawrence , Aziz Noreen , Marcom P. Kelly , Blackwell Kimberly , Rimer Barbara K.
Published: February 2017

PURPOSE: Weight gain is a common problem among breast cancer patients who receive adjuvant chemotherapy (CT). We undertook a study to determine the causes of this energy imbalance.

PATIENTS AND METHODS: Factors related to energy balance were assessed at baseline (within 3 weeks of diagnosis) and throughout 1 year postdiagnosis among 53 premenopausal women with operable breast carcinoma. Thirty-six patients received CT and 17 received only localized treatment (LT). Measures included body composition (dual energy x-ray absorptiometry), resting energy expenditure (REE; indirect calorimetry), dietary intake (2-day dietary recalls and food frequency questionnaires) and physical activity (physical activity records).

RESULTS: Mean weight gain in the LT patients was 1.0 kg versus 2.1 kg in the CT group (P = .02). No significant differences between groups in trend over time were observed for REE and energy intake; however, a significant difference was noted for physical activity (P = .01). Several differences between groups in 1-year change scores were detected. The mean change (± SE) in LT versus CT groups and P values for uncontrolled/controlled (age, race, radiation therapy, baseline body mass index, and end point under consideration) analysis are as follows: percentage of body fat (−0.1 ± 0.4 v +2.2 ± 0.6%; P = .001/0.04); fat mass (+0.1 ± 0.3 v +2.3 ± 0.7 kg; P = .002/0.04); lean body mass (+0.8 ± 0.2 v −0.4 ± 0.3 kg; P = .02/0.30); and leg lean mass (+0.5 ± 0.1 v −0.2 ± 0.1 kg; P = .01/0.11).

CONCLUSION: These data do not support overeating as a cause of weight gain among breast cancer patients who receive CT. The data suggest, however, that CT-induced weight gain is distinctive and indicative of sarcopenic obesity (weight gain in the presence of lean tissue loss or absence of lean tissue gain). The development of sarcopenic obesity with evidence of reduced physical activity supports the need for interventions focused on exercise, especially resistance training in the lower body, to prevent weight gain.
Differential Expression of Metastasis-Associated Genes in Papilla of Vater and Pancreatic Cancer Correlates With Disease Stage
Authors: Friess Helmut , Guo Xiao-Zhong , Tempia-Caliera Adrien A. , Fukuda Akira , Martignoni Marcus E. , Zimmermann Arthur , Korc Murray , Büchler Markus W.
Published: February 2017

PURPOSE: Papilla of Vater cancer has a much better prognosis than pancreatic cancer. It is not known whether this is the result of differences in the tumor biology of the two malignancies. Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic cancer.

PATIENTS AND METHODS: Analysis was performed in nine normal human papilla of Vater samples, 27 papilla of Vater cancers, 16 normal pancreatic samples, and 29 pancreatic cancers. Expression of nm23-H1 and KAI1 was analyzed by Northern blot analysis and in situ hybridization. In addition, immunohistochemistry was performed to localize the respective proteins.

RESULTS: There was no difference in nm23-H1 and KAI1 mRNA expression levels in normal versus cancerous papilla of Vater samples. In contrast, nm23-H1 and KAI1 RNA expression was upregulated in early tumor stages of pancreatic cancer and reduced in advanced tumor stages. When expression of nm23-H1 and KAI1 RNA was analyzed by use of in situ hybridization, normal epithelial cells of the papilla of Vater exhibited mRNA staining intensity similar to that of papilla of Vater cancer cells. Similar levels of nm23-H1 and KAI1 immunoreactivity also were observed in these samples. In contrast, early stage pancreatic cancer samples exhibited stronger nm23-H1 and KAI1 immunoreactivity than normal controls. Furthermore, early pancreatic cancer stages exhibited higher KAI1 and nm23-H1 immunostaining than advanced tumor stages.

CONCLUSION: Differences in the expression patterns of the two tumor suppressor genes nm23-H1 and KAI1 may contribute to the different prognoses of papilla of Vater cancer and pancreatic cancer. Our findings support the hypothesis that biologic differences rather than earlier diagnosis influence the different outcomes of these two tumor entities.
Determinants of the Use of Complementary Therapies by Patients With Cancer
Authors: Paltiel O. , Avitzour M. , Peretz T. , Cherny N. , Kaduri L. , Pfeffer R. M. , Wagner N. , Soskolne V.
Published: February 2017

PURPOSE: We performed a survey of Israeli oncology patients to examine the extent of their use of complementary therapies (CT) and to compare sociodemographic, psychologic, and medical characteristics, attitudes, and quality of life of users and nonusers of CT.

PATIENTS AND METHODS: Questionnaires were administered to 1,027 patients attending ambulatory and inpatient hematology or oncology facilities at three hospitals. Medical information was extracted from charts. Univariate and multivariate comparisons of users and nonusers of CT were performed.

RESULTS: A total of 526 participants (51.2%) had used CT since their diagnosis, and 357 patients (34.9%) had used CT recently (in the past 3 months). Factors that multivariate analysis found to be significantly associated (P < .05) with recent CT use were as follows: female sex; age 35 to 59 years; more education; coming to the hospital by private car; advanced disease status; having a close friend or a relative with cancer; and attending support groups or individual counseling. After controlling for these factors, individually examined psychosocial variables associated with recent CT use included the following (odds ratios [OR] with 95% confidence intervals [CI]): needs unmet by conventional medicine (OR, 2.76; 95% CI, 1.95 to 3.89); helplessness (OR, 1.39; 95% CI, 1.0 to 1.91); incomplete trust in the doctor (OR, 1.49; 95% CI, 1.08 to 2.06); and changed outlook or beliefs since the diagnosis of cancer (OR, 1.47; 95% CI, 1.07 to 2.02). Functional quality of life (including physical, emotional, social, and role function) and symptom (fatigue and diarrhea) scores were significantly worse for recent CT users compared with nonusers, controlling for age, sex, and current disease status.

CONCLUSION: Characteristics associated with CT use include age, sex, education, and advanced disease. Significant associations between CT use and attending supportive psychotherapy, unmet needs, helplessness, and worse emotional and social function indicate considerable distress, suggesting that increased attention to psychosocial needs within oncologic settings is warranted.
Combination Paclitaxel, Carboplatin, and Gemcitabine Is an Active Treatment for Advanced Urothelial Cancer
Authors: Hussain Maha , Vaishampayan Ulka , Du Wei , Redman Bruce , Smith David C.
Published: February 2017

PURPOSE: To determine the efficacy and toxicity of the drug combination of carboplatin, paclitaxel, and gemcitabine in patients with advanced urothelial carcinoma.

PATIENTS AND METHODS: Patients eligible included those with advanced urothelial malignancy of any histology, no previous chemotherapy for metastatic disease, Southwest Oncology Group performance status of 2 or less, serum creatinine levels of 2 mg/dL or less, and adequate bone marrow and hepatic function. Treatment consisted of paclitaxel 200 mg/m2, carboplatin (target area under the curve = 5) on day 1, and gemcitabine 800 mg/m2 on days 1 and 8, repeated every 21 days.

RESULTS: Forty-nine patients (44 men and five women) were enrolled; the patients’ median age was 63 years, and their median creatinine clearance was 78 mL/min (range, 26 to 165 mL/min). Forty-three patients had transitional cell carcinoma, and six had squamous cell carcinoma or mixed histology. Ten patients had metastases to lymph nodes only, six had locally advanced disease, four had locally recurrent disease, 24 patients had visceral metastases, and five had soft tissue metastases. Twenty-one patients had disease in one site, 16 in two sites, and 12 in three sites. A total of 272 cycles were administered (median, six cycles; range, 1 to 15 cycles). Major toxicities were grade 3 and 4 neutropenia in 17 and 19 patients, respectively; grade 3 and 4 thrombocytopenia in 15 and six patients, respectively; grade 3 and 4 anemia in 10 and two patients, respectively; grade 3 neuropathy in four patients; and diarrhea in two patients. The incidence of febrile neutropenia was 1.4%; no patients died of drug toxicity. Forty-seven of the 49 patients were assessable for response. Fifteen (32%) patients experienced a complete response, and 17 (36%) patients experienced a partial response (32 of 47 patients, 68%; 95% confidence interval, 56.27 to 82.86). Responses were seen in all sites, including 15 (68%) of 22 patients with visceral metastases. The median survival was 14.7 months, with a 1-year survival of 59%.

CONCLUSION: Combination paclitaxel, carboplatin, and gemcitabine is active; an encouraging number of patients with advanced urothelial carcinoma treated with this regimen experienced complete remission.
Predicting Outcome to Chemotherapy in Patients With Germ Cell Tumors: The Value of the Rate of Decline of Human Chorionic Gonadotrophin and Alpha-Fetoprotein During Therapy
Authors: Mazumdar M. , Bajorin D.F. , Bacik J. , Higgins G. , Motzer R.J. , Bosl G.J.
Published: February 2017

PURPOSE: The prognostic significance of the rate of decline of the serum tumor marker alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) during the first two cycles of chemotherapy in germ cell tumor (GCT) patients was initially reported by us, but its value has been debated. We re-examined this issue in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification system and investigated the role of including in the analysis patients whose markers normalized early.

PATIENTS AND METHODS: One hundred eighty-nine GCT patients with elevated AFP/HCG marker values treated with platinum-based chemotherapy between 1986 and 1998 were included in this analysis. Patients were classified as good, intermediate, or poor risk by the IGCCCG criteria and as having satisfactory or unsatisfactory marker decline. Risk and marker decline were correlated with response, event-free survival, and overall survival.

RESULTS: Satisfactory marker decline predicted improved complete response (CR) proportion and event-free and overall survival (P < .0001). The CR proportion, 2-year event-free, and 2-year overall survival rates for patients with a satisfactory and unsatisfactory marker decline were 92% versus 62%, 91% versus 69%, and 95% versus 72%, respectively. Marker decline remained a significant variable for all three end points when adjusted for risk (P < .01) with the outcome differences most pronounced in the poor-risk group.

CONCLUSION: The rate of marker decline during chemotherapy has prognostic value independent of risk and may play a significant role in the management of poor-risk patients. It is appropriate to include patients whose markers normalized early.
An Online Educational Facility for Medical Oncology Trainees: www.vmotg.org
Authors: Jefford Michael , Phillips Kelly-Anne , Tattersall Martin H.N.
Published: February 2017

PURPOSE: To design, implement, and evaluate a comprehensive educational Web site for medical oncology trainees.

METHODS: The Web site was designed with three main areas (termed Journal Club, Key Papers, and Oncology Links) and compiled from articles presented at the Victorian Medical Oncology Trainees’ Group journal club from the preceding 3 years. The Key Papers section was then reviewed by 30 academic medical oncologists. The site was advertised by mail and at the Annual Meeting of the Medical Oncology Group of Australia. Evaluation was by mail survey.

RESULTS: The Web site, which may be accessed at www.vmotg.org, comprises more than 170 pages and 30,000 words of text. Journal club sessions are summarized with presented articles linked to abstracts from PubMed. Key Papers lists from five to 25 pivotal articles in each of 35 categories. Oncology Links is an extensive list of links in 10 categories including organizations, journals, and practice guidelines. Twenty-six of 45 trainees and 82 of 190 oncologists responded to the survey. Eighty-one percent of these trainees and 28% of oncologists have used the Web site. Ninety-six percent consider the Web site easy to use and “a useful medical oncology resource.” All trainees rated the site good to excellent in terms of relevance and 94% considered the site beneficial to their education.

CONCLUSION: The Web site www.vmotg.org is a relevant and useful educational resource for Australian medical oncology trainees and oncologists. As far as the authors are aware, this is the only educational site specifically for medical oncology trainees throughout the world. It may be a valuable oncology education resource for trainees in other countries, particularly those in isolated areas.
Enhanced Humoral Immune Response Correlates With Improved Disease-Free and Overall Survival in American Joint Committee on Cancer Stage II Melanoma Patients Receiving Adjuvant Polyvalent Vaccine
Authors: DiFronzo L. Andrew , Gupta Rishab K. , Essner Richard , Foshag Leland J. , O’Day Steven J. , Wanek Leslie A. , Stern Stacey L. , Morton Donald L.
Published: February 2017

PURPOSE: Although the improved overall survival (OS) of patients who receive Canvaxin (CancerVax Corp, Carlsbad, CA) polyvalent vaccine (PV) immunotherapy for metastatic melanoma has been correlated with cellular and humoral immune responses, the mechanisms of vaccine immunotherapy for early-stage melanoma are unclear. Specific immune responses to tumor-associated antigens might correlate with disease-free survival (DFS) and OS in patients receiving adjuvant PV therapy for primary melanoma.

PATIENTS AND METHODS: Eighty-three patients received PV plus bacille Calmette-Guérin after wide excision of American Joint Committee on Cancer stage II melanoma. Humoral and cellular responses during the first 12 weeks of adjuvant immunotherapy were assessed by serum antibody titers to a tumor-associated 90-kd glycoprotein antigen (TA90) expressed by PV, and by delayed-type hypersensitivity (DTH) skin testing with PV (PV-DTH).

RESULTS: At a median follow-up period of 46.6 months (range, 10.7 to 93.6 months), an increased PV-DTH response seemed to be associated with improved 5-year DFS (54% v 20%) and 5-year OS (75% v 60%), but the correlations were not statistically significant. Anti-TA90 immunoglobulin (Ig) M levels ≥ 1:800 were significantly correlated with improved 5-year DFS and improved 5-year OS, and multivariate analysis identified anti-TA90 IgM as an independent prognostic factor for OS and DFS.

CONCLUSION: These findings suggest that an increased IgM response in patients receiving PV therapy for stage II melanoma is associated with decreased recurrence and improved survival.
Predictors of Local-Regional Recurrence After Neoadjuvant Chemotherapy and Mastectomy Without Radiation
Authors: Buchholz Thomas A. , Tucker Susan L. , Masullo Lawrence , Kuerer Henry M. , Erwin Jessica , Salas Jessica , Frye Debbie , Strom Eric A. , McNeese Marsha D. , Perkins George , Katz Angela , Singletary S. Eva , Hunt Kelly K. , Buzdar Aman U. , Hortobagyi Gabriel N.
Published: February 2017

PURPOSE: To define clinical and pathologic predictors of local-regional recurrence (LRR) for patients treated with neoadjuvant chemotherapy and mastectomy without radiation.

PATIENTS AND METHODS: We analyzed the outcome of the 150 breast cancer cases treated on prospective institutional trials with neoadjuvant chemotherapy and mastectomy without postmastectomy radiation. Clinical stage at diagnosis was I in 1%, II in 43%, IIIA in 23%, IIIB in 25%, and IV in 7%. No patient had inflammatory breast cancer.

RESULTS: The median follow-up period of surviving patients was 4.1 years. The 5- and 10-year actuarial rates of LRR were both 27%. Pretreatment factors that positively correlated with LRR were increasing T stage (P < .0001) and increasing combined clinical stage (P < .0001). Pathologic and treatment factors that positively correlated with LRR were size of the residual primary tumor (P = .0048), increasing number of involved lymph nodes (P < .0001), and no use of tamoxifen (P = .0013). The LRR rate for the 18 patients with a pathologic complete response of both the primary tumor and lymph nodes (pCR) was 19% (95% confidence interval, 6% to 48%). In a forward stepwise Cox logistic regression analysis, clinical stage IIIB or greater (hazard ratio of 4.5, P < .001), pathologic involvement of four or more lymph nodes (hazard ratio of 2.7, P = .008), and no use of tamoxifen (hazard ratio of 3.9, P = .027) independently predicted for LRR.

CONCLUSION: Advanced disease at presentation and positive lymph nodes after chemotherapy predict for clinically significant rates of LRR. Achievement of pCR does not preclude the need for postmastectomy radiation if warranted by the pretreatment stage of the disease.
High-Dose Samarium-153 Ethylene Diamine Tetramethylene Phosphonate: Low Toxicity of Skeletal Irradiation in Patients With Osteosarcoma and Bone Metastases
Authors: Anderson Peter M. , Wiseman Gregory A. , Dispenzieri Angela , Arndt Carola A.S. , Hartmann Lynn C. , Smithson William A. , Mullan Brian P. , Bruland Oyvind S.
Published: February 2017

PURPOSE: Samarium-153 ethylene diamine tetramethylene phosphonate (153Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic bone metastases. Because the dose-limiting toxicity of 153Sm-EDTMP is thrombocytopenia, a dose-escalation trial using peripheral-blood progenitor cells (PBPCs) or marrow support was conducted to treat metastatic bone cancer.

PATIENTS AND METHODS: Patients with locally recurrent or metastatic osteosarcoma or skeletal metastases avid on bone scan were treated with 1, 3, 4.5, 6, 12, 19, or 30 mCi/kg of 153Sm-EDTMP.

RESULTS: Thirty patients were treated with 153Sm-EDTMP. Transient symptoms of hypocalcemia were seen at 30 mCi/kg. Estimates of radioisotope bound to bone surfaces and marrow radiation dose were linear with injected amount of 153Sm-EDTMP. Cytopenias also occurred in all subjects and were dose-related. At day +13 after 153Sm-EDTMP, residual whole-body radioactivity was 1% to 65% of whole-body radioactivity considered safe for PBPC infusion, 3.6 mCi. After PBPC or marrow infusion on day +14 after 153Sm-EDTMP, recovery of hematopoiesis was problematic in two patients at the 30 mCi/kg dose infused with less than 2 × 106 CD34+/kg on day +14, but not in other patients. Reduction or elimination of opiates for pain was seen in all patients. Patients had no adverse changes in appetite or performance status.

CONCLUSION: 153Sm-EDTMP with PBPC support can provide bone-specific therapeutic irradiation (estimates of 39 to 241 Gy). Hematologic toxicity at 30 mCi 153Sm-EDTMP/kg requires PBPC grafts with more than 2 × 106 CD34+/kg to overcome myeloablative effects of skeletal irradiation. Nonhematologic side effects are minimal.
Follow-Up of Complete Cytogenetic Remission in Patients With Chronic Myeloid Leukemia After Cessation of Interferon Alfa
Authors: Mahon F. X. , Delbrel X. , Cony-Makhoul P. , Fabères C. , Boiron J. M. , Barthe C. , Bilhou-Nabéra C. , Pigneux A. , Marit G. , Reiffers J.
Published: February 2017

PURPOSE: A small proportion of patients with chronic myeloid leukemia (CML) achieve a complete cytogenetic response (CCR), defined as the disappearance of Philadelphia (Ph) chromosome–positive metaphases, after treatment with interferon alfa (IFN). In this population of patients, the question of whether treatment should then be withdrawn is not yet resolved.

PATIENTS AND METHODS: In the present study, we followed 15 patients who stopped IFN after achieving CCR. In nine patients IFN was stopped in view of adverse reactions (n = 8) or patient’s choice (n = 1). For the remaining six patients, the treatment was stopped because no BCR/ABL rearrangement could be detected by reverse transcriptase polymerase chain reaction (RT-PCR) in four successive analyses using peripheral-blood samples.

RESULTS: Loss of CCR and survival were not statistically different (P = .48; P = .7) for the 15 patients who stopped IFN compared with 41 other CCR patients who continued IFN therapy in our institution. The median follow-up after discontinuation of IFN treatment was 36 months (range, 6 to 108 months). Seven patients (47%) (females, or CCR > 24 months and RT-PCR negative before IFN cessation; P < .0001) did not relapse. Eight other patients (53%) relapsed (lost CCR) within 3 to 33 months of treatment discontinuation. One of them relapsed in major cytogenetic remission (MCR) and was still in MCR 87 months after stopping therapy without any treatment.

CONCLUSION: It is possible to stop IFN treatment at least in some patients with CML who achieve a prolonged period of CCR. This study also illustrates the hypothesis that persistence of low numbers of Ph-positive cells does not necessarily imply hematologic relapse.
Treatment of Childhood Acute Lymphoblastic Leukemia: Results of Dana-Farber ALL Consortium Protocol 87-01
Authors: LeClerc Jean Marie , Billett Amy L. , Gelber Richard D. , Dalton Virginia , Tarbell Nancy , Lipton Jeffrey M. , Barr Ronald , Clavell Luis A. , Asselin Barbara , Hurwitz Craig , Schorin Marshall , Lipshultz Steven E. , Declerck Lieven , Silverman Lewis B. , Cohen Harvey J. , Sallan Stephen E.
Published: February 2017

PURPOSE: To improve efficacy and reduce toxic- ity of treatment for children with acute lymphoblas- tic leukemia.

PATIENTS AND METHODS: Patients from all risk groups, including infants and those with T-cell disease, were treated between 1987 and 1991. Standard-risk (SR) patients did not receive cranial irradiation, whereas high-risk (HR) and very high-risk (VHR) patients participated in a randomized comparison of 18 Gy of cranial irradiation conventionally fractionated versus two fractions per day (hyperfractionated).

RESULTS: At a median follow-up of 9.2 years, the 9-year event-free survival (EFS ± SE) was 75% ± 2% for all 369 patients, 77% ± 4% for the 142 SR patients, and 73% ± 3% for the 227 HR/VHR patients (P = .37 comparing SR and HR/VHR). The CNS, with or without concomitant bone marrow involvement, was the first site of relapse in 19 (13%) of the 142 SR patients: 16 (20%) of 79 SR boys and three (5%) of 63 SR girls. This high incidence of relapses necessitated a recall of SR boys for additional therapy. CNS relapse occurred in only two (1%) of 227 HR and VHR patients. There were no outcome differences found among randomized treatment groups. Nine-year overall survival was 84% ± 2% for the entire population, 93% ± 2% for SR children, and 79% ± 3% for HR and VHR children (P < .01 comparing SR and HR/VHR).

CONCLUSION: A high overall survival outcome was obtained for SR patients despite the high risk of CNS relapse for SR boys, which was presumed to be associated with eliminating cranial radiation without intensifying systemic or intrathecal chemotherapy. For HR/VHR patients, inability to salvage after relapse (nearly all of which were in the bone marrow) remains a significant clinical problem.
Costs of Treatment for Elderly Women With Early-Stage Breast Cancer in Fee-for-Service Settings
Authors: Warren Joan L. , Brown Martin L. , Fay Michael P. , Schussler Nicola , Potosky Arnold L. , Riley Gerald F.
Published: February 2017

PURPOSE: This study provides population-based estimates of the treatment costs for elderly women with early-stage breast cancer, with emphasis on costs of modified radical mastectomy (MRM) compared with breast-conserving surgery (BCS) and radiation therapy (RT).

PATIENTS AND METHODS: Women with breast cancer from the Surveillance, Epidemiology, and End Results cancer registries were linked with their Medicare claims, 1990 through 1998. Each claim was assigned to an initial, continuing, or terminal care phase after a cancer diagnosis. Mean monthly phase-specific costs were determined for all health care and for treatment related only to cancer. Cumulative long-term costs of care that accrue during a women’s remaining lifetime were calculated by treatment group.

RESULTS: Initial care costs for the 6 months after diagnosis for women who underwent BCS with RT were approximately $450 per month higher than for women with MRM. During the continuing-care phase, costs for women undergoing BCS with RT were significantly less expensive than for MRM cases. The two groups had similar costs in the terminal-care phase. Assuming the same survival distributions, long-term costs for women undergoing BCS with RT were not statistically different than for women undergoing MRM.

CONCLUSION: Although mastectomy was less costly in the initial phase, the lifetime costs of BCS with RT and mastectomy were equivalent. Thus, women’s preferences, resources to cover out-of-pocket costs, and life situations should be the major factors addressed in shared decision making about treatment options.
Fasting Insulin and Outcome in Early-Stage Breast Cancer: Results of a Prospective Cohort Study
Authors: Goodwin Pamela J. , Ennis Marguerite , Pritchard Kathleen I. , Trudeau Maureen E. , Koo Jarley , Madarnas Yolanda , Hartwick Warren , Hoffman Barry , Hood Nicky
Published: February 2017

PURPOSE: Insulin, a member of a family of growth factors that includes insulin-like growth factor (IGF)-I and IGF-II, exerts mitogenic effects on normal and malignant breast epithelial cells, acting via insulin and IGF-I receptors. Because of this and because of its recognized association with obesity, an adverse prognostic factor in breast cancer, we examined the prognostic associations of insulin in early-stage breast cancer.

PATIENTS AND METHODS: A cohort of 512 women without known diabetes, who had early-stage (T1 to T3, N0 to N1, and M0) breast cancer, was assembled and observed prospectively. Information on traditional prognostic factors and body size was collected, and fasting blood was obtained.

RESULTS: Fasting insulin was associated with distant recurrence and death; the hazard ratios and 95% confidence intervals (CI) for those in the highest (> 51.9 pmol/L) versus the lowest (< 27.0 pmol/L) insulin quartile were 2.0 (95% CI, 1.2 to 3.3) and 3.1 (95% CI, 1.7 to 5.7), respectively. There was some evidence to suggest that the association of insulin with breast cancer outcomes may be nonlinear. Insulin was correlated with body mass index (Spearman r = 0.59, P < .001), which, in turn, was associated with distant recurrence and death (P < .001). In multivariate analyses that included fasting insulin and available tumor- and treatment-related variables, adjusted hazard ratios for the upper versus lower insulin quartile were 2.1 (95% CI, 1.2 to 3.6) and 3.3 (95% CI, 1.5 to 7.0) for distant recurrence and death, respectively.

CONCLUSION: Fasting insulin level is associated with outcome in women with early breast cancer. High levels of fasting insulin identify women with poor outcomes in whom more effective treatment strategies should be explored.
Biologic Correlates of 18Fluorodeoxyglucose Uptake in Human Breast Cancer Measured by Positron Emission Tomography
Authors: Bos Reinhard , van der Hoeven Jacobus J.M. , van der Wall Elsken , van der Groep Petra , van Diest Paul J. , Comans Emile F.I. , Joshi Urvi , Semenza Gregg L. , Hoekstra Otto S. , Lammertsma Adriaan A. , Molthoff Carla F.M.
Published: February 2017

PURPOSE: Variable uptake of the glucose analog 18fluorodeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especially in lobular cancer. At present, no satisfactory biologic explanation exists for this phenomenon. This study compared 18FDG uptake in vivo with biomarkers expected to be involved in the underlying biologic mechanisms.

PATIENTS AND METHODS: Preoperative 18FDG-PET scans were performed in 55 patients. 18FDG activity was assessed visually by three observers using a four-point score. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut-1); Hexokinase (HK) I, II, and III; macrophages; hypoxia-inducible factor-1-alfa (HIF-1α); vascular endothelial growth factor (VEGF165); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed.

RESULTS: There were positive correlations between 18FDG uptake and Glut-1 expression (P < .001), MAI (P = .001), amount of necrosis (P = .010), number of tumor cells/volume (P = .009), expression of HK I (P = .019), number of lymphocytes (P = .032), and microvessel density (r = .373; P = .005). HIF-1α, VEGF165, HK II, HK III, and macrophages showed no univariate correlation with 18FDG. In logistic regression, however, HIF-1α and HK II added value to MAI and Glut-1.

CONCLUSION: 18FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of 18FDG into the cell, HK for entering 18FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis), number of lymphocytes (not macrophages), and HIF-1α for upregulating Glut-1. Together, these features explain why breast cancers vary in 18FDG uptake and elucidate the low uptake in lobular breast cancer.
Accuracy of Recorded Tumor, Node, and Metastasis Stage in a Comprehensive Cancer Center
Authors: Brierley James D. , Catton Pamela A. , O’Sullivan Brian , Dancey Janet E. , Dowling Anthony J. , Irish Jonathan C. , McGowan Thomas S. , Sturgeon Jeremy F.G. , Swallow Carol J. , Rodrigues George B. , Panzarella Tony
Published: February 2017

PURPOSE: The benefits of recording the tumor, node, and metastasis (TNM) stages of cancer patients are well accepted, but little is known about how accurately this is performed. An audit was performed to determine the accuracy of recorded stage and to act as a baseline before the implementation of an education program.

PATIENTS AND METHODS: All new patient referrals to Princess Margaret Hospital between July 1 and August 31, 1997, were reviewed. An audit panel composed of five health record technicians (HRTs) and 10 doctors was assembled. Each auditor reviewed 10% of the health record. If there was a discrepancy between the stage in the health record and the auditor stage, then the final stage was determined by the audit committee. Analysis of the agreement between the health record, the physician auditor, the HRT auditor, and the final stage was performed.

RESULTS: A total of 855 patients were referred with a new diagnosis of a malignancy for which there was a TNM stage system; 833 patients (97.4%) had a stage assigned. There was agreement between the health record stage and final stage in 80% (95% confidence interval [CI], 77% to 82%) of cases for clinical stage, compared with 90% (95% CI, 87% to 92%) for pathologic stage. Of the major site groups, lung was the least accurately recorded. The most common major discrepancies were due to the recording of X when a definite category could be assigned.

CONCLUSION: This audit demonstrates the importance of staging and provides impetus to develop staging guidelines and education programs.
Paratesticular Rhabdomyosarcoma: Report From the Italian and German Cooperative Group
Authors: Ferrari A. , Bisogno G. , Casanova M. , Meazza C. , Piva L. , Cecchetto G. , Zanetti I. , Pilz T. , Mattke A. , Treuner J. , Carli M.
Published: February 2017

PURPOSE: We report the experience of the German-Italian Cooperative Group with 216 pediatric patients with paratesticular rhabdomyosarcoma treated over 20 years.

PATIENTS AND METHODS: At diagnosis, 198 patients had localized disease and 18 had distant metastases. Among the nonmetastatic patients, complete tumor resection was performed in 83% of cases. Evaluation of the retroperitoneal lymph nodes changed over the years from routine surgical staging to radiologic assessment. All patients received chemotherapy, which was reduced in intensity and duration for patients with low-risk features in subsequent protocols. Radiotherapy was administered to 10% of patients.

RESULTS: Among 72 patients with a negative retroperitoneal computed tomography (CT) scan, surgical assessment detected nodal involvement in only one case. Among 23 patients with enlarged nodes on CT scans, surgery confirmed nodal spread in 65% of patients. No differences in the rate of nodal involvement were observed over the years. With a median follow-up of 110 months, 5-year survival was 85.5% for the series as a whole, 94.6% for patients with localized disease, and 22.2% for metastatic cases. Retroperitoneal nodal recurrence was the major cause of treatment failure. Univariate analysis revealed the prognostic value of tumor invasiveness, size, and resectability, as well as of nodal involvement and age, in patients with localized tumor.

CONCLUSION: The outcome for patients with localized paratesticular rhabdomyosarcoma is excellent, despite the reduction in chemotherapy over the years: an alkylating agent–free and anthracycline-free regimen is adequate treatment for low-risk patients. Surgical assessment of the retroperitoneum must be reserved for patients with enlarged nodes on CT scans. Children over 10 years old carry a higher risk of nodal involvement and relapse.
Gross Genomic Aberrations in Precancers: Clinical Implications of a Long-Term Follow-Up Study in Oral Erythroplakias
Authors: Sudbø Jon , Kildal Wanja , Johannessen Anne C. , Koppang Hanna S. , Sudbø Asle , Danielsen Håvard E. , Risberg Björn , Reith Albrecht
Published: February 2017

PURPOSE: Gross genomic aberrations are increasingly seen as a cause rather than a consequence of carcinogenesis. Carcinomas may be prevented by systemically acting agents when used in high-risk individuals. If gross genomic aberrations could be shown to be predictive markers in precancers, they could serve as a tool for identifying high-risk individuals to be included in chemopreventive trials.

PATIENTS AND METHODS: To investigate the predictive power of gross genomic aberrations in several types of oral premalignancies, we analyzed 57 biopsies from oral erythroplakias of 37 patients, both histologically and for DNA content. DNA content was measured by high-resolution image cytometry, and distribution histograms of DNA content were generated and interpreted according to established protocols. The primary end point was cancer-free survival.

RESULTS: Fifty-seven dysplastic oral red lesions from 37 patients were investigated. Forty-one lesions from 25 patients were classified with aberrant DNA content (DNA aneuploidy), of which 23 patients (92%) later developed an oral carcinoma (after a median observation time of 53 months; range, 29 to 79 months). Of 12 patients having altogether 16 lesions with normal DNA content, none developed a carcinoma (median observation time, 98 months; range, 23 to 163 months; P < .001). In multivariate analysis, DNA content was a significant prognostic factor (P < .001), whereas histologic grade, sex, use of tobacco, size and location of lesions, and the presence multiple of lesions were not.

CONCLUSION: Gross genomic aberrations are highly predictive for the subsequent occurrence of carcinomas from a wide range of oral premalignancies.
Extraosseous Osteosarcoma: Response to Treatment and Long-Term Outcome
Authors: Ahmad Syed A. , Patel Shreyaskumar R. , Ballo Matthew T. , Baker Treneth P. , Yasko Alan W. , Wang Xuemei , Feig Barry W. , Hunt Kelly K. , Lin Patrick P. , Weber Kristen L. , Chen Lei L. , Zagars Gunar K. , Pollock Raphael E. , Benjamin Robert S. , Pisters Peter W.T.
Published: February 2017

PURPOSE: To evaluate the clinicopathologic features of extraosseous osteosarcoma (EOO), a rare soft tissue form of osteosarcoma, and to examine its response to multimodality therapy.

PATIENTS AND METHODS: The medical records of all patients with EOO evaluated at The University of Texas M.D. Anderson Cancer Center between 1960 and 1999 were reviewed for clinicopathologic factors, treatment, and outcome.

RESULTS: Sixty consecutive patients with EOO were identified, including 38 patients with localized (American Joint Committee on Cancer stages I to III) disease. The majority of patients presented with T2 tumors (n = 35, 58%), and 90% of tumors were located beneath the investing fascia. Twenty-seven patients with measurable and assessable disease were treated with doxorubicin-based chemotherapy (median doxorubicin starting dose, 75 mg/m2; median number of cycles, four). The overall response rate was 19%, with two complete and three partial responses; one (6%) of 18 doxorubicin-treated patients who underwent subsequent surgery had a pathologic complete response. For the subset of 30 patients with localized disease treated at M.D. Anderson, the 5-year actuarial local recurrence–free, distant recurrence–free, event-free, and disease-specific survival rates were 82% (95% confidence interval [CI], 70% to 98%), 64% (95% CI, 43% to 93%), 47% (95% CI, 30% to 70%), and 46% (95% CI, 26% to 80%), respectively.

CONCLUSION: EOO should be considered clinically and therapeutically distinct from osseous osteosarcoma. Radiographic response rates and pathologic complete response rates to doxorubicin-based systemic therapy are low.
Dose-Escalating Study of Capecitabine Plus Gemcitabine Combination Therapy in Patients With Advanced Cancer
Authors: Schilsky Richard L. , Bertucci Donna , Vogelzang Nicholas J. , Kindler Hedy L. , Ratain Mark J.
Published: February 2017

PURPOSE: The goals of this phase I study were to determine the maximum-tolerated doses of capecitabine and gemcitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT) and safety profile of this combination.

PATIENTS AND METHODS: Eligible patients had advanced solid tumors that had failed to respond to standard therapy or for which no standard therapy was available, measurable or assessable disease, Karnofsky performance status ≥ 70%, and acceptable organ function. Capecitabine was administered twice daily by mouth each day for 21 consecutive days followed by a 1-week break. Gemcitabine was administered as a 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break.

RESULTS: Forty patients were enrolled onto the study, and 33 are fully assessable for toxicity. The most common toxicities during the first cycle of chemotherapy were neutropenia and mucositis. Only one patient treated at gemcitabine and capecitabine doses of 800 and 2000 mg/m2, respectively, met protocol-specified DLT criteria; however, at these doses 65% of successive cycles required dose reduction or delay for toxicity. No episodes of DLT were observed at gemcitabine and capecitabine doses of 1,000 and 1,660 mg/m2, respectively, and 70% of cycles of therapy were delivered without dose reduction or delay. Therefore, these doses are recommended for further study. Tumor responses were observed in patients with metastatic colorectal and pancreatic cancer.

CONCLUSION: Gemcitabine and capecitabine can be combined with acceptable toxicity at nearly full doses. Antitumor activity of the combination merits further investigation in phase II studies.