bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor.
Authors: Estey E , Thall P , Andreeff M , Beran M , Kantarjian H , O'Brien S , Escudier S , Robertson L E , Koller C , Kornblau S
Published: February 2017

PURPOSE

To determine whether granulocyte colony-stimulating factor (G-CSF) administered before, during, and after fludarabine plus cytarabine (ara-C; FA) chemotherapy affected complete response (CR) rate, infection rate, blood count recovery, or survival in patients with newly diagnosed acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS).

PATIENTS AND METHODS

A total of 112 patients with newly diagnosed AML (n = 69) or MDS (n = 43) received G-CSF 400 micrograms/m2/d 1 day before (presenting WBC count < 50,000/microL) and/or during (all patients) fludarabine 30 mg/m2/d and ara-C 2 g/m2/d for 5 days (FLAG). G-CSF continued until a CR was achieved. Results were compared with those in 85 newly diagnosed patients (54 AML, 31 MDS) previously treated with FA without G-CSF.

RESULTS

Patients in both groups were relatively old (median age of all patients, 63 years), and were likely to have prognostically unfavorable cytogenetic abnormalities (36% had abnormalities of chromosomes 5 and 7 [-5/-7]). G-CSF accelerated recovery to > or = 1,000 neutrophils (P < .0001; median, 34 days for FA, 21 days for FLAG), but logistic regression provided no evidence that the CR rate was higher with FLAG than with FA (P = .50), with unadjusted CR rates of 63% and 53%, respectively. This may reflect relatively high rates of death before neutrophil recovery in both groups. Rates of infection were similar in both groups. The follow-up duration in remission is short, and much of these data remain censored. To date, survival is similar with FA and FLAG.

CONCLUSION

On average, G-CSF before, during, and after FA had no effect on CR or infection rates in this population, in which elderly patients and poor prognostic factors were prevalent. The use of FA and laminar airflow rooms rather than more usual therapy needs to be considered when analyzing the results.
Autologous and allogeneic bone marrow transplantation for chronic lymphocytic leukemia: preliminary results.
Authors: Khouri I F , Keating M J , Vriesendorp H M , Reading C L , Przepiorka D , Huh Y O , Andersson B S , van Besien K W , Mehra R C , Giralt S A
Published: February 2017

PURPOSE

This study was undertaken to evaluate the feasibility and therapeutic effect of high-dose chemoradiotherapy with autologous or allogeneic bone marrow transplantation (BMT) in patients with advanced chronic lymphocytic leukemia (CLL) who relapse after fludarabine treatment.

PATIENTS AND METHODS

Twenty-two patients with advanced CLL received high-dose cyclophosphamide, total-body irradiation, and BMT. Eleven patients with relapsed CLL received autologous BMT with marrow collected during a prior fludarabine-induced remission; leukemia cells were depleted from the autologous marrow in seven patients using an anti-CD19 monoclonal antibody and immunomagnetic separation. Eleven patients received allogeneic or syngeneic BMT, seven of whom had refractory Rai stage III or IV disease.

RESULTS

Six autologous transplant recipients achieved a complete remission (CR), four a nodular CR (nCR), and one a partial remission (PR). Two recurred with CLL, and three developed Richter's transformation. Two patients had recurrence of immune cytopenias while in morphologic remission; one of these patients died of cytomegalovirus pneumonia. Six of 11 patients survive in remission 2 to 29 months following BMT. Of the 11 patients who received allogeneic or syngeneic BMT, seven achieved a CR, two a nCR, and one a PR; 10 survive 2 to 36 months following BMT.

CONCLUSION

These data indicate that high-dose chemotherapy with allogeneic BMT is effective at producing CRs in patients with CLL. Autologous transplantation in CLL is feasible and is capable of producing remissions in patients with advanced CLL. Further studies are warranted to assess the role of BMT in the treatment of CLL.
Effects of topical tretinoin on dysplastic nevi.
Authors: Halpern A C , Schuchter L M , Elder D E , Guerry D , Elenitsas R , Trock B , Matozzo I
Published: February 2017

PURPOSE

As potential precursors of melanoma and markers of increased melanoma risk, dysplastic nevi are suitable targets of strategies for melanoma chemoprevention. We report the results of a pilot study of topical retinoic acid in patients with dysplastic nevi.

PATIENTS AND METHODS

Five male patients with dysplastic nevi applied tretinoin to half of the back for 6 months. Baseline photographs of dysplastic nevi were compared with posttreatment photographs and assessed for morphologic change. At study completion, each subject had four nevi excised from the treated side and four from the untreated side of the back. Biopsies were histologically evaluated for the presence of dysplasia.

RESULTS

All patients developed signs of irritation as a result of treatment. One patient was not compliant with treatment due to skin irritation. The four compliant patients showed significant decreases in the clinical atypia of treated lesions, with concomitant fading and even disappearance of many treated nevi. Histologically, only four of 16 treated nevi met histologic criteria for dysplasia, in comparison to 13 of 16 untreated nevi.

CONCLUSION

These results suggest that there is concomitant clinical and histologic improvement in a significant percentage of dysplastic nevi treated with topical tretinoin. However, the utility of topical tretinoin for chemoprevention of melanoma is limited by difficulty of application and associated inflammation. While new strategies in chemoprevention of melanoma are explored, sun protection and assiduous avoidance of sunburn must remain the mainstay of melanoma prevention.
11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia.
Authors: Pui C H , Behm F G , Downing J R , Hancock M L , Shurtleff S A , Ribeiro R C , Head D R , Mahmoud H H , Sandlund J T , Furman W L
Published: February 2017

PURPOSE

Leukemic cell characteristics were analyzed in infants less than 1 year of age with acute lymphoblastic leukemia (ALL) to determine adverse prognostic factors that might explain the poor prognosis of this group.

PATIENTS AND METHODS

Treatment outcomes were analyzed according to the presenting clinical and laboratory features of 30 infants treated between May 1979 and April 1993. A stepwise multivariate regression model was used to identify the most important prognostic indicator with respect to event-free survival.

RESULTS

Infant ALL cases were characterized by high presenting leukocyte count (median, 87 x 10(9)/L), increased frequency of CNS leukemia (50%), and blast cells with a CD10- phenotype (67%), myeloid-associated antigen expression (48%), and 11q23/MLL rearrangement (68%). The 11q23/MLL involvement was correlated with age less than 6 months, CD10- phenotype, myeloid-associated antigen expression, and high leukocyte count. Although 11q23/MLL involvement, age less than 6 months, myeloid-associated antigen expression, and female sex were each significantly associated with an inferior treatment outcome, only rearranged 11q23/MLL emerged as an independent predictor of prognosis in multivariate analysis (P = .01). Infants with this genetic abnormality had a 4.7-fold (95% confidence interval, 1.3- to 17.0-fold) increased risk in adverse events compared to other infants.

CONCLUSION

The 11q23/MLL involvement of blast cells identifies a major subgroup of infant ALL cases that require an innovative treatment approach. Infants who lack this genetic abnormality have an intermediate prognosis and could be treated accordingly on risk-directed protocols.
Intensive induction chemotherapy and radiation for organ preservation in patients with advanced resectable head and neck carcinoma.
Authors: Urba S G , Forastiere A A , Wolf G T , Esclamado R M , McLaughlin P W , Thornton A F
Published: February 2017

PURPOSE

We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the head and neck. The regimen consisted of intensive chemotherapy followed by radiation therapy alone for patients with good response to treatment. The end points of the study were response rate, organ preservation, toxicity, and survival.

PATIENTS AND METHODS

Forty-two eligible patients with carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, and paranasal sinuses were enrolled. Induction chemotherapy consisted of three cycles of mitoguazone, fluorouracil (5-FU), and high-dose continuous infusion cisplatin. Patients who had a complete response to chemotherapy, or whose tumor was downstaged to T1N1, were treated with definitive radiation therapy, to a total dose of 66 to 73.8 Gy. Patients with residual disease greater than T1N1 underwent surgery and postoperative radiation.

RESULTS

The overall response rate to chemotherapy was 84%, with a 43% complete response rate, and a 68% complete response rate at the primary tumor site. Sixty-nine percent of patients (29 of 42) were initially spared surgery to the primary tumor site, and four of these patients (14%) required neck dissection only, after radiation therapy. These tumor sites included oral cavity, oropharynx, hypopharynx, larynx, and sinuses. Eventually, five of these patients (17%) required salvage surgery and eight patients (28%) had unresectable or metastatic relapses. With a median follow-up duration of 38.5 months, 36% of all patients have had preservation of the primary tumor site and remain disease-free. The median survival duration is 26.8 months. Toxicity was substantial, with a 70% incidence of grade 3 to 4 granulocytopenia and two septic deaths.

CONCLUSION

Organ preservation without apparent compromise of survival was achieved in patients with selected nonlaryngeal sites of head and neck carcinoma. Larger site-specific trials with less toxic regimens conducted in randomized fashion are required to extend these data.
Evaluation and treatment of patients receiving radiation for cancer of the rectum or sigmoid colon in the United States: results of the 1988-1989 Patterns of Care Study process survey.
Authors: Coia L , Wizenberg M , Hanlon A , Gunderson L , Haller D , Hoffman J , Kline R , Mohiuddin M , Russell A , Tepper J
Published: February 2017

PURPOSE

For the first time, a Patterns of Care Study (PCS) was conducted in 1989 to determine the national practice standards of radiation oncologists in evaluating and treating adenocarcinoma of the rectum and sigmoid colon.

MATERIALS AND METHODS

A national survey of 73 institutions using two-stage cluster sampling was conducted, and specific information on 408 patients from 69 facilities with adenocarcinoma of the rectum and sigmoid colon who received radiation as part of definitive or adjuvant management was collected.

RESULTS

Using the modified Astler-Coller (MAC) pathologic staging system, the stage distribution was as follows: A, 0.5%; B1, 4.4%; B2, 23.5%; B3, 5.1%; C1, 8.9%; C2, 30.2%; and C3, 6.6%. Preoperative radiation was used in 29% of patients, but the total dose was greater than 40 Gy in only 20%. Seventy-three percent of patients received postoperative radiation, with approximately 4% receiving combined preoperative and postoperative radiation. Chemotherapy was administered to 44% of patients overall, representing 55% of patients with disease through the bowel wall and/or involving lymph nodes. Only 37% of all patients received chemotherapy concurrent with radiation. An abdominoperineal resection was used in 43%; a low anterior resection was used in 43% as well, while 5% underwent other types of bowel resection. Approximately 8% of patients were treated with a local curative procedure less than bowel resection (eg, local excision, endoscopic resection, fulguration, or contact radiation). At least one third of patients had interruption in their pelvic irradiation of greater than 3 days. There was no statistically significant difference in the frequency of treatment interruptions by dose per fraction or whether chemotherapy was given concurrent with radiation. There was no significant difference in total dose delivered to patients staged B2 and higher treated without chemotherapy compared with concurrent chemotherapy and radiation. Also, there was no significant difference in total dose delivered to patients with B1 and B2, or C1 and C2 versus B3 or C3 cancer.

CONCLUSION

This study was conducted on patients treated just before the 1990 National Institutes of Health consensus guidelines issued on the management of colon and rectal cancer. This study indicates that the minority of patients treated with radiation in 1988 and 1989 received concurrent chemoradiation, as currently recommended. Additionally, insofar as present studies are investigating important issues such as the use of sphincter-sparing procedures, preoperative radiation and chemotherapy, and the importance of radiation dose and scheduling with chemotherapy, the information provided by this study will serve as a useful baseline to track future changes in rectal cancer evaluation and management.
A prospective randomized trial of adjuvant brachytherapy in the management of low-grade soft tissue sarcomas of the extremity and superficial trunk.
Authors: Pisters P W , Harrison L B , Woodruff J M , Gaynor J J , Brennan M F
Published: February 2017

PURPOSE

This study was designed to evaluate the impact of adjuvant brachytherapy (BRT) on local and systemic recurrence rates in patients with low-grade sarcoma.

PATIENTS AND METHODS

Forty-five patients with histologic low-grade, completely resected soft tissue sarcomas of the extremity or superficial trunk were entered onto this trial. Following resection of all gross disease, patients were randomized to the BRT arm (n = 22) or to the no-BRT arm (n = 23). On the fifth or sixth postoperative day, catheters were loaded with iridium 192 to deliver a dose of 45 Gy to the tumor bed over 4 to 6 days.

RESULTS

The two groups were evenly distributed with respect to the distribution of presentation status (primary v recurrent), tumor site (trunk v extremity, proximal v distal extremity), tumor size (< 5 cm v > or = 5 cm), tumor depth (superficial v deep), and microscopic tumor margins (positive v negative). The predominant histopathologic diagnosis in each group was liposarcoma (BRT, 13 of 22 [59%]; no BRT, 14 of 23 [61%]) with other histopathologic subtypes evenly distributed between the two groups. The median follow-up duration among the ongoing survivors is 67 months. One patient in the BRT group developed systemic disease and died of progressive disease. Local recurrence occurred in five of 23 patients (22%) in the no-BRT group and six of 22 patients (27%) in the BRT group (P = .60).

CONCLUSION

Adjuvant radiation in the form of BRT does not appear to decrease local recurrence rates following complete resection of low-grade extremity and superficial trunk soft tissue sarcomas. Other adjuvant approaches, such as external-beam radiotherapy, are required to have a significant impact on local recurrence rates in this group of patients.
Use of retinoic acids in the treatment of peripheral T-cell lymphoma: a pilot study.
Authors: Cheng A L , Su I J , Chen C C , Tien H F , Lay J D , Chen B R , Pu Y S , Hong R L , Shen M C , Wang C H
Published: February 2017

PURPOSE

We have systemically analyzed, both in vitro and in vivo, the effect of 13-cis-retinoic acids (RA) on non-Hodgkin's lymphoma (NHL).

METHODS

The in vitro growth-inhibitory effect of 13-cis-RA was examined in 11 (T cell, five; B cell, six) lymphoma cell lines by a tetrazolium colorimetric assay. A pilot clinical trial with oral 13-cis-RA 1 mg/kg/d was conducted in a selected group of 18 lymphoma patients, of whom 16 had failed to respond to at least one regimen of intensive chemotherapy. The in vitro and in vivo effects of 13-cis-RA were correlated with immunophenotypes, RA-induced changes of morphology, and patterns of DNA fragmentation of the lymphoma cells.

RESULTS

Four of five T-lymphoma cell lines and none of six B-lymphoma cell lines were sensitive (concentration of 50% growth inhibition [IC50] < 1.5 microns) to 13-cis-RA (P = .015). In the clinical trial, five (two Ki-1, one angioinvasive type, one diffuse mixed cell, and one diffuse large cell) complete remissions and one (Ki1) partial remission were observed in 12 patients with peripheral T-cell lymphoma (PTCL), while none of six patients with B-cell lymphoma responded to 13-cis-RA. 13-cis-RA-induced cellular differentiation and apoptosis, as evidenced by the more mature morphology, characteristic nuclear condensation, and DNA ladder pattern signifying internucleosomal fragmentation, were demonstrated in the sensitive cell lines, as well as in the remitting lymphoma tissues.

CONCLUSION

The 13-cis-RA appears to be active on lymphomas of T-lineage and their therapeutic indication may be extended to include some subtypes of PTCL. The mechanisms of action are related to differentiation and apoptosis of lymphoma cells. There appears to be no cross-resistance between 13-cis-RA and conventional chemotherapy.
Antibody targeting in metastatic colon cancer: a phase I study of monoclonal antibody F19 against a cell-surface protein of reactive tumor stromal fibroblasts.
Authors: Welt S , Divgi C R , Scott A M , Garin-Chesa P , Finn R D , Graham M , Carswell E A , Cohen A , Larson S M , Old L J
Published: February 2017

PURPOSE

To define the toxicity, imaging, and biodistribution characteristics of iodine 131-labeled monoclonal antibody F19 (131I-mAbF19). MAbF19 recognizes the fibroblast activation protein (FAP), a cell-surface glycoprotein not present in most normal tissues, but abundantly expressed by reactive stromal fibroblasts of epithelial cancers, including more than 95% of primary and metastatic colorectal carcinomas.

PATIENTS AND METHODS

131I-mAbF19 was administered intravenously to 17 patients with hepatic metastases from colorectal carcinoma who were scheduled for resection of localized metastases or insertion of hepatic artery catheter for regional chemotherapy. Seven to 8 days before surgery, patients received 131I-mAbF19 at three dose levels, with at least four patients entered at each level.

RESULTS

No toxicity associated with intravenous 131I-mAbF19 administration was observed. Tumor images were obtained on planar and single-photon emission tomography (SPECT) scans in 15 of 17 patients with hepatic metastases, tumor-infiltrated portal lymph nodes, and/or recurrent pelvic disease. The smallest lesion visualized was 1 cm in diameter. The optimal time for tumor imaging was 3 to 5 days after 131I-mAbF19 administration. The use of image registration techniques allowed precise anatomic localization of 131I-mAbF19 accumulation. Immunohistochemical analysis of biopsy tissues showed expression of FAP in the tumor stroma (but not in normal liver) in all patients studied and confirmed that the FAP-positive tumor stromal fibroblasts were interposed between the tumor capillaries and the malignant colon epithelial cells. At the time of surgery, tumor-to-liver ratios up to 21:1 and tumor-to-serum ratios up to 9:1 were obtained. The fraction of the injected 131I-mAbF19 dose per gram tumor (%ID/g tumor) localized to hepatic metastases at the time of surgery ranged from 0.001% to 0.016%.

CONCLUSION

The FAP tumor fibroblast antigen is highly expressed in primary and metastatic colorectal carcinomas and shows limited expression in normal adult tissues. This highly selective expression pattern allows imaging of colorectal carcinoma lesions as small as 1 cm in diameter on 131I-mAbF19 scans. Because of the consistent presence of FAP in the stroma of epithelial cancers and the accessibility of FAP-positive tumor stromal fibroblasts to circulating monoclonal antibodies (mAbs), this study suggests possible diagnostic and therapeutic applications of humanized mAbF19 and mAbF19 constructs with novel immune and nonimmune effector functions.
Phase II trial of docetaxel in patients with stage III and IV non-small-cell lung cancer.
Authors: Francis P A , Rigas J R , Kris M G , Pisters K M , Orazem J P , Woolley K J , Heelan R T
Published: February 2017

PURPOSE

This phase II study was conducted to evaluate the efficacy and toxicity of docetaxel in the treatment of patients with advanced non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS

Docetaxel was administered to 29 patients with unresectable stage III and IV NSCLC at a dose of 100 mg/m2 intravenously (IV) over 1 hour every 21 days. No premedication was given to the first 16 patients. Premedication with diphenhydramine was instituted for the remainder. No patient had previously received chemotherapy. Seven patients had undergone prior radiation therapy.

RESULTS

All patients were assessable for response and toxicity. Eleven of 29 patients (38%) had a major objective response (95% confidence interval, 21% to 58%). The median duration of response was 5.3 months. Febrile neutropenia occurred in 41% of patients and in 11% of 134 courses of docetaxel. Nonhematologic toxicities included infusion-related hypersensitivity reactions, fluid retention, rash, alopecia, and sensory neuropathy. Premedication with diphenhydramine did not decrease the incidence of infusion-related hypersensitivity reactions.

CONCLUSION

At this dose and schedule, docetaxel demonstrates significant antitumor activity in patients with advanced NSCLC. Further investigations of this agent in NSCLC are indicated.
Relationship between fluorouracil systemic exposure and tumor response and patient survival.
Authors: Milano G , Etienne M C , Renée N , Thyss A , Schneider M , Ramaioli A , Demard F
Published: February 2017

PURPOSE

The aim of this study was to analyze the link between fluorouracil (FU) systemic exposure and tumor response and overall survival.

PATIENTS AND METHODS

One hundred eighty-six patients (162 men, 24 women) with head and neck cancer were studied. All received cisplatin plus FU for three cycles as first-line chemotherapy. The treatment consisted of cisplatin (100 mg/m2 intravenously [IV]) followed by a 5-day continuous venous infusion of FU (1 g/m2/d). The median follow-up duration for the 104 patients alive was 24 months. For each cycle, we calculated the area under the curve over the duration of pharmacokinetic follow-up (AUC0-105 h) for plasma FU. For each patient, we analyzed the averaged AUC0-105 h and the averaged total dose for the three cycles.

RESULTS

The response rate was 30% complete responses (CRs), 22% partial responses (PRs) more than 75%, 25% PRs less than 75%, and 23% no response (NR). Medians for averaged AUC and dose per cycle were 27,906 ng/mL h (first through third quartile, 25,398 to 31,060) and 7,000 mg (first through third quartile, 6,200 to 7,833), respectively. The tumor response was significantly linked to tumor stage (P < .001) and to averaged AUC (P = .05), but not to averaged dose. Analysis of parameters (continuous variable) expressing FU treatment intensity showed that dose did not influence survival contrary to the AUC (P = .001). The AUC remains significant (P = .025) in a multivariate analysis including tumor stage, demonstrating that the greater the FU systemic exposure, the longer the survival.

CONCLUSION

These results strengthen the interest of individual FU dose adaptation based on pharmacokinetics.
High-dose therapy and autologous bone marrow transplantation for adult patients with lymphoblastic lymphoma: results of the European Group for Bone Marrow Transplantation.
Authors: Sweetenham J W , Liberti G , Pearce R , Taghipour G , Santini G , Goldstone A H
Published: February 2017

PURPOSE

To investigate the results of treatment and factors that affect prognosis in adult patients undergoing high-dose therapy and autologous bone marrow transplantation (ABMT) for lymphoblastic lymphoma (LBL).

PATIENTS AND METHODS

The study was a retrospective analysis of 214 patients reported to the Lymphoma Registry of the European Group for Bone Marrow Transplantation (EBMT) between January 1981 and December 1992, including 105 patients undergoing marrow transplantation in first complete remission (CR). Data on all patients were reviewed, and analysis of prognostic factors conducted.

RESULTS

The actuarial overall survival rate at 6 years for the entire group is 42%. Disease status at ABMT was the major determinant of outcome: 6-year actuarial overall survival was 63% for patients transplanted in first CR, compared with 15% for those with resistant disease at the time of transplantation. Transplantation in second CR resulted in a 31% rate of actuarial overall survival at 6 years. For patients transplanted in first CR, univariate analysis failed to identify any factors at presentation that predicted for outcome after transplantation.

CONCLUSION

These results suggest that ABMT is effective therapy for adults with LBL, even in patients with disease that is resistant to conventional-dose therapy. Results for patients transplanted in second CR are superior to those reported for conventional-dose salvage regimens. The results in first CR require verification in a prospective randomized clinical study.
MACOP-B versus ProMACE-MOPP in the treatment of advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group.
Authors: Sertoli M R , Santini G , Chisesi T , Congiu A M , Rubagotti A , Contu A , Salvagno L , Coser P , Porcellini A , Vespignani M
Published: February 2017

PURPOSE

The aim of our study was to compare in a multicentric randomized trial two regimens widely used in the treatment of advanced-stage intermediate- to high-grade non-Hodgkin's lymphoma and to assess whether a third-generation regimen (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) was superior to a second-generation regimen (procarbazine, methotrexate with leucovorin, doxorubicin, cyclophosphamide, and etoposide [ProMACE-MOPP]).

PATIENTS AND METHODS

Between January 1987 and August 1991, 221 patients with diffuse intermediate- to high-grade non-Hodgkin's lymphoma (Working Formulation groups F, G, H, and K), stage II bulky (> 10 cm), III, or IV, were randomized by the Non-Hodgkin's Lymphoma Cooperative Study Group (NHLCSG) to receive ProMACE-MOPP for six cycles or MACOP-B for 12 weeks. Survival, progression-free survival, and disease-free survival were determined, and multivariate analysis of prognostic factors was performed.

RESULTS

In the two groups of patients, there was no significant difference in terms of complete remission (CR) rate (49.1% with ProMACE-MOPP and 52.3% with MACOP-B), 3-year overall survival rate (45.2% with PROMACE-MOPP and 52.3% with MACOP-B), and 3-year progression-free survival rate (36.4% with ProMACE-MOPP and 36.1% with MACOP-B). In terms of toxicity, no significantly greater toxicity occurred in either arm. Overall toxicity was acceptable. The most frequent side effects were grade II through IV leukopenia, infection, mucositis, and anemia. Treatment-related deaths were equally distributed.

CONCLUSION

No significant differences in terms of efficacy and/or toxicity between ProMACE-MOPP and MACOP-B are evident. These results are consistent with recent randomized trials showing that the new-generation aggressive regimens are no better than previous ones.
Phase I study of oral etoposide in children with refractory solid tumors.
Authors: Mathew P , Ribeiro R C , Sonnichsen D , Relling M , Pratt C , Mahmoud H , Bowman L , Meyer W , Avery L , Crist W
Published: February 2017

PURPOSE

To determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and plasma concentrations of orally administered etoposide (VP-16) in pediatric oncology patients.

PATIENTS AND METHODS

In a phase I study, 20 children with refractory solid tumors received oral VP-16 (the intravenous preparation diluted with sodium chloride) three times daily for 21 days. Daily dose levels studied were 50 mg/m2 (n = 5), 60 mg/m2 (n = 7), and 75 mg/m2 (n = 8). VP-16 concentrations were measured in blood samples collected on days 1, 7, 14, and 21.

RESULTS

Grade 3 to 4 thrombocytopenia and/or neutropenia causing interruption of the 21-day course or persisting for more than 7 days after the last day of chemotherapy was seen at all dose levels, but was not dose-limiting. One patient treated at the 50-mg/m2 daily dose died of sepsis. At the 75-mg/m2 dose level, diarrhea was dose-limiting. Estimated plasma VP-16 concentrations were greater than 1 micrograms/mL for median periods of 9.4, 15.4, and 13.5 hours per day at daily doses of 50, 60, and 75 mg/m2, respectively. Responses were observed in seven of 14 patients who received at least one additional course of etoposide after a rest period of 7 days. There was one complete and two objective responses. Four patients were considered to have stable disease.

CONCLUSION

The intravenous preparation of VP-16 administered orally appears to be well tolerated by heavily pretreated pediatric patients. On the three-times daily, 21-day schedule, a daily dose of 75 mg/m2 exceeds the MTD, with diarrhea as the dose-limiting toxicity. The recommended dose for oral etoposide is 60 mg/m2/d administered every 8 hours.
In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2.
Authors: Schwartzentruber D J , Hom S S , Dadmarz R , White D E , Yannelli J R , Steinberg S M , Rosenberg S A , Topalian S L
Published: February 2017

PURPOSE

To correlate in vitro characteristics of tumor-infiltrating lymphocytes (TIL) with clinical response to TIL immunotherapy in patients with metastatic melanoma.

PATIENTS AND METHODS

Forty-one melanoma patients undergoing 43 separate treatment courses with TIL and interleukin-2 (IL-2) from December 1990 through November 1992 were studied prospectively. Multiple patient and treatment characteristics were evaluated for response correlates. In addition, TIL were assayed within 7 days of infusion for characteristics such as doubling time, cell-surface phenotype, autologous tumor lysis in 4-hour chromium-51 release assays, and cytokine secretion following autologous tumor stimulation.

RESULTS

Nine patients experienced complete or partial tumor regressions. Clinical parameters such as age, sex, sites of disease, performance status, and prior therapies were similar in responders and nonresponders. Treatment variables such as the cumulative IL-2 dose and concomitant administration of cyclophosphamide or interferon (IFN)-alpha were not predictive of response, although responders received 33% more TIL. However, statistically significant differences in favor of clinical response were noted for extranodal source of TIL (v lymph node), shorter culture duration (mean, 38 v 47 days), shorter TIL doubling time (2.6 v 3.7 days), greater autologous tumor lysis by TIL (30% v 15%; effector-to-target [E:T], 40:1), and secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) by TIL following autologous tumor stimulation (six of nine responders v eight of 32 nonresponders).

CONCLUSION

The associations of TIL lysis of autologous tumor and younger TIL age with clinical response observed in this study are supportive of previous reports, and these findings will be useful in designing future clinical trials. The new observation correlating GM-CSF secretion by TIL with clinical response is interesting and needs further substantiation.
Non-Hodgkin's lymphoma of the gastrointestinal tract: a population-based analysis of incidence, geographic distribution, clinicopathologic presentation features, and prognosis. Danish Lymphoma Study Group.
Authors: d'Amore F , Brincker H , Grønbaek K , Thorling K , Pedersen M , Jensen M K , Andersen E , Pedersen N T , Mortensen L S
Published: February 2017

PURPOSE

To evaluate incidence, time trends, geographic distribution, clinicopathologic presentation features, and prognostic factors for survival and relapse in gastrointestinal (GI) non-Hodgkin's lymphomas (NHLs).

PATIENTS AND METHODS

Over a 9-year period (1983 to 1991), 2,446 new NHL cases were recorded in a Danish population-based NHL registry (Danish Lymphoma Study Group [LYFO]). Of these, 306 (12.5%) were GI NHL (175 gastric, 109 intestinal, and 22 both sites). LYFO registry data were used for incidence rate (IR) assessment, and time-trend and geographic distribution analysis. Relative risk (RR) values for survival and relapse were identified by multivariate analysis.

RESULTS

The mean annual, age-standardized IRs for gastric and intestinal NHL were 0.71/10(5) and 0.48/10(5) per year, respectively. Age-specific IRs for both localizations showed an exponential increase as a function of age. Time-trend analysis for the period 1983 to 1991 showed stable IRs for both localizations. Intestinal NHL was more frequent in males (male-to-female ratio, 2.0 v 1.3), and had a higher occurrence of disseminated disease, constitutional symptoms, high-grade histology, and T-cell phenotype (10% v 2%). Gastric NHL had more low-grade cases (38% v 19%), and almost all were of the mucosa-associated lymphoid tissue (MALT) type. The cause-specific 5-year survival rate was 63% for gastric NHL and 49% for intestinal NHL. The Musshoff staging system was an excellent discriminator between truly localized (stage I and II1) and disseminated cases (stage II2 to IV), particularly for gastric NHL, for which no survival difference was found between surgically and conservatively stage localized cases.

CONCLUSION

(1) No increase in the incidence of GI NHL was found over a 9-year observation period; (2) nonrandom spatial distribution of new GI NHL cases was observed; (3) factors that significantly increased the risk of death in gastric cases were presence of B symptoms (RR = 3.3), clinical stage is more than II1 (RR = 3.0), age more than 72 years (RR = 2.4), and elevated serum lactate dehydrogenase (s-LDH) level (RR = 2.0); and factors that increased the risk of death in intestinal cases were presence of B symptoms (RR = 3.2), age more than 58 years (RR = 2.8), and clinical stage more than I (RR = 2.1); (4) factors that significantly increased the risk of relapse in gastric cases were male sex and no radiotherapy in primary treatment; and in intestinal cases were T-cell phenotype and no surgery in primary treatment; (5) surgical staging, as opposed to thorough noninvasive staging, did not improve staging accuracy and final outcome in localized gastric NHL.
Quantitating familial cancer risk: a resource for clinical oncologists.
Authors: Offit K , Brown K
Published: February 2017

PURPOSE

Because a family history of cancer constitutes an important risk factor, estimation and communication of cancer risk can facilitate efforts toward early detection and prevention. This review provides a resource for health professionals called to draw upon a multidisciplinary literature to provide quantitative risk estimates to families with cancer.

DESIGN

Descriptive population-derived, epidemiologic, genetic, genetic epidemiologic, and molecular studies are critically reviewed in the context of cancer genetic counseling.

RESULTS

Data are presented that document the increased lifetime relative risk to relatives of individuals with cancers of the breast, ovary, colon, prostate, or other sites. In general, risk ratios are poorly suited for clinical counseling. Age-specific absolute risks are presented for first-degree relatives of individuals affected by cancers of the breast, ovary, and colon. The derivation of Mendelian and Bayesian risk estimates in the setting of well-defined cancer family syndromes, and the growing role of DNA testing in more accurately assessing these risks, are discussed. Such carrier testing requires careful psychologic and ethical considerations.

CONCLUSION

Multidisciplinary cancer genetic counseling is an emerging resource available to physicians who care for families with common adult malignancies.
Pulmonary metastases of stage IIB extremity osteosarcoma and subsequent pulmonary metastases.
Authors: Ward W G , Mikaelian K , Dorey F , Mirra J M , Sassoon A , Holmes E C , Eilber F R , Eckardt J J
Published: February 2017

PURPOSE

This study investigated prognostic factors in nonmetastatic high-grade extremity osteosarcoma and the prognosis following resection of subsequent pulmonary metastases, with emphasis on the effect of chemotherapy-induced tumor necrosis.

PATIENTS AND METHODS

We reviewed 111 consecutive patients with high-grade nonmetastatic extremity osteosarcoma treated with preoperative chemotherapy and surgical resection, with additional review of 36 patients who had subsequent pulmonary metastases resected.

RESULTS

The overall 5-year survival rate was 53%. In resected primary tumors, tumor-free resection margin (P < .001) and increasing chemotherapy-induced tumor necrosis (> 90% threshold, P < .003) correlated with increased metastasis-free survival. Relative risk factors for metastases were as follows: tumor-containing resection margin (most likely to metastasize); poor response to preoperative chemotherapy and/or lack of postoperative chemotherapy (next worse prognosis); and excellent response to preoperative chemotherapy (> or = 90% necrosis) combined with postoperative chemotherapy (best prognosis). The 5-year survival rate following pulmonary metastasis resection was 23%, whereas a 0% 4-year survival rate followed development of bony metastases (P < .001). The extent of tumor necrosis in resected pulmonary metastases did not affect prognosis. Survival was best in patients with three or fewer pulmonary nodules (P < .048), four or fewer recurrent pulmonary nodules (P < .047), unilateral pulmonary metastases (P < .037), or longer intervals between primary tumor resection and metastases (P < .082).

CONCLUSION

Intensive preoperative and postoperative chemotherapy combined with complete resection of both primary and metastatic pulmonary osteosarcomas is justified, with a goal of 100% tumor necrosis and excision. Although current treatment regimens allow effective salvage therapy for a few patients with pulmonary metastases, more effective systemic treatment is needed.
Very low-dose warfarin prophylaxis to prevent thromboembolism in women with metastatic breast cancer receiving chemotherapy: an economic evaluation.
Authors: Rajan R , Gafni A , Levine M , Hirsh J , Gent M
Published: February 2017

PURPOSE

A recent double-blind, randomized trial demonstrated that very low-dose warfarin (VLDW) reduced the incidence of venous thromboembolism (VTE) without increasing the rate of bleeding in women with metastatic breast cancer receiving chemotherapy. We have evaluated the economic impact on the health care system of using VLDW in such patients.

METHODS

The records of patients entered onto the trial and a simultaneous, fully allocated, costing model for a tertiary care hospital in Hamilton, Canada were used to determine the difference in costs associated with the care of patients with and without VLDW.

RESULTS

The cost of providing VLDW was $ 21,854 (Canadian dollars) per 100 patients. This therapy led to a reduction in costs of $ 24,297 per 100 patients, thus saving the health care system $ 2,443 per 100 patients. In the sensitivity analysis, VLDW prophylaxis still did not increase health care costs unless the cost of VLDW was greatly increased, the cost of treating thromboembolic episodes was markedly reduced, or the incidence of either VTE or bleeding with VLDW was increased above the rates observed in the trial.

CONCLUSION

We conclude that for women receiving chemotherapy for metastatic breast cancer, the benefits of VLDW can be realized without increased health care costs.
Prognostic significance of early serum tumor marker half-life in metastatic testicular teratoma.
Authors: Stevens M J , Norman A R , Dearnaley D P , Horwich A
Published: February 2017

PURPOSE

To determine whether the initial regression rates of serum tumor marker concentration (alpha-fetoprotein [AFP] and beta-human chorionic gonadotrophin [HCG]) were important prognostic factors after chemotherapy for germ cell tumors.

PATIENTS AND METHODS

The analysis was confined to patients with at least two precise marker assay results between days 7 and 22 from start of platinum-based combination chemotherapy, with at least 7 days between markers. One hundred eighty-three patients were eligible and marker half-life (MHL) was evaluated for AFP in 142 and for HCG in 111 cases. MHL was calculated from the following formula: MHL = Ln1/2/G, where G was the gradient of the marker slope on a plot of Ln marker concentration versus time. MHL was regarded as prolonged if more than 3 days for HCG or more than 7 days for AFP.

RESULTS

The median AFP MHL was 6 days (range, 2.7 to 237) and the median HCG MHL was 2.6 days (range, 1.7 to 37.5). Forty-nine of 142 patients (35%) had a prolonged AFP MHL; 39 of 111 patients (35%) had a prolonged HCG-MHL. A prolonged MHL did not identify relapse after front-line chemotherapy. The positive predictive value of MHL tests in identifying patients who progressed after front-line therapy was 18% for HCG, 20% for AFP, and 18% for either marker. A prolonged MHL did indicate a higher risk of mortality (hazards ratio [HR], 2.4; P = .016), but again the positive predictive value of this test was only 23%.

CONCLUSION

Early evaluation of MHL by this method does not predict patients at higher risk of progression after front-line chemotherapy, and also is a poor guide to long-term prognosis.
Anaphylactoid reactions in children receiving high-dose intravenous cyclosporine for reversal of tumor resistance: the causative role of improper dissolution of Cremophor EL.
Authors: Theis J G , Liau-Chu M , Chan H S , Doyle J , Greenberg M L , Koren G
Published: February 2017

PURPOSE

An unusually high incidence of anaphylactoid reactions was observed during a phase I/II trial of high-dose intravenous cyclosporine (CsA) therapy to attenuate tumor multidrug resistance (MDR). Five of 21 children experienced severe anaphylactoid reactions shortly after initiation of the first or second CsA infusion. We hypothesized that improper dissolution of the vehicle Cremophor EL may have been a cause for these anaphylactoid reactions.

METHODS

All nurses who had administered intravenous CsA were interviewed regarding their technique of preparing the infusion and the occurrence of an anaphylactoid reaction. The responses were statistically analyzed. The effect of various mixing techniques on the distribution of Cremophor EL in the infusion was experimentally evaluated. Different mixing techniques were used to assess their effect on the distribution of Cremophor EL in the solution.

RESULTS

Analysis of the preparation techniques of the CsA infusion showed significant correlation between suboptimal mixing of CsA by nurses and the occurrence of anaphylactoid reactions (P = .02). Experimental simulation showed that suboptimal mixing results in an uneven distribution of Cremophor EL, which subsequently sinks to the bottom of the vial.

CONCLUSION

Improper mixing of high-dose CsA infusions causes nonsolubilized Cremophor EL to sink to the outflow area of the bottle. An initial bolus infusion of highly concentrated Cremophor EL may produce an anaphylactoid-like response. This mechanism of toxicity is important to recognize, because it is easily preventable by proper preparation of the infusion, thus reducing the incidence of potentially life-threatening anaphylactoid reactions.
Etoposide and cisplatin adjuvant therapy for patients with pathologic stage II germ cell tumors.
Authors: Motzer R J , Sheinfeld J , Mazumdar M , Bajorin D F , Bosl G J , Herr H , Lyn P , Vlamis V
Published: February 2017

PURPOSE

Two options cure nearly all patients with pathologic stage II nonseminomatous germ cell tumors (NSGCTs): two cycles of adjuvant chemotherapy with cisplatin, vinblastine, and bleomycin (PVB) or cisplatin, vinblastine, bleomycin, cyclophosphamide, and dactinomycin (VAB-6); or close observation with full treatment at relapse. Two cycles of etoposide plus cisplatin (EP) were given to selected patients with pathologic stage II NSGCT and high-volume nodal metastases.

PATIENTS AND METHODS

All patients had pathologic stage II NSGCT with one or more of the following features found at retroperitoneal lymph node dissection (RPLND), suggesting a greater than 50% likelihood of relapse after observation alone: (1) any lymph node involved by tumor greater than 2 cm (stage N2b); (2) > or = six nodes involved with tumor (stage N2b); and (3) extranodal extension (stage N3). Two cycles of therapy were given at 21-day intervals; each cycle consisted of etoposide 100 mg/m2 plus cisplatin 20 mg/m2 per day given on days 1 to 5.

RESULTS

Fifty patients were treated with two cycles of EP. Treatment was well tolerated; five patients (10%) were admitted for nadir fever and none had grade II or greater neurologic, renal, or pulmonary toxicity. All 50 patients are alive and relapse-free at a median follow-up time of 35 months (range, 12 to 72). The follow-up duration has been > or = 2 years for 42 patients.

CONCLUSION

A treatment program that consists of two cycles of EP is effective in preventing relapses in patients with completely resected pathologic stage N2b and N3 NSGCT. The likelihood of relapse without adjuvant cisplatin-containing chemotherapy in this group has been shown to be greater than 50%. As has been demonstrated in patients with disseminated germ cell tumor (GCT), EP can be considered a therapeutic option in the adjuvant setting for completely resected N2b and N3 NSGCT.
Testicular germ cell tumors and human immunodeficiency virus infection: a report of 26 cases. Italian Cooperative Group on AIDS and Tumors.
Authors: Bernardi D , Salvioni R , Vaccher E , Repetto L , Piersantelli N , Marini B , Talamini R , Tirelli U
Published: February 2017

PURPOSE

Besides tumors that are diagnostic of AIDS, such as non-Hodgkin's lymphoma, Kaposi's sarcoma, and invasive carcinoma of the cervix, other tumors have been described in the human immunodeficiency virus (HIV) setting. Some case reports on testicular cancer in HIV-infected patients have appeared in the literature. We present a retrospective study on 26 cases of testicular germ cell tumors (TGCTs) observed within the Italian Cooperative Group on AIDS and Tumors (GICAT) between November 1986 and September 1994.

PATIENTS AND METHODS

Twenty-six patients with TGCT and HIV-infection from the GICAT were retrospectively analyzed.

RESULTS

Fourteen patients had seminoma and 12 had nonseminoma. Four patients underwent only orchidectomy, one patient received only chemotherapy, nine patients were treated with postsurgical chemotherapy, 10 patients (38%) received postsurgical radiotherapy, one patient received postsurgical chemotherapy plus radiotherapy, and one patient was lost for follow-up evaluation immediately after diagnosis. The complete response (CR) rate was 95%. Relapse occurred in 32% of patients. The median follow-up time was 33 months. The mortality rate was 37%. Causes of death were neoplasia in three of nine patients, AIDS in five of nine patients, and fortuitous event in one of nine patients. The overall 3-year survival rate was 65%, and the 3-year disease-free survival rate was 65%. Severe hematologic toxicity was observed in seven of 15 patients.

CONCLUSION

HIV-infected patients with testicular cancer should be offered standard oncologic therapy, irrespective of their HIV status, since the majority can be cured of their tumor and have a good quality of life. Use of concomitant prophylaxis for opportunistic infections is recommended.