bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormalities of chromosome 16 in association with acute myelomonocytic leukemia and dysplastic bone marrow eosinophils.
Authors: Hogge D E , Misawa S , Parsa N Z , Pollak A , Testa J R
Published: February 2017

Six patients with M4 acute myelomonocytic leukemia ( AMMoL ) were identified who had abnormalities of chromosome 16 in bone marrow cells. Five had a pericentric inversion, inv(16)( p13q22 ), and a sixth patient had a translocation, t(16;16)(p13.1;q22). Each of these six patients had bone marrow eosinophils that were abnormal in morphology on light and/or electron microscopy and by cytochemical stains. The eosinophils constituted 1%-24% of nucleated marrow cells. Of 61 acute nonlymphocytic leukemia (ANLL) patients, all those with AMMoL and abnormal bone marrow eosinophils had an inv(16) or a t(16;16). One other patient in this group had a rearrangement of chromosome 16 (with a break in the short arm at band p13); however, the ANLL type was M1 and no abnormal eosinophils were present. Four patients with ANLL types other than M4 had an increase in marrow eosinophils; three in whom the eosinophils appeared normal and one with ANLL-M2 and bizarre eosinophils morphologically distinct from those seen in AMMoL . Chromosome pair 16 was normal in the latter four patients. AMMoL with dysplastic bone marrow eosinophils appears to represent a unique clinicopathologic entity associated with several related abnormalities affecting 16q . The morphologic features of both blasts and eosinophils may be more important than the absolute number of eosinophils in the marrow in identifying this group of patients. This may have prognostic importance as five of six patients achieved complete remission with standard antileukemic therapy and are still alive.
The clinical significance of radiographically detected pulmonary neoplastic lesions in patients with head and neck cancer.
Authors: Malefatto J P , Kasimis B S , Moran E M , Wuerker R B , Stein J J
Published: February 2017

The histopathologic features of pulmonary lesions found in 36 patients with head and neck cancer ( HNC ) whose chest radiograms had abnormalities suggestive of a neoplasm were reviewed. Ten patients (28%) had benign lesions but cancer was diagnosed in 26 patients (72%) by lung biopsy or at autopsy. Second primary lung cancer was found in 19 (53%) and metastatic HNC in seven (19%) of the 36 patients examined. The second lung primaries occurred in seven (100%) patients with HNC in stage I or II and in 12 (63%) of those in stage III or IV. The histologic examination revealed squamous cell carcinoma of the lung in eight (42%) of 19 patients, small cell carcinoma in six (31.5%), adenocarcinoma in three (16%), and large-cell carcinoma in two (10.5%). These findings indicate that a prompt histologic examination of radiographically detected neoplastic pulmonary lesions in patients who have, or have had HNC is mandatory because a second primary cancer of the lung may be found and cured with early treatment. Furthermore, a substantial number of the patients in this retrospective analysis had small-cell carcinoma of the lung and could benefit from current therapeutic advances for this type of tumor.
Accuracy of computerized tomography in determining hepatic tumor size in patients receiving liver transplantation or resection.
Authors: Mittal R , Kowal C , Starzl T , Van Thiel D , Bron K , Iwatsuki S , Schade R , Straub W , Dekker A
Published: February 2017

Computerized tomography (CT) of liver is used in oncologic practice for staging tumors, evaluating response to treatment, and screening patients for hepatic resection. Because of the impact of CT liver scan on major treatment decisions, it is important to assess its accuracy. Patients undergoing liver transplantation or resection provide a unique opportunity to test the accuracy of hepatic-imaging techniques by comparison of findings of preoperative CT scan with those at gross pathologic examination of resected specimens. Forty-one patients who had partial hepatic resection (34 patients) or liver transplantation (eight patients) for malignant (30 patients) or benign (11 patients) tumors were evaluable. Eight (47%) of 17 patients with primary malignant liver tumors, four (31%) of 13 patients with metastatic liver tumors, and two (20%) of 10 patients with benign liver tumors had tumor nodules in resected specimens that were not apparent on preoperative CT studies. These nodules varied in size from 0.1 to 1.6 cm. While 11 of 14 of these nodules were less than 1.0 cm, three of 14 were greater than 1.0 cm. These results suggest that conventional CT alone may be insufficient to accurately determine the presence or absence of liver metastases, extent of liver involvement, or response of hepatic metastases to treatment.
Randomized trial of cyclophosphamide, doxorubicin, and 5-fluorouracil alone or alternating with a "cycle active" non-cross-resistant combination in women with visceral metastatic breast cancer: a Southeastern Cancer Study Group project.
Authors: Vogel C L , Smalley R V , Raney M , Krauss S , Carpenter J , Velez-Garcia E , Fishkin E , Raab S , Moore M R , Stagg M
Published: February 2017

Patients with visceral patterns of metastatic breast cancer were stratified according to dominant metastatic site and performance status and then randomized to therapy with cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) or CAF alternating with a "cell-cycle active" regimen including cytosine arabinoside, methotrexate with leucovorin rescue, and oncovin ( CAMELEON ). One hundred eighty-seven patients were randomized; response rate for CAF was 44% and for CAF + CAMELEON , 40%. Durations of disease control and survival were not significantly different. Toxicity of CAF was as anticipated with predominant granulocytopenia, vomiting, and alopecia. Toxicity of CAMELEON was less severe than that of CAF, and CAF toxicity was not worsened by preceding courses of CAMELEON ; however, the CAF- CAMELEON regimen was cumbersome and complex leading to both physician and patient noncompliance. Contrary to the preliminary results of a pilot study, and preliminary reports of the present trial suggesting benefit for the CAF- CAMELEON regimen the present randomized trial does not confirm any significant benefit of CAF- CAMELEON over CAF alone in patients with visceral metastatic breast cancer although this conclusion must be viewed in light of the high inevaluability rate due to patient and physician noncompliance.
Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26.
Authors: Shafford E A , Rogers D W , Pritchard J
Published: February 2017

Forty-two children, all over one year of age, were given vincristine, cyclophosphamide, and sequentially timed cisplatin and VM-26 (OPEC) or OPEC and doxorubicin (OPEC-D) as initial treatment for newly diagnosed stage III or IV neuroblastoma. Good partial response was achieved in 31 patients (74%) overall and in 28 (78%) of 36 patients whose treatment adhered to the chemotherapy protocol, compared with a 65% response rate achieved in a previous series of children treated with pulsed cyclophosphamide and vincristine with or without doxorubicin. Only six patients, including two of the six children whose treatment did not adhere to protocol, failed to respond, but there were five early deaths from treatment-related complications. Tumor response to OPEC, which was the less toxic of the two regimens, was at least as good as tumor response to OPEC-D. Cisplatin-induced morbidity was clinically significant in only one patient and was avoided in others by careful monitoring of glomerular filtration rate and hearing. Other centers should test the efficacy of OPEC or equivalent regimens in the treatment of advanced neuroblastoma.
Prognostic value of blood glucose in Hodgkin's disease.
Authors: Schilling R F , McKnight B , Crowley J J
Published: February 2017

Subjects with Hodgkin's disease and an initial blood glucose greater than 115 mg/dL had an impressively shorter survival than those with a glucose below that level. The same is true if the groups are formed from those having glucose above or below 100. The correlation between glucose and survival persisted after allowing for the survival effects of histology, stage, symptom class, and age.
Synchronous neuroblastoma and von Recklinghausen's disease: a review of the literature.
Authors: Kushner B H , Hajdu S I , Helson L
Published: February 2017

We report an unusual case of progressive disseminated neuroblastoma occurring in a child with a family history and stigmata of von Recklinghausen's disease. A review of the literature confirms the extreme rarity of finding these two neurocristopathies in a single individual and thus undermines the widely held notion of an association--genetic or otherwise--between these two entities. We propose that synchronous neuroblastoma and von Recklinghausen's disease is accounted for by chance alone and therefore represents a randomly occurring phenomenon.
Altered central nervous system pharmacology of methotrexate in childhood leukemia: another sign of meningeal relapse.
Authors: Morse M , Savitch J , Balis F , Miser J , Feusner J , Reaman G , Poplack D , Bleyer A
Published: February 2017

CSF and plasma antifolate concentrations during 257 intravenous (IV) infusions of high-dose methotrexate were measured in 60 children with acute lymphoblastic leukemia. In 49 children who have never had evidence for CNS leukemia, the mean steady-state CSF to plasma methotrexate ratio was 0.013 (SD = 0.01). In contrast, 11 children with overt meningeal leukemia had a 12-fold higher mean ratio of 0.157 (range, 0.013 to 0.844, p less than .01). In the group of patients studied, all of those with a CSF methotrexate concentration greater than 2 SD above the mean either had leukemic cells in the CSF or subsequently developed this condition. In two patients, overt CNS leukemia was preceded by a high CSF:plasma drug ratio at a time when there was no cytologic or clinical evidence for CNS leukemia. As previously observed with intrathecal methotrexate, we conclude that overt meningeal leukemia increases CSF drug concentrations during IV methotrexate therapy. An elevated CSF to plasma ratio may be useful to predict imminent CNS relapse or to verify completeness of response to therapy.
Morphological subclassification of follicular lymphoma: variability of diagnoses among hematopathologists, a collaborative study between the Repository Center and Pathology Panel for Lymphoma Clinical Studies.
Authors: Metter G E , Nathwani B N , Burke J S , Winberg C D , Mann R B , Barcos M , Kjeldsberg C R , Whitcomb C C , Dixon D O , Miller T P
Published: February 2017

A collaborative study between the Repository Center for Lymphoma Clinical Studies and the members of the lymphoma pathology subcommittee of the major cooperative oncology groups was undertaken in an effort to ascertain the reproducibility and the interobserver agreement for the cytologic diagnosis of follicular lymphomas. A group of 105 patients with follicular lymphomas were subclassified by seven hematopathologists according to two methods. In the first method, cases were subclassified according to the Rappaport, Lukes, and Collins, and Working Formulation systems. In these systems, follicular lymphomas are subclassified by estimation of the different cell populations without the actual counting of cells. With this method, great variability in diagnosis was noted. For example: (1) The consensus diagnosis was that of poorly differentiated lymphocytic lymphoma (PDL) in 39 cases, but among the individual pathologists the number of cases thus diagnosed ranged from 24 to 65; (2) In 40 cases, the consensus diagnosis was follicular lymphoma, mixed-cell type; however, all seven pathologists independently agreed on this subtype in only one case; (3) A major disagreement was noted in 39 cases (37%), in which both diagnostic extremes (small cleaved and large noncleaved) were expressed. In the second method, only precise counts of different cells were made, according to a modification of the method recommended by Berard. With this counting method, diagnoses were independently derived based on the counts provided by the seven pathologists for large cleaved, small noncleaved, and large noncleaved cells. The variability in the results was wide also with this second method. For example, the average number of large cells found by each pathologist was ascertained, and the ranges were determined. The average range was 28 cells, which was considered high. The same determinations were performed only for large noncleaved cells, and the range was found to be 15 cells, which was also considered high. When the diagnoses derived from counts of only large noncleaved cells were compared with the traditional, more subjective diagnoses, fairly close agreement was obtained. In summary, the great variability in diagnoses of follicular lymphomas among pathologists may be attributed to the difficulties inherent in accurate determination of cell size and of the precise percentages of different cells. Until solutions to these problems are developed, one can subclassify follicular lymphomas according to the Berard method or the estimation method.
Correlation of chromosome abnormalities with patient characteristics, histologic subtype, and induction success in children with acute nonlymphocytic leukemia.
Authors: Woods W G , Nesbit M E , Buckley J , Lampkin B C , McCreadie S , Kim T H , Piomelli S , Kersey J H , Feig S , Bernstein I
Published: February 2017

Cytogenetic analyses of bone marrow cells were performed in 195 children with acute nonlymphocytic leukemia (ANLL) at diagnosis, as part of Childrens Cancer Study Group Study No. 251. Ninety-six patients (49%) exhibited clonal abnormalities, including trisomy 8 in 18 patients, t(8;21) in 11, t(15;17) in seven, loss of a sex chromosome in seven, monosomy 7 in seven, and the Philadelphia chromosome in four. Clonal abnormalities were found significantly more often in younger patients. Furthermore, recurring cytogenetic abnormalities tended to correlate with specific ages. For example, t(8;21) was associated significantly with children over four years of age, while -7 associated with overall loss of genetic material from the long arm of chromosome 7 (7q) and 11q- were associated significantly with younger children. Recurring chromosome abnormalities also correlated with specific ANLL histologic subtypes, such as t(8;21) with acute myelogenous leukemia and t(15;17) with acute promyelocytic leukemia. Presence or absence of cytogenetic abnormalities was compared with the ability of patients to achieve remission. Individuals exhibiting clonal abnormalities in bone marrow cells had an equally likely chance of achieving remission (74%) as those individuals with normal karyotypes (75%). Nonrandom chromosome abnormalities associated with a high induction success rate included +8 with a 94% induction success rate (P = .13) and t(8;21) with a 91% success rate (P = .46). Patients exhibiting the -7 abnormality associated with overall loss of 7q had a significantly less successful induction outcome, with only 28% achieving remission (P = .02); three of seven patients with t(15;17) died during induction therapy.
Improved survival following combined radiation therapy and chemotherapy for unfavorable prognosis stage I-II non-Hodgkin's lymphomas.
Authors: Mauch P , Leonard R , Skarin A , Rosenthal D , Come S , Chaffey J , Hellman S , Canellos G
Published: February 2017

A retrospective analysis of 144 patients with stage I-II non-Hodgkin's lymphoma (NHL) treated between June 1968 and December 1980 was performed. Patients were staged by bone marrow biopsy, chest radiography, blood chemistries, and either bipedal lymphangiography, computerized axial tomography, or surgical exploration of the abdomen. Patients were subclassified by extent of disease; minimal disease was defined as less than 10 cm and involved one or two contiguous sites, while patients with disease exceeding these limitations were considered to have extended stage I-II disease. Treatment consisted of radiation therapy (RT) alone in 74 patients and 70 patients were treated with chemotherapy with or without RT. Combination chemotherapy in patients with diffuse undifferentiated (DU) or diffuse histiocytic (DH) lymphoma resulted in a significantly higher 6-year survival as compared to patients treated with RT alone. For minimal disease DU/DH patients, the 6-year survival with chemotherapy +/- RT was 96% as compared to 61% with RT alone (P = .03). For extended disease DU/DH patients the 6-year survival with chemotherapy +/- RT was 56% as compared with 18% with RT alone (P = .003). This survival advantage from the initial use of chemotherapy was not seen in any of the other histologic subgroups.
Carcinoembryonic antigen: a useful prognostic marker in small-cell lung cancer.
Authors: Sculier J P , Feld R , Evans W K , Shepherd F A , DeBoer G , Malkin D G , Malkin A
Published: February 2017

Plasma carcinoembryonic antigen (CEA) was determined in 180 patients with small-cell lung cancer (SCLC) before treatment. An abnormal level (greater than or equal to 6 ng/mL) was found in 34% of patients tested. Patients with extensive disease (39/83) had a significantly higher frequency of abnormal CEA (P = .001) than those with limited disease (22/97). There was a strong correlation between obtaining an objective response--particularly a complete response (P = .00003)--and the absence of an elevated CEA. Patients with an abnormal CEA also had a shorter survival time (P = .0007) and the difference remained statistically significant after logrank adjustment for extent of disease and ECOG (Eastern Cooperative Oncology Group) performance status. There was also a negative correlation between survival time and the quantitative level of CEA. In this series, only the group of patients with normal initial CEA levels included all survivors beyond 2.5 years. We conclude that CEA is a useful prognostic factor in SCLC.
Single agent vincristine by infusion in refractory multiple myeloma.
Authors: Jackson D V , Case L D , Pope E K , White D R , Spurr C L , Richards F , Stuart J J , Muss H B , Cooper M R , Black W R
Published: February 2017

A phase 2 trial of vincristine infusion was conducted in a group of 21 patients with refractory multiple myeloma. Patients were generally heavily pretreated with radiotherapy and chemotherapy. Vincristine was given intravenously (IV) as a 0.5 mg bolus and followed immediately by infusion of 0.25 to 0.50 mg/m2/d for 5 days. Courses were repeated every 3 weeks in the absence of disease progression or prohibitive toxicity. Objective responses (partial) were noted in two patients (10%), both of whom were administered 0.5 mg/m2/d infusions. Response durations were brief (2.2 and 1.2 months). Toxicity consisted of neurotoxicity and myelosuppression. In addition to the occurrence of paresthesias and myalgias, ileus (two cases) and moderately severe loss of motor function (two cases) were observed. The mean lowest WBC count following treatment was 2.67 X 10(3)/microL v 3.96 X 10(3)/microL pretreatment (P = .008). The mean lowest platelet count was 75.0 X 10(3)/microL v 106.8 X 10(3)/microL pretreatment (P = .008). Vincristine infusion appears to have limited activity in the treatment of refractory multiple myeloma. Additionally, response durations were short lived and toxicity, both neurologic and hematologic, was appreciable.
Therapy for metastatic colorectal cancer with hepatic artery infusion chemotherapy using a subcutaneous implanted pump.
Authors: Shepard K V , Levin B , Karl R C , Faintuch J , DuBrow R A , Hagle M , Cooper R M , Beschorner J , Stablein D
Published: February 2017

Sixty-two patients with metastatic colorectal carcinoma involving the liver were treated by hepatic intra-arterial chemotherapy using an implantable infusion pump. The 53 patients with metastases confined to the liver had a median survival (MS) of 17 months and an objective response rate of 32%. Four patients (8%) demonstrated a complete response (CR), with normal abdominal computed tomography (CT) scan results and plasma carcinoembryonic antigen (CEA) levels, and 13 patients (25%) demonstrated a partial response (PR), with at least a 50% decrease in the liver lesions by CT scan and at least a 50% decrease in CEA levels. Thirty patients (57%) had stable disease (S), and six patients (11%) had no response (NR). Nine patients with extrahepatic tumor plus hepatic metastases had an MS of only 4.9 months. None of these patients had an objective response, and only four patients had S. Quality of response was clearly associated with longevity. Forty patients treated with floxuridine (FUDR) and mitomycin (M) (F + M) showed a 20% objective response rate, while the 13 patients treated with FUDR and dichloromethotrexate (DCMTX) (F + D) attained a 69% objective response rate. Although F + D treatment appears to be superior, there may have been selection biases that make such an observation only preliminary. Twenty-six (49%) of the 53 patients developed hepatitis during infusion chemotherapy, which resolved after temporary cessation of the chemotherapy. Of the 17 patients with CR or PR, 12 patients (71%) had hepatitis, whereas only 14 (39%) of the 36 patients with S or NR had hepatitis. Eleven patients had evidence of peptic ulceration by endoscopic examination during the infusion chemotherapy. All the ulcers healed after chemotherapy was discontinued.
Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia.
Authors: Rivera G K , Evans W E , Kalwinsky D K , Mirro J , Ochs J , Dow L W , Abromowitch M , Pui C H , Dahl G V , Look A T
Published: February 2017

In early 1984, we treated 13 consecutive patients with acute lymphoblastic leukemia (ALL) using an induction regimen of rapidly rotated combinations of prednisone, vincristine, asparaginase, teniposide (VM-26), cytosine arabinoside, and high-dose methotrexate (MTX) followed by leucovorin rescue. The intent of this clinical trial, designated Total Therapy Study XI, is to test the hypothesis that greater initial leukemia cell kill will decrease opportunities for the development of drug-resistant mutants, with resultant improvement in the length of disease-free survival. Five patients experienced life-threatening gastrointestinal toxicity within three weeks of the start of treatment. One died. Three other patients had severe abdominal pain, abdominal distention, diarrhea, and weight loss, but not gastrointestinal bleeding. In the remaining five patients, toxicity was rapidly reversible, and each child was able to complete the planned course of chemotherapy. The study was then amended to switch high-dose MTX from the induction phase to the consolidation phase, allowing at least one week for mucosal recovery. Among the next 28 patients who were treated, none showed evidence of severe gastrointestinal toxicity. Patients now receive high-dose MTX alone as consolidation therapy and are tolerating it adequately. Drug timing should be examined critically when intensified multiple-agent regimens are being devised for initial treatment of ALL.
Extended versus involved fields irradiation combined with MOPP chemotherapy in early clinical stages of Hodgkin's disease.
Authors: Zittoun R , Audebert A , Hoerni B , Bernadou A , Krulik M , Rojouan J , Eghbali H , Merle-Béral H , Parlier Y , Diebold J
Published: February 2017

From 1976 to 1981, 335 patients with untreated Hodgkin's disease, clinical stages I, II, and IIIA, have been treated by MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy, three to six cycles according to the prognostic factors, combined with radiotherapy. Irradiation was always performed after the first three cycles of chemotherapy, and was randomized between extensive radiotherapy, ie, mantle and paraaortic areas for supradiaphragmatic presentations, and radiotherapy restricted to the involved areas. No significant difference was observed between the two randomized branches for the disease-free survival (86% after six years in the involved field branch v 90% in the extended field branch), and none for the overall survival. Most of the relapses occurred in nonirradiated areas in the first group, and in irradiated areas in the second. Relapses were especially frequent in the IIE stages with pulmonary extension; extranodal relapses occurred with osseous and cutaneous localizations. Two cases of secondary leukemia were observed after three- or six-cycle MOPP plus radiotherapy limited to the involved areas.
Prognostic groups for management of localized Hodgkin's disease.
Authors: Sutcliffe S B , Gospodarowicz M K , Bergsagel D E , Bush R S , Alison R E , Bean H A , Brown T C , Chua T , Clark R M , Curtis J E
Published: February 2017

Two hundred fifty-two patients receiving radical irradiation for clinical stages I and II Hodgkin's disease between 1968 to 1977 had an actuarial ten-year survival rate of 78% and a relapse-free rate of 61%. Sixty-seven patients receiving chemotherapy followed by radiation had a 78% survival rate and a 63% relapse-free rate. Independent prognostic factors for survival and relapse were age, stage, and histology. Disease bulk was predictive only of relapse. Neither site of presentation above or below the diaphragm nor presence of mediastinal involvement was predictive for survival or relapse; however, patients with large mediastinal masses (greater than or equal to 10 cm absolute diameter) had a significantly higher intrathoracic failure rate with conventional mantle irradiation. Analysis of failure, according to age, clinical stage, and histologic type, showed three groups of patients defined according to the risk of relapse with radiation therapy: those with isolated upper cervical stage IA disease (group 1, relapse rate 8%), younger patients with localized stages I and II disease of favorable histologic type (group 2, relapse rate 35%), and older patients with extensive or symptomatic stages I and II disease of less favorable histologic type (group 3, relapse rate 70%). Subsequent analysis of radiation treatment volume indicates that the use of upper abdominal irradiation for patients in group No. 2 could yield results equivalent to those achieved with radiation therapy for surgically staged patients.
Phase I trial of an implanted battery-powered, programmable drug delivery system for continuous doxorubicin administration.
Authors: Vogelzang N J , Ruane M , DeMeester T R
Published: February 2017

A second generation, implantable drug administration device (DAD, Medtronic, Inc, Minneapolis) which contains a 20-mL drug reservoir, a lithium-thionyl-chloride battery, a peristaltic roller pump, a microprocessor circuit, and an acoustic transducer has entered clinical trials. After surgical placement, drug is entered into and removed from the DAD percutaneously through a Silastic "fill port" using a standard gauge needle and syringe. The pump is noninvasively programmed using a hand-held telemetry wand to administer the drug in a continuous infusion, bolus, or bolus-delay mode. Because of the apparent improved therapeutic index of continuous-infusion doxorubicin (CID), a phase I trial of the Medtronic DAD with CID was begun. Thirteen pumps in 13 patients have functioned for a median of 153 days (range, 11 to 395 days) with one pump still functioning. Four pumps ceased function at 170, 278, 331, and 370 days, respectively; there was a catheter-tip clot on one of the pumps that later malfunctioned. All other pumps functioned until the death of the respective patients. In 84 pump refills, without drug extravasation, the median drug delivery error (actual residual volume--calculated residual volume/calculated residual volume X 100%) was 14%. Doxorubicin was compatible with all components of the drug pathway and did not significantly decompose during two weeks in the drug reservoir. The starting dose of CID was 2.0 mg/m2/d and the maximum tolerated dose was 4.1 mg/m2/d (range, 3.5 to 5.5). A median cumulative doxorubicin dose of 244 mg/m2 per patient (range, 10 to 583 mg/m2) has been infused.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of chemotherapeutic agents on chemotaxis and random migration of human leukocytes.
Authors: MacFadden D K , Saito S , Pruzanski W
Published: February 2017

Chemotherapeutic agents (CTAs) used for treatment of neoplastic and other diseases may influence defense mechanisms of the patient, altering various humoral and cellular immunologic functions. Herein we report the influence of 16 CTAs on random migration and chemotaxis of human polymorphonuclear cells (PMNCs), using two methods, under-agarose migration and double-filter Boyden chambers with 51Cr-PMNCs. Random migration was inhibited by vinblastine only (P less than .01). BCNU and daunorubicin inhibited random migration only when used in high concentrations. In under-agarose migration, only BCNU and vinblastine inhibited chemotaxis (P less than .01) in therapeutic concentrations. Inhibition was also observed when higher concentrations of vincristine were tested. In the Boyden method, marked inhibition of chemotaxis (P less than .01) was caused by BCNU, vinblastine, vincristine, daunorubicin, and doxorubicin. Inhibition of chemotaxis could not be reversed by washing the cells after preincubation. CTAs per se did not have chemoattractant activity. This study shows that some chemotherapeutic agents inhibit random and directed migration of human PMNCs. It also supports the evidence that Boyden chamber method may detect chemotactic abnormalities that escape recognition by the under-agarose migration method. Suppression of locomotion of PMNCs should be taken into consideration in patients treated with CTAs.
Risk-benefit relationships in cancer clinical trials: the ECOG experience in non-small-cell lung cancer.
Authors: Simes R J
Published: February 2017

Although there is widespread recognition of the need to critically evaluate risks and benefits for patients participating in clinical trials, the actual implementation can be a difficult task. As an illustration of the analytic difficulties, we reviewed the experience of the Eastern Cooperative Oncology Group (ECOG) in advanced (inoperable) non-small-cell lung cancer over the past ten years (1973 to 1983). Of 2,714 ECOG patients analyzed, 15% showed objective tumor response. Median survival of all patients was 4.2 months, with approximately one half of patient's survival spent on protocol treatment. Thirty-nine percent of patients experienced at least one episode of severe or worse toxicity from therapy. Chemotherapy impact on this disease was assessed by examining trends in patient outcomes over the decade studied and by comparisons with patients receiving no treatment from earlier Veterans Administration Lung Protocols. Introducing more intensive chemotherapy regimens over this period appears to have resulted in some improvement in survival and response to therapy, but at the expense of greater toxicity. Despite modest survival gains achieved by these evolving trials, the community benefit from such trials seems clear, both in identifying ineffective therapies (and avoiding their general use) and as an important step in developing effective regimens. However, the decision for an individual patient to participate in a trial may involve difficult trade-offs between risk and benefit. This study suggests the need to identify subgroups of patients unlikely to benefit from trial participation and stresses the importance of incorporating patient preferences in the final decision. Some of the problems in patient communication are discussed.
Prognosis for Wilms' tumor patients with nonmetastatic disease at diagnosis--results of the second National Wilms' Tumor Study.
Authors: Breslow N , Churchill G , Beckwith J B , Fernbach D J , Otherson H B , Tefft M , D'Angio G J
Published: February 2017

Multivariate statistical methods were used to study prognosis for 632 patients entered on the second National Wilms' Tumor Study who had nonmetastatic, unilateral disease at diagnosis. Separate analyses were conducted for each of four endpoints: abdominal recurrence, distant metastasis, relapse without regard to site, and death. The two most important predictors for metastasis and general relapse were an unfavorable (anaplastic or sarcomatous) histology and the presence of microscopically confirmed disease in the regional lymph nodes. Operative spillage of tumor increased the rates of abdominal recurrence and death, even after accounting for histology and lymph node effects. The presence of a tumor thrombus in the renal vein or IVC increased the risk of metastasis, and intrarenal vascular invasion was associated with general relapse after accounting for histology, lymph nodes, and spillage. However, these latter associations were weaker, and some uncertainty remains regarding the true prognostic import of such findings due to a high degree of collinearity among variables. By contrast to the results of a similar data analysis for the first National Wilms' Tumor Study, specimen weight had no bearing on outcome, and the effects of age at diagnosis were entirely explained by the association of age with other more critical factors.
Homoharringtonine: an effective new drug for remission induction in refractory nonlymphoblastic leukemia.
Authors: Warrell R P , Coonley C J , Gee T S
Published: February 2017

Homoharringtonine (HHT) is a new plant alkaloid originally isolated in the People's Republic of China. Preliminary studies have suggested antitumor activity in several neoplastic diseases. We treated 49 patients with relapsed or resistant acute leukemia with escalating doses of homoharringtonine administered by continuous infusion. Three dose levels were examined: 5 mg/m2 for seven days, 7 mg/m2 for seven days, and 5 mg/m2 for nine days. Of 28 patients with acute nonlymphoblastic leukemia who received cumulative doses of 45 to 49 mg/m2, seven patients (25%) achieved complete remission. Four of these remissions occurred in a subset of ten patients previously resistant to two or more induction attempts with conventional chemotherapy. There were no remissions in three patients with secondary leukemia or in seven patients with acute lymphoblastic leukemia. Reversible hypotension, fluid retention, diarrhea, and tumor lysis syndrome were the major toxic effects of this treatment. Our results indicate that homoharringtonine is an effective new drug for the treatment of acute nonlymphoblastic leukemia and that this drug does not share cross-resistance with conventional antileukemic agents. The recommended dose is 5 mg/m2/d administered by continuous infusion for nine days.
The significance of the residual mediastinal mass in treated Hodgkin's disease.
Authors: Jochelson M , Mauch P , Balikian J , Rosenthal D , Canellos G
Published: February 2017

The chest roentgenograms of 65 patients treated for Hodgkin's disease with mediastinal adenopathy were analyzed retrospectively to determine the incidence and significance of residual mediastinal abnormality after treatment. All patients were treated with radiation therapy, and 36 patients received additional chemotherapy. On completion of treatment, 57 (88%) of the 65 patients had some residual mediastinal abnormality. These were either minimal changes in the mediastinal shadow in 30 patients or a widening greater than 6 cm in 27 patients. In the latter group, 11 (40%) of 27 patients continued to have residual mediastinal widening one year after completion of therapy. These patients did not have a higher incidence of recurrence. Long-term follow-up (median, 48 months) revealed continued abnormalities in 24 (40%) of the original 57 patients. Mediastinal abnormalities are common at the end of radiation or combined modality therapy for Hodgkin's disease and do not by themselves indicate persistent active disease or an increased risk for relapse. We strongly recommend that additional chemotherapy or higher radiation doses beyond the initially planned course not be used for residual mediastinal widening.
Renal involvement in diffuse aggressive lymphomas: results of treatment with combination chemotherapy.
Authors: Geffen D B , Fisher R I , Longo D L , Young R C , DeVita V T
Published: February 2017

Nine (5.1%) of 175 patients with advanced disseminated diffuse aggressive non-Hodgkin's lymphoma presented with renal involvement and were initially treated with combination chemotherapy alone. These patients were classified as having renal involvement based on histologic and radiographic criteria. Five of the nine patients presented with a serum creatinine level greater than 2.5 mg/dL. Four patients achieved a complete remission of all systemic disease. Eight patients had complete resolution of renal involvement. Two patients later had recurrent renal disease associated with other sites of recurrence. All five patients who presented with an elevated serum creatinine level recovered normal renal function; in fact, four patients had normal renal function by the end of the first cycle of therapy. No patient required hemodialysis. Only one patient remains alive and free of disease at 55 months; five patients have died with disseminated disease; two patients have died without evidence of disease; and one patient was lost to follow-up while in remission. Initial local control of renal involvement including normalization of renal function in diffuse aggressive lymphoma can be rapidly achieved by combination chemotherapy alone.
Phase II study of recombinant alpha-2 interferon in resistant multiple myeloma.
Authors: Costanzi J J , Cooper M R , Scarffe J H , Ozer H , Grubbs S S , Ferraresi R W , Pollard R B , Spiegel R J
Published: February 2017

A multicenter phase II study of INTRON, recombinant alpha-2 interferon (Schering Corp, Kenilworth, NJ), in patients with relapsing or refractory myeloma was initiated. Patients received either intravenous therapy for two weeks followed by subcutaneous therapy or subcutaneous dosing from initiation of treatment. Of 38 evaluable patients, 19 were refractory and 19 had relapsed at entry. Twenty-five of 38 had received prior treatment with multiple drugs. Responses were seen among 2/19 refractory patients and 5/19 relapsing patients. Three of seven responders continue to respond for more than one year while receiving maintenance therapy. Most patients experienced improvement in bone pain, and one patient, with a complete response, had healing of bone lesions. Survival curves show a statistically significant improvement in survival for responders v nonresponders. INTRON was well-tolerated with only four patients discontinuing treatment due to adverse effects. Thirty-two percent of patients had hematologic toxicity requiring dose adjustment; however, there was no evidence of cumulative hematologic toxicity. No patients developed serum neutralizing factors to interferon. Additional trials are warranted to study the activity of INTRON in previously untreated patients.
Inhibition of phorbol ester--induced human epidermal ornithine decarboxylase activity by oral compounds: a possible role in human chemoprevention studies.
Authors: Loprinzi C L , Verma A K , Boutwell R K , Carbone P P
Published: February 2017

Extensive animal data have suggested that, in some systems, the induction of ornithine decarboxylase (ODC) is an essential, although not sufficient, aspect of tumor promotion and that compounds that inhibit ODC can inhibit tumor formation. Using fasting human volunteers, we report that human epidermal and dermal ODC are consistently induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in a manner similar to that seen in mouse skin. There is a marked intersubject variation in TPA-induced epidermal ODC activity levels. Orally administered compounds significantly inhibited TPA-caused human epidermal ODC induction. These data may be useful in the further development of drugs, doses, and dose schedules for use in human cancer chemoprevention studies.
Iodine 125 suture implants in the management of advanced tumors in the neck attached to the carotid artery.
Authors: Paryani S B , Goffinet D R , Fee W E , Goode R L , Levine P , Hopp M L
Published: February 2017

Between 1975 and 1982, 38 patients with locally advanced head and neck cancer attached to the carotid artery underwent surgical excision followed by iodine 125 vicryl suture implant in the neck. Most patients had neck masses that were greater than 6 cm and stage IV disease without clinically evident distant metastases. Twelve patients had received no previous therapy while 26 underwent an implant for recurrent disease. The local control rate in the implant volume was 79%. The local and regional control rate in all head and neck sites was 53%. The mean survival was 11 months. The overall complication rate was 26%. There was no significant correlation of local control or complications with the minimum total dose, volume implanted, individual 125I seed strength, or total seed strength. In patients with large masses attached to the carotid artery, surgical resection followed by a 125I implant for residual disease is a viable alternative to resection of the carotid artery.
A controlled evaluation of combined 5-fluorouracil, doxorubicin, and mitomycin C (FAM) for the treatment of advanced non-small-cell lung cancer.
Authors: Krook J E , Jett J R , Fleming T R , Dalton R J , Marschke R F , Cullinan S A , Windschitl H E , Everson L K , Brunk F S , Laurie J A
Published: February 2017

One hundred eighty-six patients with advanced non-small-cell lung cancer were randomly assigned to treatment with combined 5-fluorouracil, doxorubicin, and mitomycin C (FAM) or combined methotrexate, doxorubicin, cyclophosphamide, and lomustine (MACC). Respective objective regression rates were comparable at 20% and 16%. Distribution of intervals to progression (overall median, 2.8 months) and survival times (overall median, 5.0 months) were essentially identical between the two regimens. The comparability of therapeutic effect was also evident within the subset of 81 patients who had adenocarcinoma cell type, although MACC showed a small advantage in survival after covariate analysis. In large-cell carcinoma, MACC showed a higher regression rate than that of FAM as well as a small advantage in survival. In squamous-cell carcinoma, however, FAM was superior to MACC in regression rates (32% v 4%) and also provided somewhat longer survival. With regard to toxicity, MACC produced a higher incidence of nausea and vomiting, whereas FAM produced more frequent and severe thrombocytopenia. From an overall standpoint, the therapeutic accomplishments of both regimens were disappointing. Our study does, however, provide additional evidence that mitomycin C-containing regimens may be selectively effective for squamous-cell carcinoma of the lung.
Activation of monocyte-mediated tumoricidal activity in patients with acquired immunodeficiency syndrome.
Authors: Kleinerman E S , Ceccorulli L M , Zwelling L A , Twilley T , Herberman R B , Jacob J , Gelmann E P
Published: February 2017

The purpose of these studies was to determine whether peripheral blood monocytes from acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma could be activated to lyse human tumor target cells in vitro. Monocytes were isolated and incubated for 24 hours in vitro with either medium (control), a crude mitogen-induced lymphokine preparation (MAF), or endotoxin before the addition of [125I]IUdR-labeled A375 melanoma target cells. Cytolysis was determined 72 hours later. Twelve (100%) of 12 patients tested had monocyte-mediated cytotoxicity values that were comparable to those of normal individuals. Recombinant human gamma interferon (IFN gamma) activated both normal and AIDS monocyte-mediated tumoricidal function only when combined with lypopolysaccharide (LPS). In addition, mononuclear cells from ten AIDS patients were also tested for their ability to secrete MAF and IFN gamma in response to a mitogenic stimulus. Lymphokines generated from all ten patients contained substantial amounts of IFN gamma (100 to 2,500 U/mL); however, three of these ten lymphokine preparations failed to activate normal monocytes to lyse tumor cells. These results suggest that monocyte-mediated tumoricidal function of AIDS patients is intact and thus suggest new approaches for the therapy of AIDS.
A pilot study of adjuvant therapy in patients with cervical cancer at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy.
Authors: Wertheim M S , Hakes T B , Daghestani A N , Nori D , Smith D H , Lewis J L
Published: February 2017

The prognosis after surgical therapy (radical hysterectomy and pelvic lymphadenectomy) of stages IB and IIA carcinoma of the cervix is affected by several histopathologic findings within the resected specimen. Patients at high risk of recurrence include those with involved pelvic lymph nodes, lymphatic or vascular invasion in the cervix, tumor size greater than 4 cm, grade 3 lesions, adenosquamous histology, parametrial invasion, and evidence of locally metastatic (noncontiguous) disease. We report the results of adjuvant chemotherapy (cisplatin and bleomycin) and pelvic radiotherapy in 32 patients with cervix cancer deemed to be at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy. The continuous disease-free survival rate for the 32 evaluable patients in 84% at a mean and median follow-up time of 28 months. Three patients are dead of disease and two patients are alive after treatment of local recurrences giving a survival rate of 91%. The two patients who are alive after disease recurrence demonstrated only locally recurrent disease while the three patients who have died with recurrent disease relapsed both locally and systemically. Complications of this treatment program were not significantly greater than those observed in prior studies using the combination of surgery and adjuvant radiotherapy without chemotherapy. When compared with the results from historical controls in a large series of similar patients at the same institution, the results in this pilot study are encouraging and would seem to justify a randomized prospective clinical trial.
Curative testis cancer therapy: psychosocial sequelae.
Authors: Rieker P P , Edbril S D , Garnick M B
Published: February 2017

We examined the long-term impact of advanced testis cancer and its curative therapies on emotional states and outlook on life, employment, intimate relationships, and sexual function. The sample consisted of 74 nonseminomatous and seminomatous tumor patients who had completed treatment two to ten years ago. The majority of men felt that surviving the debilitating treatment(s) was both an accomplishment and worthwhile trade-off. Neither the rate of unemployment (7%) nor divorce (10%) was remarkable. The most critical outcome was in the area of sexual functioning. One fourth to one half of the men reported some type of sexual impairment. Multiple regression results indicate that ejaculatory dysfunction, a side effect of the retroperitoneal lymph node dissection, is significantly associated with distress about both infertility and sexual impairment. Men with sexual impairment report more psychological symptoms, strained intimate relationships, and negative changes in other areas of life functioning. These data, while not definitive, suggest that there are delayed effects and that the subgroup of men, who are least likely to disclose these problems to physicians, are at greater risk for the deleterious outcomes.
Avoidance of gastroduodenal toxicity in patients receiving hepatic arterial 5-fluoro-2'-deoxyuridine.
Authors: Hohn D C , Stagg R J , Price D C , Lewis B J
Published: February 2017

Gastroduodenal inflammation and ulceration have been frequently observed in patients receiving continuous hepatic arterial infusions of 5-fluoro-2'-deoxyuridine (FUDR) for liver malignancy. Thirty-five patients with metastatic colon cancer received hepatic arterial FUDR administered with implanted infusion pumps. At surgery, particular care was taken to identify and divide those vessels arising from the hepatic arteries distal to the point of cannulation that supplied the superior border of the distal stomach and proximal duodenum. None of the patients developed signs or symptoms of gastritis or ulcer attributable to chemotherapy. We contend that gastritis and ulcer in patients receiving hepatic arterial FUDR are due to misperfusion of drug into the upper gastrointestinal tract and that these complications can be largely avoided by use of appropriate surgical techniques.