bluuebunny/crossref_metadata_2025 huggingface dataset:
MOPP/ABV hybrid program: combination chemotherapy based on early introduction of seven effective drugs for advanced Hodgkin's disease.
Authors: Klimo P , Connors J M
Published: February 2017

Seventy patients with advanced Hodgkin's disease, 54 with new disease, and 16 in first relapse after initial radiotherapy, have been treated with a seven-drug, 8-month program: MOPP (nitrogen mustard, vincristine, procarbazine, prednisone)/ABV (Adriamycin [Adria Laboratories of Canada, Mississauga, Ontario], bleomycin, vinblastine) hybrid. A single involved field of radiotherapy was given to selected partial responders after 6 months of chemotherapy. Forty-six of the 52 (88%) evaluable new-disease patients and 14 of the 16 (87%) evaluable patients with relapsing disease reached a complete response. The actuarial overall survival at 49 months for the patients with new disease was 90% (median follow-up from diagnosis was 27 months). For the patients with relapsing disease, the actuarial survival at 54 months was 79% (median follow-up from diagnosis was 27 months). The actuarial relapse-free survival at 41 months for complete responders was 93% for patients with new disease (median follow-up after treatment was 20 months) and 80% for those with relapsing disease (median follow-up after treatment was 27 months). Toxicity was moderate, with two treatment-related deaths and eight episodes of serious infection. These results compare favorably with the best results reported in the literature. Furthermore, they were achieved with a moderate level of toxicity, high drug delivery rates, and a relatively short duration of treatment. The efficacy and toxicity data of the MOPP/ABV hybrid program will now be evaluated in a prospectively randomized multicenter study.
Pathologic Stages IA and IIA Hodgkin's Disease
Authors: Hellman Samuel
Published: February 2017

In the editorial by Samuel Hellman "Pathologic Stages IA and IIA Hodgkin's Disease: Results of Treatment With Radiotherapy Alone, 1968–1980" (Journal of Clinical Oncology 3:749–750, 1985), an error was made that altered the meaning of a sentence. The correct sentence appears below.

As long as such change is the case, there is justification for exposing the patient to the morbidity and, on rare occasions, the mortality of this procedure.
Orchiectomy alone in clinical stage I nonseminomatous testis cancer: a critical appraisal.
Authors: Pizzocaro G , Zanoni F , Milani A , Salvioni R , Piva L , Pilotti S , Bombardieri E , Tesoro-Tess J D , Musumeci R
Published: February 2017

Sixty-two consecutive patients with clinical stage I nonseminomatous testicular cancer were entered into a prospective study to receive no treatment after orchiectomy until clinical evidence of recurrent disease. Of 59 evaluable cases, 41 (69.5%) remained continuously disease free for a median duration of 30 months (range, 18 to 46 months), and evidence of metastatic disease developed in 18 patients (30.5%) from 2 to 36 months after orchiectomy. The median disease-free interval for relapsing patients was 6 months. Retroperitoneal metastases developed in ten patients; seven patients had pulmonary metastases, and one patient had progressive elevation of the serum alpha-fetoprotein level. Relapses were significantly more frequent in patients with either embryonal carcinoma, infiltrating testicular cancer (pT greater than 1), peritumoral vascular invasion, or in those who underwent transscrotal biopsy. One patient with relapse refused salvage therapy and died. The remaining 17 patients have been rendered disease free with cisplatin combination chemotherapy and/or surgery. However, two patients showed further recurrence, with one in the lung and the other one also in the retroperitoneal nodes. In our opinion, surveillance following orchiectomy will provide useful information in clinical stage I nonseminomatous testicular cancer, but it is a difficult study. For the time being, it should be restricted to specialized centers only. In the meanwhile, retroperitoneal lymphadenectomy remains the standard treatment.
Prognostic factors and staging in multiple myeloma: a reappraisal.
Authors: Bataille R , Durie B G , Grenier J , Sany J
Published: February 2017

To assess the important factors in the prognosis and staging of multiple myeloma (MM), we have correlated the presenting clinical features of 147 previously untreated patients with MM with the survival duration using multiple regression analyses. We have included the three major available myeloma-staging systems (MSS), ie, Durie-Salmon (DS), Medical Research Council (MRC), and Merlini-Waldenström-Jayakar (MWJ), plus two new variables related to disease activity: the serum beta 2-microglobulin level (S beta 2M) and the instantaneous rate of bone resorption. Our study confirms the validity of the three MSS in the prediction of survival duration, with a slight but significant advantage for the DS MSS. Among single variables, S beta 2M was the most powerful indicator of prognosis (P less than .0001), serum albumin level being the only variable adding to this significantly (P = .02). Of major interest, S beta 2M alone was a better indicator than MRC and MWJMSS. Finally, S beta 2M and the serum albumin level, variables not included in the three MSS, were better indicators than the classical DS MSS and could be combined simply to give a very powerful system of stratification.
An EBV genome carrying pre-B cell leukemia in a homosexual man with characteristic karyotype and impaired EBV-specific immunity.
Authors: Ernberg I , Björkholm M , Zech L , Sandstedt B , Szigeti R , Andersson J , Henle W , Klein G
Published: February 2017

A Burkitt-like lymphoma/leukemia confined to bone marrow was detected in a human T cell leukemia virus (HTLV)-III/LAV- and Epstein-Barr virus (EBV)-seropositive homosexual man. The tumor cells were EBNA-positive and contained at least 22 EBV genomes per cell. They were totally immunoglobin negative, but showed other markers for B cells detected with monoclonal antibodies. The patient had an impaired cellular immunity to EBV antigens and EBV-infected cells at diagnosis, but these reactions normalized during treatment. Cell clones derived from the bone marrow tumor in vitro also carried EBV and had six different marker chromosomes, including the typical 14q+ chromosome and a t(8 - ;8), which resulted in trisomy for the largest part of 8q. Partial trisomy for 12q was also observed. The patient completed six courses of combination chemotherapy and remains in excellent health after 34 months of follow-up.
Immunochemotherapy in human hepatocellular carcinoma using the streptococcal agent OK-432.
Authors: Imaoka S , Sasaki Y , Ishikawa O , Ouhigashi H , Koyama H , Iwanaga T , Ishiguro S
Published: February 2017

Twenty-one patients with nonresectable hepatocellular carcinoma (HCC) received intraarterial infusion chemotherapy of Adriamycin (Adria Laboratories, Columbus, Ohio) via an indwelling catheter in the hepatic artery. Additional intratumoral injection therapy of OK-432 (50 KE) was administered to ten of these 21 patients. Nine of the ten patients showed a remarkable decrease in lymphocyte count on the first day after therapy. In all of the patients with a decreased lymphocyte count, computed tomograms (CTs) demonstrated evidence of necrosis associated with a rapid decrease in alpha fetoprotein (alpha-FP). Blastogenesis of lymphocytes in peripheral blood induced by phytohemagglutinin (PHA) increased by 3.99 +/- 1.9 (mean +/- SE) times 4 weeks after therapy. On the basis of these results, we concluded that intratumoral injection therapy of OK-432 apparently produced initiation of necrosis in HCC by cell-damaging activity as well as by improvement of cell-mediated immunity.
Soft-tissue and bone sarcoma histopathology peer review: the frequency of disagreement in diagnosis and the need for second pathology opinions. The Southeastern Cancer Study Group experience.
Authors: Presant C A , Russell W O , Alexander R W , Fu Y S
Published: February 2017

Histopathologic peer review of specimens from 216 consecutive patients with soft-tissue or bone sarcomas on Southeastern Cancer Study Group protocols was performed by a panel of three pathologists. Subtype of sarcoma, degree of confidence in diagnosis, and grade were compared with agreement or disagreement in pathologic opinion from the primary member institution v the pathology review panel. The most common soft-tissue sarcoma was leiomyosarcoma, followed by malignant fibrous histiocytoma, fibrosarcoma, liposarcoma, malignant schwannoma, and rhabdomyosarcoma. There was total agreement between the primary pathologist and reviewer in 66% of cases. However, 12 cases (6%) were considered on review to not be sarcomas. In 27% of cases the subtype of sarcoma was felt to be incorrect by reviewers. Discordant diagnoses were more common when the confidence of the pathologist was less and when the tumor was of higher grade. There was no improvement in frequency of agreement in the second half of the study, despite educational workshops. We conclude that histologic peer review is important in sarcoma studies and is essential in many patients with presumed sarcomas.
A randomized study comparing a high and a standard dose of cisplatin in combination with etoposide in the treatment of advanced non-small-cell lung carcinoma.
Authors: Klastersky J , Sculier J P , Ravez P , Libert P , Michel J , Vandermoten G , Rocmans P , Bonduelle Y , Mairesse M , Michiels T
Published: February 2017

We conducted a randomized trial comparing a high (120 mg/m2 day 1) v a standard (60 mg/m2 day 1) dose of cisplatin in combination with etoposide (120 mg/m2 days 3, 5, and 7) in advanced non-small-cell lung carcinoma (NSCLC). Two hundred forty-one patients were evaluable for survival and 207 for response. We obtained a 25% objective response rate in the standard-dose arm and 29% in the high-dose arm; this difference was not statistically significant. There was no significant improvement in the overall survival or survival of responders with the high-dose regimen. However, toxicity (mainly myelosuppression) was significantly increased in the patients receiving the higher dose of cisplatin. An analysis of prognostic factors showed that disease progression, loss of body weight, performance status, and prior therapy were predictive parameters of survival.
High-dose chemotherapy without autologous bone marrow transplantation in melanoma.
Authors: Tchekmedyian N S , Tait N , Van Echo D , Aisner J
Published: February 2017

High-dose chemotherapy with BCNU, melphalan, or both, followed by autologous bone marrow transplantation (ABMT) has been reported to produce response rates in excess of 60% in patients with advanced melanoma. We tested doses of BCNU associated with reversible bone marrow toxicity and acceptable extramedullary toxicity without the use of ABMT in 19 patients with a diagnosis of advanced malignant melanoma. All patients were evaluable for toxicity and 18 were evaluable for response; one patient had a new primary tumor. The patient population had a median age of 44 years (range, 16 to 71) and a median Karnofsky performance status of 80 (range, 50 to 100). Ten were women and nine were men, all had visceral dominant disease, and none had received previous chemotherapy. Our purpose was to test the feasibility of treatment without ABMT, its toxicity and efficacy, and the possibility of administering sequential repeated courses of therapy. Vincristine was added to the regimen to potentially increase efficacy. Treatment consisted of BCNU (750 mg/m2) and vincristine (2 mg days 1 and 8). Six patients who recovered bone marrow function received melphalan (60 mg/m2) and vincristine (2 mg days 1 and 8). Twenty-two percent (95% confidence limits, 3% to 39%) of patients had remissions (all partial) and these were of short duration. Toxicity was substantial with 16% early lethality and 29% incidence of lethal drug-related complications. Two patients (11%) died toxic after a second course of BCNU. Our results suggest that there is no practical role for high-dose BCNU in the treatment of melanoma.
Results of initial lymph node biopsy in homosexual men with generalized lymphadenopathy.
Authors: Levine A M , Meyer P R , Gill P S , Burkes R L , Krailo M , Aguilar S , Parker J W
Published: February 2017

Persistent, generalized lymphadenopathy (PGL) is considered part of the acquired immunodeficiency syndrome (AIDS)-related complex. The clinical course is usually benign, although some patients may evolve to AIDS. Characteristic features on lymph node biopsy have been described. Recently, large series of PGL have been reported in which many study patients have not undergone initial diagnostic biopsy. The value of such biopsy has been questioned. We report the clinical, pathologic, and laboratory findings in six homosexual men initially considered as potential candidates for study of the natural history of PGL. They were excluded by initial lymph node biopsy, which revealed small-cleaved lymphoma in two, focal Kaposi's sarcoma in two, disseminated mycobacterium tuberculosis in one, and histoplasma encapsulatum in one. The clinical and laboratory data from these six patients were compared with those from 34 patients with biopsy-proven PGL; no statistically significant difference in any prebiopsy clinical parameter was found. We conclude that initial lymph node biopsy may reveal changes other than reactive hyperplasia in homosexual men with generalized lymphadenopathy.
Cataracts induced by intermittent Decadron used as an antiemetic.
Authors: Bluming A Z , Zeegen P
Published: February 2017

Recent reports have shown that Decadron (dexamethasone; Merck Sharp & Dohme, West Point, Pa) has a significant antiemetic effect on cisplatin-induced vomiting. Although the development of posterior subcapsular cataracts is a known complication of systemic steroid therapy, it usually occurs after several years of chronic administration. A young diamond dealer developed visual impairment attributed to bilateral posterior subcapsular cataracts following only four courses of intermittent Decadron used as part of a five-drug antiemetic regimen for cisplatin-associated nausea. This report is intended to alert others to the possible development of this serious complication following short-term Decadron therapy.
The pathologic and clinical heterogeneity of lymphocyte-depleted Hodgkin's disease.
Authors: Kant J A , Hubbard S M , Longo D L , Simon R M , DeVita V T , Jaffe E S
Published: February 2017

Patients with Hodgkin's disease of the lymphocyte-depleted subtype (LDHD) have been said to have a poor prognosis. However, reports of this subtype are complicated by the fact that the histologic diagnosis of LDHD is often not straightforward, and its distinction from aggressive non-Hodgkin's lymphomas (NHL) can be difficult. We have reviewed our patients with LDHD at the National Cancer Institute (NCI) in light of an additional decade of experience with neoplastic and non-neoplastic conditions mimicking Hodgkin's disease. Of 198 patients who received MOPP (mechlorethamine, vincristine, procarbazine, prednisone) treatment at the NCI for Hodgkin's disease between 1964 and 1976, 43 (22%) were originally classified as LDHD. The initial diagnostic biopsies from 39 of these patients were reviewed and revealed ten with NHL, nine with LDHD, and 13 with nodular sclerosing Hodgkin's disease of the lymphocyte-depleted subtype (NSLD). The other seven patients had Hodgkin's disease without a lymphocyte-depleted component. The NHL patients were further subclassified as diffuse, large-cell (two cases) and large-cell, immunoblastic (eight cases). The pathologic review was done without knowledge of clinical features which were examined after review in the three major subgroups. Of ten patients with NHL, only three had a complete remission (CR), and median survival was 7 months. Nine of the NHL patients presented with features that are unusual for patients with Hodgkin's disease, such as bulky abdominal disease, epitrochlear lymphade-nopathy, or hypercalcemia. CRs were attained by 67% and 85% of patients in the LDHD and NSLD groups, respectively: median survival had not been reached in either group with a median of 14 years of follow-up. Lymphocyte-depleted Hodgkin's disease, adequately treated, is in our limited group of patients no worse than other histopathologic subtypes of Hodgkin's disease. The erroneous inclusion of patients with high-grade NHLs into this subtype of Hodgkin's disease may be one reason for earlier literature reports of its more aggressive nature. The diagnosis of LDHD should be made cautiously, particularly in patients with clinical features that are unusual for Hodgkin's disease at presentation.
Second neoplasms in patients with Hodgkin's disease following combined modality therapy--the Yale experience.
Authors: Koletsky A J , Bertino J R , Farber L R , Prosnitz L R , Kapp D S , Fischer D , Portlock C S
Published: February 2017

From 1969 to 1982, 183 patients with previously untreated stages IIIB and IV Hodgkin's disease and relapsing Hodgkin's disease after radiation therapy were treated with combination chemotherapy plus low-dose irradiation (CRT). One hundred fifty patients who achieved a complete response (CR) were analyzed for risk of developing a second neoplasm. Median follow-up has been 8.3 years. Actuarial survival of all patients is 74% at 10 years with a relapse-free survival of 68%. An additional 24 patients with stage IIIA disease were also treated with CRT. There were 22 CRs at risk who were analyzed. Median follow-up has been 3+ years with an actuarial survival of 90% at five years and a relapse-free survival of 83%. Second neoplasms have developed in 14 of 172 patients at risk: acute nonlymphocytic leukemia (ANLL; five patients); aggressive histology non-Hodgkin's lymphoma (NHL; three patients); and a variety of solid neoplasms (six patients). Time to second neoplasm diagnosis after initial treatment ranged from 12 to 141 months. Five patients were older than 40 years. At the time of diagnosis of the second malignancy, 11 patients were free of Hodgkin's disease (for 36 to 141 months) and three were receiving therapy for recurrent Hodgkin's disease. The 10-year actuarial risk (%) of developing ANLL was 5.9 +/- 2.8; for NHL, the risk was 3.5 +/- 2.4, and for solid neoplasms, 5.8 +/- 3.0. Our results suggest that combination chemotherapy plus low-dose irradiation does not appear to significantly increase the risk of developing second neoplasms above that already reported for combination chemotherapy when administered as either initial or salvage treatment of Hodgkin's disease.
Detection of neuroblastoma cells in bone marrow using GD2 specific monoclonal antibodies.
Authors: Cheung N K , Von Hoff D D , Strandjord S E , Coccia P F
Published: February 2017

Three murine monoclonal antibodies (Mab) against a cell surface antigen, the disialoganglioside GD2, were investigated for detecting bone marrow metastasis in patients with neuroblastoma (NB) by indirect immunofluorescence (IF). As few as 0.01% NB cells could be detected. No Mab reactivity was found in 60 non-NB marrows. Thirty-five marrows from patients with stage III and stage IV NB at diagnosis were examined during the course of their disease. Tumor involvement was found in 74% by Mab, 55% by the two-layer soft agar clonogenic assay (CA), and 27% by conventional histochemical stains. All marrows containing NB histologically were positive for tumor by Mab; 71% were also positive by CA. Of histologically negative marrows, 63% were Mab positive, the majority (78%) of which were also positive by CA. All Mab nonreactive samples were negative histologically and by CA. We conclude that these antibodies are highly sensitive and specific in detecting NB metastasis in bone marrow.
5-fluorouracil, adriamycin, and mitomycin in the treatment of adenocarcinoma of unknown primary.
Authors: Goldberg R M , Smith F P , Ueno W , Ahlgren J D , Schein P S
Published: February 2017

The combination of 5-fluorouracil (5-FU), doxorubicin, and mitomycin (FAM) is often recommended for empiric management of patients with adenocarcinoma of unknown primary. This recommendation is based on the activity of FAM for adenocarcinomas of specific known sites of origin. A literature search disclosed no reports of the efficacy of FAM in this clinical entity. We report on 45 patients with biopsy-proven adenocarcinoma in whom investigation revealed no primary site and who were treated in a phase II trial with FAM. Of 43 evaluable patients, four achieved a complete tumor response, and nine obtained a partial response for an overall response rate of 30%. The median survival for all patients was greater than 10 months. The median survival for patients whose tumors were unresponsive to FAM was 6 months, and median survival was greater than or equal to 14 months in patients with stable disease or FAM-responsive tumors. A phase III trial comparing no therapy or 5-FU with FAM is warranted. For patients not treated in an investigative setting, FAM compares favorably with reported series using other regimens.
Primary lymphoma of bone in children: analysis of treatment results with adriamycin, prednisone, Oncovin (APO), and local radiation therapy.
Authors: Loeffler J S , Tarbell N J , Kozakewich H , Cassady J R , Weinstein H J
Published: February 2017

Primary lymphoma of bone is an unusual extranodal presentation of pediatric non-Hodgkin's lymphoma (NHL). Treatment with radiotherapy alone has resulted in a disease-free survival rate of approximately 50% in most adult series. Between January 1973 and April 1985, 11 children with biopsy-proven NHL of bone were seen and treated at our institutions. The minimal clinical staging included chest and bone radiographs, a radionuclide bone scan, complete blood cell counts and serum chemistries, and a bone marrow aspirate and biopsy. The age range was 9 to 17 years with a median age of 14 years. Histology included diffuse lymphoblastic lymphoma in four patients and diffuse histiocytic lymphoma in seven. Each patient was treated with the Adriamycin/prednisone/Oncovin (APO) protocol and ten patients received concomitant radiation to the whole bone when possible and a boost to the primary lesion(s). The median tumor dose was 5,000 rad (range, 3,600 to 5,600). The median follow-up was 8 years. There have been no relapses, but two patients have developed second bone tumors 5 and 7 1/2 years after beginning therapy. Each second tumor arose directly in the radiation field. The overall 8-year actuarial survival is 83%. We conclude that APO and local radiation results in excellent overall survival for children with primary NHL of bone. The occurrence of two second bone tumors, however, raises questions regarding dose and/or the role of radiation for this disease.
VP-16 plus ifosfamide plus cisplatin as salvage therapy in refractory germ cell cancer.
Authors: Loehrer P J , Einhorn L H , Williams S D
Published: February 2017

Forty-eight evaluable male patients with germ cell tumors (GCT) failing to be cured with first-line therapy were treated with VP-16 (75 mg/m2), ifosfamide (1.2 g/m2), and cisplatin (20 mg/m2) (VIP), all given daily for 5 consecutive days every 3 weeks. All patients either achieved an unresectable partial remission as their best response to induction chemotherapy (Group A), relapsed from complete remission (CR) less than or equal to 2 months after induction therapy (Group B), or had received cisplatin plus VP-16 as previous salvage therapy (Group C). Nine (19%) had extragonadal GCT, and 37 (77%) had advanced disease. Twenty-three (48%) of the patients had greater than or equal 2 prior treatment regimens. Sixteen of 48 (33%) achieved CR with VIP treatment alone or following surgical excision of residual disease. Six of 22 (27%), three of seven (43%), and seven of 19 (37%) patients from groups A, B, and C, respectively, attained a CR. The median survival time of all patients was 7 months (range 0 to 28+) with seven patients remaining continuously free of disease (four patients greater than 1 year). Myelosuppression was significant with a median WBC nadir of 900/mm2 and platelet nadir of 24,000/mm2. Fourteen (26%) had granulocytopenic fever, and renal insufficiency developed in 15%. VIP combination chemotherapy demonstrates activity in this highly unfavorable population of patients with germ cell tumors. The actual contribution of ifosfamide in this regimen is unclear, but these results compare favorably to our experience with similar patients treated with cisplatin plus VP-16 alone. Further studies with VIP as initial salvage therapy for patients with GCT are planned.
A mastectomy--how so? An etymologic plea.
Authors: MacMillan R W , Olson J E
Published: February 2017

The word mastectomy and its modifiers are used so loosely and have so many meanings in the literature that it is often difficult to determine precisely what procedure the authors are discussing. Simple descriptive terms should be used that would standardize the terminology with respect to operative techniques. The classical term radical mastectomy should be reserved to refer to a complete en bloc resection of the breast with the pectoralis major and minor muscles and the entire axillary contents, with or without a skin graft for wound closure. A total mastectomy should indicate a complete resection of the breast, including the fascia of the pectoralis major muscle. A local excision should be defined as a resection of the primary tumor with margins that are free of disease, with specific margins stated if desired. The axillary lymph node dissection should be defined according to the extent of the axillary contents excised.
Leukemia in Breast Cancer Patients Following Adjuvant Chemotherapy or Postoperative Radiation
Authors: Fisher Bernard , Rockette Howard , Fisher Edwin R. , Wickerham D. Lawrence , Redmond Carol , Brown Ann
Published: February 2017

In the article by Fisher et al in the December 1985 issue (Leukemia in Breast Cancer Patients Following Adjuvant Chemotherapy or Postoperative Radiation: The NSABP Experience, J Clin Oncol 3:1640–1658, 1985), an error was made in the body and notes of Table 1 (page 1642). References made to "cyclophosphamide parvum" should have read "Coryne bacterium parvum."
Pharmacokinetics of dibromodulcitol in humans: a phase I study.
Authors: Kelley S L , Peters W P , Andersen J , Furlong E A , Frei E , Henner W D
Published: February 2017

A combined clinical and pharmacokinetic phase I study of the substituted hexitol dibromodulcitol (DBD), administered as a single oral monthly dose, has been performed. Twenty-three patients with advanced neoplasms received DBD doses ranging from 600 to 1,800 mg/m2 body surface area (BSA). The dose-limiting toxicity was myelosuppression, with both significant granulocytopenia and thrombocytopenia occurring at dose levels of 1,500 to 1,800 mg/m2. The average pharmacokinetic parameters for DBD, calculated on the basis of a one-compartment model with first-order absorption and elimination, include the elimination constant, .005 +/- .002/min; absorption constant, .012 +/- .009/min; and an apparent volume of distribution, 1.03 +/- .4 L/kg. The area under the drug concentration curve (AUC) and the peak drug level (Cmax) were linearly related to the dose administered (P less than .001). The mean AUC was 18.7 +/- 6.1 mmol/L min, and the mean Cmax was 47.1 +/- 16.8 mumol/L when normalized to a DBD dose of 1 gm/m2. The elimination constant was significantly reduced in patients with abnormal hepatic function (P less than .01). The elimination constant was not correlated with renal function. The half-life of DBD in plasma (158 minutes) was considerably shorter than the four-to eight-hour half-life of total radioactivity in plasma measured by previous investigators following the administration of radiolabeled DBD.
Second Neoplasms in Patients With Hodgkin's Disease Following Combined Modality Therapy—The Yale Experience
Authors: Koletsky Alan J. , Bertino Joseph R. , Farber Leonard R. , Prosnitz Leonard R. , Kapp Daniel S. , Fischer Diana , Portlock Carol S.
Published: February 2017

In the article by Koletsky et al "Second Neoplasms in Patients With Hodgkin's Disease Following Combined Modality Therapy—The Yale Experience" (Journal of Clinical Oncology 4:311–317, 1986), an error was made in the footnote on page 311 which described the composition of MVVPP. The corrected footnote appears below.

*MVVPP = nitrogen mustard (0.4 mg/kg on day 1 of cycle); vinblastine (6 mg/m2 on days 22, 29, and 36); vincristine (1.4 mg/m2, 2 mg maximum dose, on days 1, 8, and 15); procarbazine (100 mg/d on days 22 through 42); prednisone (40 mg/m2 on days 1 through 15 for cycles 1, 3, and 5 only).
Phase I-II study of recombinant alpha-2 interferon against advanced leukemia and lymphoma in children.
Authors: Ochs J , Abromowitch M , Rudnick S , Murphy S B
Published: February 2017

Alpha-2 interferon, produced in Escherichia coli using recombinant DNA techniques, was administered to 17 children with refractory acute lymphoblastic leukemia (ALL) in relapse, two children with TdT-positive, Philadelphia chromosome-positive chronic myelocytic leukemia (CML) in blast crisis, and one child with B cell (SIg+) non-Hodgkin's lymphoma (NHL) in a second extramedullary relapse. An initial 2-week intravenous (IV) phase of interferon was followed by a 3-month subcutaneous (SC) maintenance phase if patients had an objective response or disease stabilization without significant bleeding or infectious complications. When interferon dosages were escalated from 3 to 100 X 10(6) U/m2 in the first phase of therapy, there was rapid progression of disease in the first four patients treated, prompting a modification of the treatment plan. The last 16 patients enrolled received fixed dosages of interferon (ie, 10, 20, 30, and 50 X 10(6) U/m2 administered to four subjects each). One child with T cell ALL had an 11-month complete remission; the patient with lymphoma had a dramatic but brief response; three others (one CML and two ALL) showed disease stabilization for 3 to 6 months with a definite oncolytic effect in two of the three patients. The remaining 15 patients had progressive disease within 2 months and were removed from the study. Acute toxicity included a flu-like syndrome in all patients, increased serum transaminase levels in five, seizures in three (two cases temporally related to fever and one to a thrombocytopenic subarachnoid hemorrhage), and prolonged activated partial thromboplastin times in seven. This phase I-II trial of recombinant alpha-2 interferon demonstrated definite activity without dose-limiting toxicity.
A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.
Authors: Conte P F , Bruzzone M , Chiara S , Sertoli M R , Daga M G , Rubagotti A , Conio A , Ruvolo M , Rosso R , Santi L
Published: February 2017

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.
Primary or delayed debulking surgery and chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide in stage III-IV epithelial ovarian carcinoma.
Authors: Wils J , Blijham G , Naus A , Belder C , Boschma F , Bron H , Ceelen T , Eekhout A , von Erp J , Geelen P
Published: February 2017

Eighty-eight previously untreated patients with stage III and IV epithelial ovarian carcinoma were treated with primary or delayed (secondary) optimal debulking surgery unless impossible, and combination chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide intravenously (IV) on day 1, every 4 weeks (CAP-I). In patients with no evidence of disease after six cycles of chemotherapy, a second-look laparotomy was performed. A pathologically confirmed complete response (CR) was obtained in 39% of the patients. The median progression-free survival period of all patients was 18 months and the median survival time 24 months. CAP-I is an effective chemotherapy schedule that can be administered with moderate toxicity and appears to enhance the cure rate in advanced ovarian carcinoma. The role of secondary surgery must be further defined.
A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer.
Authors: Buchanan R B , Blamey R W , Durrant K R , Howell A , Paterson A G , Preece P E , Smith D C , Williams C J , Wilson R G
Published: February 2017

We randomized 122 premenopausal women to receive tamoxifen or to undergo a surgical oophorectomy. Of 54 evaluable women treated with tamoxifen, 24% had an objective response, as compared with 21% of 53 women having an oophorectomy. The median duration of response for tamoxifen (20 months) was longer than that for surgical oophorectomy (7 months), but this did not achieve statistical significance (P = .056). Overall median survival was 15 months for 58 patients receiving tamoxifen and 25 months for 53 patients undergoing oophorectomy (P = .18). Toxicity was greater in those undergoing oophorectomy, though both treatments were well tolerated. In those premenopausal women for whom hormonal therapy is indicated, tamoxifen is a suitable alternative to surgical oophorectomy.
Single, sequential, and multiple alkylating agent therapy for multiple myeloma: a CALGB Study.
Authors: Cooper M R , McIntyre O R , Propert K J , Kochwa S , Anderson K , Coleman M , Kyle R A , Prager D , Rafla S , Zimmer B
Published: February 2017

Four intravenous (IV) alkylating agent regimens were tested in 615 previously untreated patients with multiple myeloma. Patients were randomized to receive melphalan, cyclophosphamide, and carmustine in combination (MCBP), sequentially (Seq-MCBP), or in combination with doxorubicin (MCBPA). The fourth group received IV melphalan (MP) as the only alkylating agent. All groups received a tapering dose of prednisone. Toxicity was similar for all regimens although the nadir of cytopenia was reached more quickly for the regime including melphalan only. Response as measured by reduction in myeloma protein or other parameters were similar for the four treatments. Survival was significantly poorer for the group receiving the alkylating agents in sequence. The survival of high tumor cell load patients who were azotemic was better in the groups treated with IV MP or with the combination of IV MCBP. In view of the simplicity and probable cost savings attached to single-agent treatment, a melphalan/prednisone regimen should be considered as initial therapy for all patients with myeloma.
Chemotherapy of drug-resistant ovarian cancer: a Southwest Oncology Group Study.
Authors: Laufman L R , Green J B , Alberts D S , O'Toole R , Hilgers R D , Young D C , Lin F , Rivkin S E
Published: February 2017

We present a final analysis, including pathology review, of a cooperative group study of drug-resistant ovarian cancer. Of 200 patients registered, 112 were eligible and evaluable, with a response rate of 26% and median survival of 7 months. Because these results are poorer than those reported in the preliminary and interim analyses of this study, we scrutinized the 88 excluded patients, most of whom failed to meet our strict pathologic criteria for a diagnosis of ovarian cancer of epithelial type, and who, as a heterogeneous group, fared better than patients who did meet the eligibility criteria. We believe this analysis provides insight into the spectrum of diseases that are frequently called ovarian cancer, but might be more properly labeled abdominal carcinomatosis.
Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy.
Authors: Santoro A , Bonadonna G , Valagussa P , Zucali R , Viviani S , Villani F , Pagnoni A M , Bonfante V , Musumeci R , Crippa F
Published: February 2017

In an attempt to reduce some of the delayed sequelae associated with combined modality therapy in Hodgkin's disease, we randomly tested stages IIB, IIIA, and IIIB MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) v ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). In 232 previously untreated patients, three cycles of either combination preceded and followed extensive irradiation. The complete remission rate was 80.7% following MOPP and 92.4% following ABVD (P less than .02). The 7-year results indicated that ABVD was superior to MOPP in terms of freedom from progression (80.8% v 62.8%; P less than .002), relapse-free survival (87.7% v 77.2%; P = .06), and overall survival (77.4% v 67.9%; P = .03). Moreover, the comparative iatrogenic morbidity showed that irreversible gonadal dysfunction as well as acute leukemia occurred only in patients subjected to MOPP, while cardiopulmonary studies failed to document significant laboratory differences between the two treatment groups. Present findings indicate that ABVD followed by extensive irradiation represents a valid therapeutic alternative to the widely used alkylating agent-containing regimens plus radiotherapy.
Intra-arterial cisplatin and FUDR in advanced malignancies confined to the head and neck.
Authors: Forastiere A A , Baker S R , Wheeler R , Medvec B R
Published: February 2017

Twenty-seven patients with advanced malignancies confined to the head and neck region were treated with intra-arterial (IA) cisplatin and 5-fluorodeoxyuridine (FUDR) using implantable pumps or injection ports. Tumor histologies were: 16 squamous cell, one mucoepidermoid, one adenocarcinoma, one neuroendocrine, four adenoid cystic, two acinic cell, one fibrosarcoma, and one melanoma. All primaries originated from tissues in the head and neck area. Nineteen patients had received prior treatment, including chemotherapy in 13; eight were newly diagnosed. Responses in 26 evaluable patients were two complete (CR), ten partial (PR), six minor (MR), and eight progressions. The median duration of response was 5 months, with a range of 2 to 11 months. Sites of progression were within the infused volume in 13 patients and to uninfused local-regional or distant sites in eight. The response rate in the subset of 15 patients with squamous cell head and neck cancer was 47%. Toxicity in the 26 patients included stomatitis in 88%, nausea and vomiting in 64%, myelosuppression in 15%, and grade 1 nephrotoxicity in 1%. A regional advantage for IA cisplatin and FUDR can be calculated based on total body clearance rates (CLTB) for these agents and estimates of external carotid artery (ECA) blood flow. However, frequent progression of disease outside the infused volume to regional and distant sites limits the usefulness of this approach in recurrent disease patients.
Major complications and causes of death in patients treated for Hodgkin's disease.
Authors: van Rijswijk R E , Verbeek J , Haanen C , Dekker A W , van Daal W A , van Peperzeel H A
Published: February 2017

A total of 340 patients with Hodgkin's disease were evaluated for the occurrence of intercurrent fatalities after treatment with radiotherapy, chemotherapy, combined modality therapy, and salvage chemotherapy. Mean follow-up time was 76.6 months. Causes of death were compared with the expected risk, calculated from mortality statistics of the Netherlands' population. Sixty-seven patients died of progressive Hodgkin's disease, whereas 37 patients died of causes unrelated to advanced disease. Patients showed an increased risk of dying of leukemia and solid tumors (P less than .001), whereas the risk of dying of cardiovascular complications was not increased. The 10-year actuarial risk of dying of leukemia varied between 0% for patients treated with radiotherapy only and 5.7% for those needing salvage chemotherapy. The 10-year risk of dying of solid tumors was 0% for patients treated with chemotherapy and 6.5% for those receiving radiotherapy. Treatment-related fatalities were highest after combined modality therapy (P less than .025); the corresponding 10-year risk was 6.1%. Compared with younger ones, patients greater than or equal to 40 years had an increased risk of dying of causes unrelated to progressive Hodgkin's diseases. The actuarial risk of developing intercurrent fatalities at 10 years was 4.9% in patients less than 40 years, and 34.7% in those greater than or equal to 40 years (P less than .001). Compared with population based statistics, patients successfully treated for Hodgkin's disease still showed an increased risk of dying (P less than .001). Treatment modality, stage, and histologic subtype were not predictors of intercurrent death.
Combined treatment with chemotherapy and neutron irradiation for limited non-small-cell lung cancer: a Southwest Oncology Group Study.
Authors: Livingston R B , Griffin B R , Higano C S , Laramore G E , Rivkin S E , Goldberg R S , Schulman S F
Published: February 2017

Seventy-three patients with regional, inoperable non-small-cell lung cancer received treatment with initial chemotherapy for two cycles (vinblastine-mitomycin followed in 3 weeks by vinblastine-cisplatin), with planned subsequent neutron irradiation to the primary site and concurrent, elective whole-brain irradiation using photons, followed by two more cycles of identical chemotherapy. Histology was reported as adenocarcinoma or large cell in 75%, and 60% had Radiation Therapy Oncology Group (RTOG) stage 3 disease; the remainder had stage 4. The response rate to chemotherapy induction was 51%. There were 58 patients in a second phase of the study who were potentially eligible for treatment with a medically dedicated cyclotron having more favorable characteristics with regard to treatment planning and dose delivery (neutrons "B"). The overall response rate in this group was 79%. Chemotherapy toxicity included four fatalities (5%), with three related to mitomycin C induced bilateral pneumonitis, and an additional five patients (7%) with life-threatening events that required hospitalization. Two fatalities were attributed to combined effects of chemotherapy and radiation, and six more to chest radiation therapy, for an overall treatment-related death incidence of 12 of 73 (16%). Four of the six deaths related to chest irradiation occurred after treatment with a "physics-based" neutron generator (neutrons "A"). Among the 45 who received neutrons in the B group, two (4%) had radiation-related deaths, and another four (10%) had clinically evident radiation pneumonitis. Pretreatment performance status (PS) and response to chemotherapy, but not RTOG stage or weight loss, were significantly associated with survival. Among patients who actually received chest irradiation, only initial response to chemotherapy remained as a significant predictor of survival in univariate analysis, with a median survival of 20 months in responders v 9 months in chemotherapy nonresponders. The patterns of first relapse observed in B group patients revealed that 28% were distant, while 64% were locoregional. This represents a reversal of the usual pattern in studies of chest irradiation alone. It probably reflects elimination of brain relapse by the use of elective whole-brain irradiation, impact of systemic chemotherapy on micrometastases elsewhere, and conservative treatment volumes employed for the chest irradiation in an attempt to minimize its toxicity. Further exploration of combined modality therapy is indicated for regional non-small-cell disease, with a real potential for survival impact if the therapeutic index can be improved.
Detection of estrogen receptor in bone marrow from patients with metastatic breast cancer.
Authors: Berger U , Mansi J L , Wilson P , Coombes R C
Published: February 2017

We devised a method of detecting estrogen receptors (ER) in bone marrow metastases from patients with breast cancer. The method involves a sequential double-staining immunocytochemical technique, with a monoclonal antibody to ER and a polyclonal antibody recognizing epithelial membrane antigen to confirm the epithelial nature of suspected tumor cells. Twenty-seven patients were assessed: ten were found to have ER-positive tumor cells in the bone marrow; ten had ER-negative cells; and the remaining seven patients had no tumor cells in the bone marrow smears. Of the ten patients with ER-positive cells, eight (80%) either had a response to endocrine therapy, implying that they possess ER-positive breast cancers, or had ER-positive primary tumors as determined by the dextran-coated charcoal biochemical assay (DCC). Of the ten patients with ER-negative cells in the bone marrow, eight failed to respond to endocrine therapy. This technique therefore provides a means of predicting which patients will respond to endocrine therapy, and is particularly important in those patients whose ER status is unknown.