bluuebunny/crossref_metadata_2025 huggingface dataset:
The contribution of salvage surgery to the management of childhood osteosarcoma.
Authors: Pastorino U , Gasparini M , Tavecchio L , Azzarelli A , Mapelli S , Zucchi V , Morandi F , Bellani F F , Valente M , Ravasi G
Published: February 2017

Between January 1970 and December 1988, 174 consecutive patients under the age of 20 years with curatively resected primary osteosarcoma were treated at our institute; 72 in the years of 1970 to 1981 and 102 in the years 1982 to 1988. In the latter period, adjuvant chemotherapy was replaced by neoadjuvant programs, and new criteria were adopted for the management of lung metastases, consisting in early bilateral surgical staging and lung resection through median sternotomy for all patients with purely intrathoracic relapse. Follow-up was updated in December 1989. During the last period, the overall 5-year survival improved significantly from 35% to 58% (P less than .001). The disease-free survival rose from 38% to 45% at 5 years, with median values of 15 months versus 33 months, while the frequency of isolated lung metastases dropped from 58% to the actuarial 48%. The proportion of patients who underwent complete resections of their pulmonary metastases rose from 17% (seven of 42) to 55% (27 of 49), without operative mortality. Due to such a high proportion of patients eligible for salvage surgery, the overall survival from detection of lung metastases improved from 0% to 28% at 5 years (P less than .001). Contralateral occult metastases were resected in three of 15 subjects with monolateral clinical lesions, and five patients underwent subsequent lung resections. These data indicate that systematic bilateral pulmonary resection plays an important role in improving the final cure rate of childhood osteosarcoma, beyond the benefit resulting from neoadjuvant chemotherapy.
Effect of daily etidronate on the osteolysis of multiple myeloma.
Authors: Belch A R , Bergsagel D E , Wilson K , O'Reilly S , Wilson J , Sutton D , Pater J , Johnston D , Zee B
Published: February 2017

Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma.
A randomized trial of alternating chemotherapy versus best supportive care in advanced non-small-cell lung cancer.
Authors: Cellerino R , Tummarello D , Guidi F , Isidori P , Raspugli M , Biscottini B , Fatati G
Published: February 2017

From April 1985 to September 1988, 128 patients with advanced non-small-cell lung cancer (NSCLC) were enrolled in a prospective randomized trial evaluating chemotherapy (arm A) versus best supportive care (arm B). Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression. Of the 123 patients (62 treated and 61 controls) eligible for survival, 115 were fully evaluable for response (58 treated and 57 controls). Response rates were 21% partial response, 53% stable disease, and 26% progressive disease in arm A, and 47% stable disease and 53% progressive disease in arm B. Median survival was 34.3 weeks (range, 4.3 to 218.6+ weeks) in arm A versus 21.1 weeks (range, 4.3 to 188.6 weeks) in arm B; the difference was not significant at P = .153 (Mantel-Cox). Subgroups of patients retrospectively analyzed by age, performance status, stage M0/M1, and weight loss or not showed no significant difference in survival. Poor-risk patients (at least two of the following: poor performance status, stage M1, weight loss) of arm A survived significantly longer than poor-risk patients of arm B (23.6 weeks v 12.4 weeks, Mantel-Cox P = .008); a significant difference in survival was also observed between nonsquamous cell patients of arm A and those of arm B (median survival, 38.6 weeks v 16.7 weeks; Mantel-Cox P = .041). Toxicity on the chemotherapy arm was hematologic (World Health Organization [WHO] grade greater than 3) in 12% of CE'P and in 13% of MEC' courses and gastroenteric (WHO grade greater than 3) in 24% of CE'P courses and in 8% of MEC' courses. Our alternating treatment was not significantly superior to supportive care. It is likely that certain subgroups of the NSCLC category may have an advantage with chemotherapy.
Intensive weekly chemotherapy for the treatment of extensive-stage small-cell lung cancer.
Authors: Murray N , Shah A , Osoba D , Page R , Karsai H , Grafton C , Goddard K , Fairey R , Voss N
Published: February 2017

The regimen of cisplatin, vincristine, doxorubicin, and etoposide (CODE) was designed to double the dose intensity of these drugs in comparison with a standard regimen (alternating cyclophosphamide, doxorubicin, and vincristine [CAV] and etoposide-cisplatin [EP]) for extensive-stage small-cell lung cancer (SCLC). The dose intensity was increased by more frequent treatments rather than by increasing the dose size. The structure of this outpatient protocol includes weekly administration of chemotherapy, alternation of myelosuppressive and nonmyelosuppressive treatments, supportive corticosteroids, gastroprotective agents, and prophylactic antibiotics. Although the duration of chemotherapy was brief (9 to 12 weeks), the total cumulative doses of drugs delivered were similar to the standard regimen. Patients with no residual disease outside the chest after chemotherapy received thoracic irradiation, and patients with complete responses (CRs) received prophylactic cranial irradiation. Eligible extensive-stage SCLC patients were ambulatory, younger than 66 years of age, and free of brain metastasis. Forty-eight extensive-stage SCLC patients were treated. Forty-five (94%) responded to chemotherapy, with 19 (40%) attaining CR. After consolidative thoracic irradiation, the CR rate was 56%. The median time to progression was 43 weeks, and the median survival was 61 weeks. The 2-year survival rate was 30%. The most common site of first relapse was brain (38%). Although two patients (4%) died of toxicity, overall toxicity was acceptable for an outpatient regimen. We conclude that the CODE regimen reliably produces palliative remissions for selected extensive-stage SCLC patients, and it may be associated with durable remissions for some patients. The results of this pilot study are sufficiently promising to justify a phase III trial of CODE versus standard (alternating CAV and EP) chemotherapy.
A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy.
Authors: Antman K , Ayash L , Elias A , Wheeler C , Hunt M , Eder J P , Teicher B A , Critchlow J , Bibbo J , Schnipper L E
Published: February 2017

PURPOSE

The study was designed to determine the duration of complete response (CR) for patients with unresectable or metastatic breast cancer treated with high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) while responding to conventional-dose therapy.

METHODS

Eligibility criteria included histologically documented metastatic or unresectable breast cancer, at least a partial response (PR) to conventional-dose therapy, no prior pelvic radiotherapy, cumulative doxorubicin of less than 500 mg/m3, and physiologic age between 18 and 55 years. Patients with inadequate renal, hepatic, pulmonary, and/or cardiac function or tumor involvement of marrow or CNS were excluded. Cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 were given by continuous infusion over 4 days. After recovery, sites of prior bulk disease were to be radiated or resected if feasible.

RESULTS

Of 29 registered patients, one died of toxicity (3%; hemorrhage). CRs and PRs continued a median of 16 and 5 months after transplant, respectively (26 and 9 months from initiation of chemotherapy for metastatic disease). Of 10 patients transplanted in CR, four have not progressed at 17 to 31 months after transplantation (25 to 43 months after beginning standard-dose therapy). One of four patients with uptake on bone scan as their only sites of residual disease before transplant and one of three who converted from PR to CR with transplant have not progressed at 27 and 29 months, respectively, after transplant.

CONCLUSIONS

CTCb is an intensification regimen with a low mortality that delivers a significantly increased dose of agents with known activity at conventional doses in breast cancer. Although the duration of PR is short as expected, CRs appear to be durable.
A method of predicting adult height and obesity in long-term survivors of childhood acute lymphoblastic leukemia.
Authors: Schell M J , Ochs J J , Schriock E A , Carter M
Published: February 2017

PURPOSE

Short stature and obesity have been reported among long-term survivors of childhood acute lymphocytic leukemia (ALL). We examined factors that contribute to these adverse sequelae.

PATIENTS AND METHODS

Serial height and weight measurements were analyzed for 91 long-term survivors who were treated for ALL between 1967 and 1975 at a single institution. These patients were all younger than 12 years at diagnosis, were in continuous complete remission, had reached final height, and had height and weight measurements within 1 year of age 18 years. They had received craniospinal (n = 33) or cranial irradiation (n = 58) to total doses of 24 Gy as CNS prophylaxis. Standard deviation scores (SDS) were used to reflect the deviation of height and weight measurements from population means, and the body mass index (BMI; weight divided by height squared) was used in assessing obesity at age 18 years.

RESULTS

Short stature (less than fifth percentile) was seen in 41 patients (45%), and obesity (BMI greater than or equal to 24 kg/m2) in 35 (38%). Regression formulae were developed that explain 65% and 62% of the variability in patient height and BMI, respectively.

CONCLUSIONS

Risk factors were identified for abnormally short stature, which was defined to be a decrease of 1.5 SDS in height from diagnosis to age 18 years. These factors include younger age and above-average height for age at diagnosis (height SDS greater than 0), craniospinal irradiation, and greater decrease in height SDS during antileukemic therapy. Risk factors for obesity at age 18 years include weight SDS greater than 0 and greater than height SDS at 1 year after the end of chemotherapy.
The incidence of second primary tumors in long-term survivors of small-cell lung cancer.
Authors: Heyne K H , Lippman S M , Lee J J , Lee J S , Hong W K
Published: February 2017

PURPOSE AND METHODS

A review of 446 patients who were enrolled consecutively in small-cell lung cancer (SCLC) protocols was performed to identify in long-term survivors the frequency of new primary tumors and their clinical impact.

RESULTS

Forty-seven patients (10.5%) were identified to be free of disease at 2 years. Second primary tumors (SPTs) were diagnosed in 14 patients. The overall risk for developing an SPT was 10.3% per person-year. Actuarial risk at 8 years was 50.3% for an SPT.

CONCLUSIONS

In this review, SCLC showed one of the highest incidences of SPTs reported in aerodigestive tract malignancies. A long-term survivor was more likely to have an SPT than a relapse of SCLC. Consequently, the odds of death from an SPT compared with that from a relapse increased sharply from 1:13 within 4 years from diagnosis to 8:1 afterwards. Long-term survivors of SCLC would be excellent candidates for chemoprevention trials.
Improved palliation of cerebral metastases in epithelial ovarian cancer using a combined modality approach including radiation therapy, chemotherapy, and surgery.
Authors: Rodriguez G C , Soper J T , Berchuck A , Oleson J , Dodge R , Montana G , Clarke-Pearson D L
Published: February 2017

PURPOSE

Recent reports suggest an increasing incidence of CNS metastases in patients with ovarian cancer. We reviewed our experience in the management of brain metastases from ovarian carcinoma and merged our results with those of several other series reported in the literature to determine prognostic factors and the role of chemotherapy, radiation therapy, and surgery.

PATIENTS AND METHODS

From 1977 to 1990, 15 of 795 patients who were treated for epithelial ovarian cancer at Duke University developed brain metastases. Fourteen of the patients were treated for their brain metastases; this included radiation therapy (RT; four), surgery and RT (one), RT and systemic chemotherapy (six), and all three treatment modalities (three). A meta-analysis was performed that combined the data from the current series with those of several recent clinical series that reviewed patients with brain metastases from ovarian carcinoma (67 patients total) to elucidate the impact of treatment and extent of disease on survival.

RESULTS

In the current series, median survival (MS) after the diagnosis of brain metastases was 9 months. For the combined series, MS was 5 months. Thirteen patients who were treated with whole-brain RT and systemic chemotherapy (MS, 7 months), 10 patients who were treated with RT and surgery (MS, 10 months), and nine patients who were treated with all three modalities (MS, 16.5 months) had significantly longer survival than 19 patients who were treated with RT alone (MS, 3 months) (P = .05, P = .01, and P < .001, respectively). In a multivariate analysis, the only variable that provided prognostic information was treatment, namely the addition of systemic chemotherapy or surgery to RT for the treatment of brain metastases.

CONCLUSION

Multimodal treatment of patients with brain metastases from ovarian cancer can result in significant palliation.
Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.
Authors: Oberlin O , Leverger G , Pacquement H , Raquin M A , Chompret A , Habrand J L , Terrier-Lacombe M J , Bey P , Bertrand Y , Rubie H
Published: February 2017

PURPOSE

With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy.

PATIENTS AND METHODS

A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered.

RESULTS

At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results.

CONCLUSIONS

Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.
High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma.
Authors: Lazarus H M , Crilley P , Ciobanu N , Creger R J , Fox R M , Shina D C , Bulova S I , Gucalp R , Cooper B W , Topolsky D
Published: February 2017

PURPOSE

We determined the toxicity and efficacy of a new preparative autologous bone marrow transplantation (ABMT) regimen in patients with relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease.

PATIENTS AND METHODS

Forty-four non-Hodgkin's lymphoma and 35 Hodgkin's disease patients 16 to 63 years of age were given intravenous carmustine (BCNU) 600 to 1,050 mg/m2, etoposide 2,400 to 3,000 mg/m2, and cisplatin 200 mg/m2 (BEP) and ABMT. Fifty-nine patients also received 15 to 20 Gy local radiation (involved-field radiotherapy [RI]) to active or previously bulky (> 5 cm) disease sites.

RESULTS

Nonhematologic toxicities included nausea, vomiting, high-tone hearing loss, stomatitis, esophagitis, diarrhea, and hepatic and pulmonary toxicity. Two patients died within 40 days of marrow infusion as a result of sepsis and one patient died 7 months after transplant as a result of pulmonary fibrosis. Complete remissions (CRs) were noted in 72% (n = 57) of patients (n = 33 non-Hodgkin's lymphoma; n = 24 Hodgkin's disease). Forty patients (51%) remained alive and disease-free (n = 24 non-Hodgkin's lymphoma; n = 16 Hodgkin's disease) at a median of 17 (range, 8 to 57) months after marrow reinfusion.

CONCLUSIONS

This regimen seems to be effective for relapsed lymphoma patients whose disease continues to exhibit chemotherapy sensitivity (16 of 24 [67%] disease-free). Furthermore, this regimen seems to be effective in patients who have never attained a CR (seven of 19 [37%] disease-free).
Phase I and II study of high-dose ifosfamide, carboplatin, and etoposide with autologous bone marrow rescue in lymphomas and solid tumors.
Authors: Wilson W H , Jain V , Bryant G , Cowan K H , Carter C , Cottler-Fox M , Goldspiel B , Steinberg S M , Longo D L , Wittes R E
Published: February 2017

PURPOSE

High-dose chemotherapy produces durable disease-free remissions in a minority of patients with resistant lymphomas and solid tumors. In an attempt to improve on the available regimens, ifosfamide, carboplatin, and etoposide (ICE) were selected for a new high-dose regimen because of their favorable spectrum of nonhematopoietic toxicity and evidence of synergy in in vitro systems.

PATIENTS AND METHODS

Forty-one patients with drug-resistant Hodgkin's and non-Hodgkin's lymphomas, and breast and testicular cancers were entered onto a phase I and II trial of a single course of ICE with autologous bone marrow rescue. Before transplantation, all patients received combination chemotherapy until maximal tumor response was achieved.

RESULTS

Patients received total doses of ifosfamide from 10 to 18 g/m2, carboplatin from 0.9 to 1.98 g/m2, and etoposide from 0.6 to 1.5 g/m2 administered during a 4-day period, with a maximum-tolerated dose (MTD) of ifosfamide 16 g/m2, carboplatin 1.8 g/m2, and etoposide 1.5 g/m2. The dose-limiting toxicities included irreversible renal, cardiac, and CNS dysfunction. There were three toxic deaths (7%), and all occurred above the MTD. Thirteen patients who were treated at the MTD tolerated the regimen well; reversible renal dysfunction and grade 2 mucositis commonly were observed. Of 23 heavily pretreated patients with persistent disease at the time of transplant, 10 (43%) achieved complete remissions (CRs) and 11 (48%) achieved partial remissions (PRs). Hodgkin's and non-Hodgkin's lymphoma patients who were treated at or below the MTD had a median potential follow-up of 11.9 months, and 12-month progression-free survivals of 62% and 48%, respectively.

CONCLUSION

High-dose ICE with bone marrow rescue was well tolerated with a high response rate, and should be considered for further testing.
Ifosfamide plus etoposide in newly diagnosed Ewing's sarcoma of bone.
Authors: Meyer W H , Kun L , Marina N , Roberson P , Parham D , Rao B , Fletcher B , Pratt C B
Published: February 2017

PURPOSE

We assessed the activity of ifosfamide plus etoposide against newly diagnosed Ewing's sarcoma of bone by administering this drug pair before standard induction therapy (the upfront window approach).

PATIENTS AND METHODS

Twenty-six children and adolescents with newly diagnosed, previously untreated Ewing's sarcoma of bone were enrolled onto this pilot study (EW-87). Eighteen were at a higher risk of treatment failure, with a primary tumor size of more than 8 cm or metastases at diagnosis. Window therapy with ifosfamide (1.6 g/m2/d with mesna uroprotection) and etoposide (100 mg/m2/d) was given in three 5-day cycles at 21-day intervals. Responses were evaluated clinically and radiologically. Subsequent induction therapy comprised three cycles of cyclophosphamide and doxorubicin. Radiation therapy was the primary local control modality; surgery was limited to biopsy or resection of expendable bones. After the local control phase, alternating courses of vincristine plus dactinomycin, ifosfamide plus etoposide, and cyclophosphamide plus doxorubicin were given as maintenance therapy.

RESULTS

There were four complete responses and 21 partial responses to ifosfamide/etoposide window therapy (overall response rate 96%; 95% confidence interval [CI], 80% to 99%). Disease progression was observed in four patients during the cyclophosphamide/doxorubicin phase. Chemotherapy was well tolerated; only 16% (20 of 125) of all ifosfamide/etoposide window and maintenance cycles resulted in hospitalization for fever and neutropenia. Two patients developed chemotherapy-induced cystitis.

CONCLUSIONS

The combination of ifosfamide and etoposide is highly active against previously untreated Ewing's sarcoma and generally is well tolerated. The ultimate impact of these two agents on outcome will be determined in randomized multicenter studies.
Prognostic value of DNA flow cytometry in the locally recurrent, conservatively treated breast cancer patient.
Authors: Haffty B G , Toth M , Flynn S , Fischer D , Carter D
Published: February 2017

PURPOSE

This study attempted to determine the prognostic value of DNA flow cytometry in the treatment of patients with locally recurrent, conservatively treated breast cancer.

METHODS AND MATERIALS

Of 433 patients with clinical stage I and II breast cancer treated with conservative surgery and radiotherapy at Yale-New Haven Hospital before January 1985, 50 patients experienced an ipsilateral breast relapse as a first site of treatment failure. Using standard flow-cytometric techniques, DNA ploidy, DNA index, and S-phase fraction (SPF) were measured for 38 of the 50 (76%) paraffin-embedded specimens available for analysis.

RESULTS

At a median postrecurrence follow-up of 5.8 years, the 5-year and disease-free survival rates following ipsilateral breast treatment failure were 48% and 54%, respectively. Sixty-three percent of the recurrent tumors were DNA diploid and 37% were aneuploid. Both DNA ploidy and SPF were statistically significant prognostic indicators for 5-year survival and disease-free survival after local recurrence. The 5-year survival rate of the DNA diploid population was 64%, compared with 15% in the aneuploid population (P < .02). Patients with low SPF (< 12%) experienced an 83% 5-year survival rate, compared with a 24% 5-year survival rate in patients with high SPF (> or = 12%) (P < .03). Ploidy and SPF were combined to define the categories of favorable (diploid, low SPF) and unfavorable (diploid, high SPF or any aneuploid subgroups). Patients in the favorable category experienced an 89% 5-year postrecurrence survival rate and a 100% disease-free survival rate, whereas patients in the unfavorable category had a 24% 5-year survival rate and a 32% disease-free survival rate (P < .01). The flow cytometry as a factor correlated with other clinical parameters previously shown to be of prognostic significance in this patient population. In a multivariate analysis, flow cytometry was a statistically significant and independent prognostic factor for disease-free survival following local recurrence.

CONCLUSIONS

DNA ploidy and SPF as measured by currently available flow-cytometric techniques show promise as a tool in determining prognosis for the patient with locally recurrent breast cancer. Implications of these findings with respect to issues of adjuvant systemic therapy at the time of local recurrence are discussed.
Treatment of recurrent and refractory pediatric solid tumors with high-dose busulfan and cyclophosphamide followed by autologous bone marrow rescue.
Authors: Graham M L , Yeager A M , Leventhal B G , Wiley J M , Civin C I , Strauss L C , Hurwitz C A , Dubowy R L , Wharam M D , Colombani P M
Published: February 2017

PURPOSE

The purpose of this study was to determine the toxicities of and responses to high-dose busulfan and cyclophosphamide with autologous bone marrow transplant (ABMT) in patients with recurrent or refractory pediatric solid tumors.

PATIENTS AND METHODS

We treated 18 patients (ages, 2 to 38 years; median, 14) who had tumors that were resistant to conventional chemotherapy and radiotherapy with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg. Seventeen patients received bone marrow purged with 4-hydroperoxycyclophosphamide; one received unpurged marrow.

RESULTS

Despite extensive prior treatment, including radiotherapy in 16 patients, toxicity generally was acceptable. For seven patients with measurable disease, there were three partial responses of 2, 10, and 20 months' duration, three patients with stable disease (SD), and one early, toxic death. Of the 11 patients with no measurable disease at the time of transplantation, one patient with osteosarcoma continues in remission at 57+ months and one third of the patients survived for at least 16 months. Mucositis was the predominant nonhematopoietic toxicity.

CONCLUSION

Although the high-dose busulfan and cyclophosphamide combination showed modest activity, changes in the preparative regimen should be considered to improve the response rate in refractory tumors.
Standard-dose and high-dose peptichemio and cisplatin in children with disseminated poor-risk neuroblastoma: two studies by the Italian Cooperative Group for Neuroblastoma.
Authors: De Bernardi B , Carli M , Casale F , Corciulo P , Cordero di Montezemolo L , De Laurentis C , Bagnulo S , Brisigotti M , Marchese N , Garaventa A
Published: February 2017

PURPOSE

The objective of the present study was to determine whether an increase in the intensity of therapy improves outcome for children with disseminated poor-risk neuroblastoma.

PATIENTS AND METHODS

From January 1982 through November 1989, 181 children 1 year or older with newly diagnosed disseminated neuroblastoma were entered onto two consecutive studies of the Italian Cooperative Group for Neuroblastoma (ICGNB): 75 (study NB82) were enrolled from 1982 to 1984 and were treated with standard-dose (SD) chemotherapy, and 106 (study NB85) were enrolled from 1985 to 1989 and received high-dose (HD) chemotherapy. In both treatment protocols, induction therapy included peptichemio and cisplatin (at SD or HD, respectively) and removal of the primary tumor. In study NB82, children who achieved complete or partial tumor regression received SD consolidation therapy, and in study NB85 they received three cycles of HD chemotherapy (3cCT) or one cycle of myeloablative therapy (MAT) followed by autologous bone marrow transplantation (ABMT).

RESULTS

Compared with group NB82, the NB85 group had significantly fewer failures (no tumor response or disease progression) after administration of peptichemio (9% v 31%; P < .01), had more complete responses (CRs) and partial responses (PRs) both after treatment with cisplatin (60% v 43%; P = .01) and after surgery (76% v 57%; P < .01), and was more likely to have achieved complete excision of the primary tumor (70% v 46%; P < .01). Overall survival (OS) and progression-free survival (PFS) at 5 years were 11% and 9% in NB82, and 27% and 18% in NB85 (P < .01 for both); however, in NB85, relapses occurred even after 5 years of CR, so that PFS curves converge approximately 7 years after diagnosis. Median survival time was 14 months in NB82 and 24 months in NB85. Children in the NB85 group who after achievement of CR were consolidated with 3cCT had a 5-year PFS of 24% compared with 32% of those treated with MAT followed by ABMT (P = .5).

CONCLUSION

Intensified therapy improves response rate and prolongs survival of children with disseminated neuroblastoma, although its impact on the eventual cure rate remains to be established.
Residual disease at the end of induction therapy as a predictor of relapse during therapy in childhood B-lineage acute lymphoblastic leukemia.
Authors: Wasserman R , Galili N , Ito Y , Silber J H , Reichard B A , Shane S , Womer R B , Lange B , Rovera G
Published: February 2017

PURPOSE

More than 95% of children with B-lineage acute lymphoblastic leukemia (ALL) achieve a clinical remission after the induction phase of chemotherapy (first 28 days) as evaluated by morphologic criteria. However, relapse occurs in approximately 30% of these children. The objective of this study was to determine whether the outcome of patients in clinical remission at the end of induction therapy could be predicted using a highly sensitive method to detect residual disease.

PATIENTS AND METHODS

All children diagnosed with B-lineage ALL at the Children's Hospital of Philadelphia during a 2-year period were eligible. The extent of residual leukemia was quantitated in remission marrow samples obtained at the end of induction therapy in 44 children using a phage clonogenic assay in association with complementarity-determining-region 3 (CDR3)-polymerase chain reaction (PCR).

RESULTS

Residual disease was a significant predictor of outcome independent of WBC count, age, or sex. The estimated relapse-free survival (RFS) during therapy was 50.4% (+/- 12.6%) for patients with high residual disease (> or = 0.6% leukemia cells among total marrow B cells) versus 91.9% (+/- 5.5%) for those with lower levels (P < .002). There were no significant differences in off-treatment RFS between patients with high or low residual disease who completed therapy in continuous remission (P = .82). The overall estimated RFS was 32.3% (+/- 11.6%) for patients with high residual disease versus 62.6% (+/- 10.7%) for patients with lower levels of residual leukemia cells, with a median follow-up of 5.3 years for patients in continuous remission (P < .008).

CONCLUSION

PCR detection of high residual disease at the end of induction therapy identifies patients at increased risk for relapse during therapy.
A prospective randomized trial comparing the infectious and noninfectious complications of an externalized catheter versus a subcutaneously implanted device in cancer patients.
Authors: Mueller B U , Skelton J , Callender D P , Marshall D , Gress J , Longo D , Norton J , Rubin M , Venzon D , Pizzo P A
Published: February 2017

PURPOSE

To compare the frequency of infectious episodes or other problems occurring with an externalized catheter (Hickman) versus a subcutaneously implanted device (Port-a-Cath, Pharmacia, Piscataway, NJ) in cancer patients, we performed a prospective, randomized study in 100 cancer patients (age range, 5 to 74 years).

PATIENTS AND METHODS

Patients who were chemotherapy candidates and required an indwelling catheter were monitored prospectively and evaluated during the 180 days after the insertion of the catheter and again at time of study closure. The frequency of catheter use, reason for access, and any problems that might have been related to catheter use were noted. All data were collected prospectively and included the patient's age, sex, underlying malignancy, temperature, and leukocyte and absolute granulocyte counts at the time of catheter insertion and when complications occurred. The time to and reason for removal of the catheter, as well as any intercurrent infectious or mechanical problems, were also determined.

RESULTS

Most of the infections that occurred were caused by gram-positive organisms, especially staphylococci or streptococci. A total of 22 complications (11 in each group) resulted in removal of the central line. Only one infection in the Hickman catheter group and four in the Port-a-Cath group led to removal of the central line. All other infectious episodes were successfully treated without removal of the catheters. The mean device life was 230 days for the Hickman catheter and 318 days for the Port-a-Cath (not significant).

CONCLUSION

There were no differences between the two study groups regarding incidence of documented infections or mechanical or thrombotic complications.
MACOP-B treatment in diffuse large-cell lymphoma: identification of prognostic groups in an Italian multicenter study.
Authors: Vitolo U , Bertini M , Brusamolino E , Cavallero G B , Comotti B , Gallo E , Ghio R , Levis A , Luxi G , Meneghini V
Published: February 2017

PURPOSE

The prognosis of advanced-stage diffuse large-cell lymphoma (DLCL) has improved with the use of the third-generation regimens such as methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B). However, different results have been reported. Therefore, we started a cooperative study to confirm the efficacy of MACOP-B. An analysis of prognostic factors was also performed to identify poor-prognosis patients.

PATIENTS AND METHODS

Between June 1986 and March 1989, 180 patients with advanced-stage DLCL were treated with MACOP-B. MACOP-B was given according to the original scheme. Numerous clinical features possibly predictive for complete response (CR), disease-free survival (DFS), and survival were analyzed in univariate and multivariate analyses.

RESULTS

One hundred twenty-seven patients (71%) achieved a complete remission, 20 (11%) achieved a partial remission, 24 (13%) had unchanged or progressive disease, and nine (5%) died due to toxicity. With a median follow-up of 28 months, 71% of 127 CRs remain in first remission. Predicted 3-year survival for all 180 patients is 60%, and 3-year DFS for the 127 CRs is 67%. Overall toxicity was acceptable, with mucositis being the most frequent severe side effect. A multivariate regression analysis identified lactate dehydrogenase (LDH) level, bone marrow involvement, and tumor burden as independent risk factors for survival. These factors were also important for achievement of remission and DFS and allowed us to identify three distinct risk groups of patients with good, intermediate, and poor prognosis, with 3-year survival rates of 80%, 59%, and %29, respectively.

CONCLUSIONS

These results confirm the effectiveness of MACOP-B in advanced-stage DLCL at low or intermediate risk; however, high-risk patients are in urgent need of new therapeutic approaches. A better definition of prognostic features would allow a more reliable comparison of different treatment regimens, as well as an effective tailoring of therapy by prognostic groups.
Telephone counseling improves adherence to colposcopy among lower-income minority women.
Authors: Lerman C , Hanjani P , Caputo C , Miller S , Delmoor E , Nolte S , Engstrom P
Published: February 2017

PURPOSE

A randomized trial was conducted to evaluate the impact of a telephone counseling intervention to improve patient adherence to colposcopic examination for suspected cervical intraepithelial neoplasia (CIN).

METHODS

Subjects were lower-income, minority women who missed a scheduled initial appointment for colposcopy at an urban medical clinic. Patients were randomly assigned to either a control condition (n = 42) or a telephone counseling condition (n = 48). The 15-minute, structured telephone counseling intervention protocol addressed educational, psychosocial, and practical barriers to colposcopy adherence.

RESULTS

The most common patient-reported barriers to colposcopy adherence included a lack of understanding of the purpose of colposcopy (50%), worry about or fear of cancer (25%), and forgetting (23%). Telephone counseling was found to be highly effective in addressing these barriers and improving adherence to diagnostic follow-up and treatment. Of patients in the control condition, 43% complied with a rescheduled colposcopy appointment, compared with 67% in the telephone counseling condition. Logistic regression analysis indicated that the effect of telephone counseling was independent of sociodemographic confounder variables (odds ratio = 2.6; P less than .003). Additionally, 74% of patients who received the initial telephone counseling adhered to recommended treatment, compared with 53% of patients in the control condition.

CONCLUSION

Brief, structured telephone contact may be a cost-effective mechanism for improving adherence to diagnostic follow-up and treatment for a variety of cancer screening tests.
Aromatase activity and estradiol in human breast cancer: its relationship to estradiol and epidermal growth factor receptors and to tumor-node-metastasis staging.
Authors: Bolufer P , Ricart E , Lluch A , Vazquez C , Rodriguez A , Ruiz A , Llopis F , Garcia-Conde J , Romero R
Published: February 2017

PURPOSE

The present report attempts to clarify whether there is a relationship between aromatase activity (ARAC) and estradiol (E2), hormonal receptors, E2 receptor (ER), and epidermal growth factor receptor (EGFR), as well as with tumor stage and histopathology in human breast cancers.

MATERIALS AND METHODS

We studied 225 breast carcinomas, 67 of which were premenopausal and 158 postmenopausal. In each sample, ARAC, EGFR, ER, and E2 were quantified. ARAC was quantified by Thompson and Siiterii's method, EGFR was quantified with a two-point assay method using radioactive iodine (125I)-EGF as ligand, and ER was measured by the Scatchard method using 3H-E2. E2 was quantified by radioimmunoassay in the diethylether tumor extract.

RESULTS

ARAC was found in 64% of the cancers studied. There is a strong direct association between ARAC and tumor size in postmenopausal patients (P = .001). In the postmenopausal group, the proportion of ARAC-positive (ARAC+) tumors is significantly higher among ER-positive (ER+) than ER-negative (ER-) ones (P less than .001). ER+ tumors also have significantly higher levels of E2 than do ER- ones (P less than .0001); similarly, ARAC+ tumors have significantly higher levels of E2 than do ARAC- ones (P less than .0001). There is a significant multiple linear correlation between the log of the levels of ARAC, ER, and EGFR and the log of tumor E2 (P less than .0001). The correlation coefficients obtained show that ARAC and ER have a positive effect on tumor E2.

CONCLUSION

The results obtained suggest the importance of tumor ARAC in the tumoral levels of E2 and reinforce the possible biologic significance of tumor ARAC, especially in postmenopausal breast carcinoma patients.
Curability of solitary bone plasmacytoma.
Authors: Dimopoulos M A , Goldstein J , Fuller L , Delasalle K , Alexanian R
Published: February 2017

PURPOSE

The effects of involved-field radiotherapy were assessed in patients with a solitary plasmacytoma of bone (SBP).

PATIENTS AND METHODS

Forty-five consecutive patients with an SBP received megavoltage irradiation of at least 3,000 cGy. The median age was 53 years, 67% of patients showed a myeloma protein, and uninvolved immunoglobulins (Igs) were preserved in 93% of patients.

RESULTS

Permanent control of presenting disease was achieved in all but two patients, but 46% of patients developed multiple myeloma. When it occurred, progression of myeloma occurred within 3 years in two thirds of the patients, suggesting that the extent of disease was understaged at diagnosis. Myeloma protein disappeared in nine patients (30%) whose disease has not yet recurred. The median survival for all patients was 13 years and the myeloma-specific survival fraction at 10 years was 53%.

CONCLUSION

In patients with an SBP, the disappearance of myeloma protein with involved-field radiotherapy predicted long-term disease-free survival and possible cure. Nonsecretory disease and persistent myeloma protein after treatment were adverse prognostic factors for which adjuvant therapy with interferon alfa should be considered.
Treatment of bone metastases with dichloromethylene bisphosphonate.
Authors: Francini G , Gonnelli S , Petrioli R , Conti F , Paffetti P , Gennari C
Published: February 2017

PURPOSE

The study was undertaken to evaluate the effects of dichloromethylene bisphosphonate (Cl2MDP) on osteolytic and osteoblastic bone lesions from a variety of tumoral primary sites and to investigate the in vivo mechanism underlying the action of this drug.

PATIENTS AND METHODS

Seventy-six patients participated in the current study: 59 had predominantly osteolytic lesions and 17 osteoblastic metastases. Sixteen patients had hypercalcemia. All of the patients received 300 mg of Cl2MDP intravenously (IV) for 7 days and then 200 mg of Cl2MDP intramuscularly (IM) for 14 days. Biochemical parameters were measured in the patients before the start of treatment and 3, 7, 14, and 21 days after beginning treatment. After the withdrawal of parenteral Cl2MDP, 59 patients with predominantly osteolytic lesions were then randomized to receive chemotherapy alone (group A, 29 cases) or chemotherapy plus Cl2MDP given at an oral dose of 1,200 mg/d (group B, 30 cases).

RESULTS

Serum calcium (Ca), urinary calcium (UCa) phosphate (UPO4), and hydroxyproline (HOP) excretion levels significantly decreased in all patients, whereas no significant changes occurred in serum alkaline phosphatase (AlkPh) and bone Gla-protein (BGP) levels. In 56 patients with painful bone lesions, a progressive analgesic effect was observed mainly between day 7 and day 14. In patients with predominantly osteoblastic metastases, the Cl2MDP treatment led to a more evident hypocalcemia and an increase in both AlkPh and BGP. However, in the majority of these patients the hypocalcemia was corrected by the concurrent use of effective cytotoxic treatments capable of reducing osteoblast stimulation. During 6 months of follow-up, two pathologic fractures occurred in patients of group A, and none occurred in patients of group B.

CONCLUSIONS

We conclude that Cl2MDP was effective in patients presenting bone metastases with and without hypercalcemia. Care should be taken particularly in those patients with mixed metastases when the sclerotic component is predominant, as the drug may enhance the possibility of hypocalcemia, which is generally corrected by effective cytotoxic drugs. Therefore, Cl2MDP can be considered a valuable support in the treatment of bone metastases.
Human breast cancer: prognostic significance of the c-erbB-2 oncoprotein compared with epidermal growth factor receptor, DNA ploidy, and conventional pathologic features.
Authors: Gasparini G , Gullick W J , Bevilacqua P , Sainsbury J R , Meli S , Boracchi P , Testolin A , La Malfa G , Pozza F
Published: February 2017

PURPOSE

A study was undertaken to define the prognostic value of the expression of the c-erbB-2 oncoprotein in a series of breast cancer patients when compared by multivariate analysis with expression of the epidermal growth factor receptor (EGFR), DNA ploidy, and conventional clinicopathologic features.

PATIENTS AND METHODS

Prognostic indicators were analyzed in 165 primary breast cancers. The c-erbB-2 oncoprotein was recognized by the polyclonal antibody 21N using an immunocytochemical method. Expression of the EGFR was stated immunocytochemically using the monoclonal antibody EGFR1. DNA ploidy was assessed in paraffin-embedded sections using a standard flow-cytometric method.

RESULTS

Overall, 27% of carcinomas had membrane 21N-staining and were classified as c-erbB-2-positive. Overexpression of the c-erbB-2 oncoprotein was poorly associated with EGFR expression and the conventional pathologic features, and it was weakly associated with DNA ploidy and nodal status. Univariate analysis showed that c-erbB-2 expression, nodal status, DNA ploidy, and EGFR provided significant prognostic information concerning 4-year relapse-free survival (RFS) with the odds ratios (ORs) of not relapsing of 2.94, 2.83, 2.34, and 2.20, respectively. Regarding overall survival (OS) at 4 years, only nodal status and DNA ploidy had prognostic significance, with the ORs of not dying of 2.68 and 2.80, respectively. Applying multivariate analysis to RFS, 21N when adjusted for nodal status, EGFR, and DNA ploidy (full model) failed to retain prognostic value (P = .202), whereas nodal status was the most significant indicator of relapse (P = .027) followed by DNA ploidy (P = .056) and EGFR (P = .093).

CONCLUSIONS

This study suggests that overexpression of the c-erbB-2 oncoprotein appears to be an important indicator of relapse in stage I-II breast cancer when singly evaluated. Multivariate analysis shows that the determination both of nodal status and DNA ploidy improves our ability to identify subsets of patients with different prognoses, and allows for a better selection of patients for systemic adjuvant treatments.
Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer.
Authors: Alberts D S , Green S , Hannigan E V , O'Toole R , Stock-Novack D , Anderson P , Surwit E A , Malvlya V K , Nahhas W A , Jolles C J
Published: February 2017

PURPOSE

To compare cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide as primary chemotherapy for stage III (suboptimal) and stage IV ovarian cancer.

PATIENTS AND METHODS

Three hundred forty-two patients were randomly assigned to treatment with six courses of intravenous (i.v.) cisplatin 100 mg/m2 plus i.v. cyclophosphamide 600 mg/m2, or i.v. carboplatin 300 mg/m2 plus i.v. cyclophosphamide 600 mg/m2.

RESULTS

The estimated median survivals were 17.4 and 20.0 months for the cisplatin and carboplatin study arms, respectively. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the P = .02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. Pathologic complete response rates were similar for both study arms. There was less thrombocytopenia on the cisplatin arm (P less than .001); however, there was less nausea and emesis (P less than or equal to .001 for courses 1 to 5), renal toxicity (P less than .001), anemia (P = .01), hearing loss (P less than .001), tinnitus (P = .01), neuromuscular toxicities (P = .001), and alopecia (P less than .001) on the carboplatin arm.

CONCLUSION

Carboplatin-cyclophosphamide proved to have a significantly better therapeutic index than cisplatin-cyclophosphamide in patients with stage III (suboptimal) and stage IV ovarian cancer.