A. Kuten

MALE GONADAL FUNCTION IN SURVIVORS OF CHILDHOOD HODGKIN AND NON-HODGKIN LYMPHOMA

The aim of this study was to investigate the impact of therapy on long-term gonadal function of young people cured of childhood lymphomas and to assess whether a prepubertal state during the treatment protects the gonads from chemotherapy and/or radiotherapy late effects. Clinical evaluation, semen analysis, and endocrine status were studied in 20 survivors of childhood lymphomas. Five patients received Inverted Y radiotherapy, 2320 cGy (1550-4000); all 20 received chemotherapy as follows: MOPP/ABVD protocol, 9 patients; COMP protocol, 5 patients; MOPP protocol, 3 patients; other protocols, 3 patients. Semen analysis results were as follows: normal values, 4/20 patients; oligospermia, 8/20 patients; azoospermia, 8/20 patients; FSH above normal level, 10/20 patients; 4/5 who received Inverted Y irradiation were azoospermic and 1 was severely oligospermic. Treatment damage to the testis involves tubular germinal elements. Radiotherapy and chemotherapy combinations that included nitrogen mustard or cyclophosphamide were associated with high rates of oligospermia and azoospermia. MOPP/ABVD combination did not have a significant better outcome of sperm counts compared to MOPP alone. Age at chemotherapy did not correlate with the sperm count; hence a prepubertal state did not protect the gonad from the late effects of treatment.

Octreotide in the treatment of severe chemotherapy-induced diarrhea

BACKGROUND Chemotherapy-induced diarrhea (CID) is a common side effect of a number of chemotherapeutic agents. Conventional therapy for severe CID with opioids or loperamide is moderately effective. A prospective trial was conducted using octreotide acetate for treatment of severe CID refractory to loperamide. PATIENTS AND METHODS Thirty-two patients with grade 2 and 3 CID refractory to loperamide were treated with octreotide at a dosage of 100 microg subcutaneously 3x/day for three days followed by 50 microg 3x/day for three days. Previous chemotherapy consisted of regimens containing fluorouracil, leucovorin, CPT-11, cyclophosphamide, methotrexate and cisplatin. Primary tumors were colorectal (n = 23), gastric (n = 3), and other cancers (n = 6). RESULTS Complete resolution of diarrhea was obtained in 30 of 32 patients (94%); 5 within 24 hours, 14 within 48 hours, and 11 within 72 hours of treatment. Nineteen patients were treated as outpatients. Thirteen were hospitalized for a median of three days. Response was unaffected by age, gender, performance status, previous chemotherapy or primary tumor site. No side effects related to octreotide were observed. CONCLUSIONS Octreotide 100 microg subcutaneously 3x/day for three days is an effective, safe treatment for CID given primarily or as a second-line therapy after loperamide failure.

Primary Lymphoma of Bone – A Retrospective Study

Objective: This retrospective study describes our experience with the diagnosis, treatment, results and long-term follow-up of primary bone lymphoma (PBL). Patients and Methods: Nineteen patients diagnosed with PBL were reviewed. Seven patients presented with stage IE disease, four with stage IIE (regional lymphadenopathy), and eight with stage IV disease (disseminated bone involvement). Only one stage IV patient exhibited ‘B’ symptoms. The majority (72%) demonstrated diffuse, large cell, B-type lymphoma. All patients were treated with adriamycin-based chemotherapy and consolidation radiotherapy to the primary site (8 patients: early PBL) or the most bulky area (3 patients: stage IV PBL). Results: Ten stage IE/IIE patients are alive with no evidence of disease (NED) and only one died due to metastatic secondary lung cancer while with NED from his PBL. Eight stage IV patients are alive with NED. Median follow-up for all living patients: 77 months. Side effects were mild and did not necessitate delay in treatment. Conclusions: Our departmental policy of treating PBL patients with an anthracycline-based regimen and involved field radiotherapy proved to be successful in achieving excellent long-term, disease-free survival. Phase III randomized, controlled, clinical trials will determine the true role of consolidation radiotherapy in PBL, when considering severe late side effects, including radiation-induced bone tumors.

LONG-TERM FOLLOW-UP OF CHILDREN WITH RETINOBLASTOMA

Twenty-one pediatric retinoblastoma (RB) patients treated between 1976 and 1994 were evaluated for late treatment-related complications. Median age at diagnosis was 24 months; median age at follow-up was 12 years; median follow-up time was 12 years. Of the 21 patients, 14 had unilateral RB and 7 had bilateral RB. Thirteen patients had received external radiotherapy and 8 children were treated by chemotherapy. Twenty-one patients had undergone enucleation. Radiation-induced cataracts were found in 3 patients, radiation retinopathy in 1, enucleation and postradiotherapy contracted socket in 1, very low visual acuity postradiotherapy in 3, severe hypotelorism in 2, growth hormone deficiency in 2, neurocognitive disorders in 6, and orbital deformation due to radiation bone atrophy was moderate-severe in 12 patients. Azoospermia was found in 1 patient treated by cyclophosphamide and vincristine. The most frequent sequela in this group of RB-cured children were postradiotherapy orbital deformation due to bone atrophy and neurocognitive disabilities. Late radiation effects must be avoided by using modern, innovative, and more sophisticated radiotherapeutic techniques. Late treatment-related complications justify the long-term follow-up of childhood RB survivors.

Intensive chemotherapy using cisplatin and fluorouracil followed by radiotherapy in advanced head and neck cancer

This protocol was designed to achieve an improvement in the overall and disease-free survival in locally advanced, previously untreated carcinoma of the head and neck. 53 patients (pts) with locally advanced Stages III and IV, MO squamous cell carcinoma of the nasopharynx, larynx, paranasal sinuses, oral cavity, oropharynx, hypopharynx and one of unknown origin were treated with intensive chemotherapy followed shortly thereafter by radiotherapy. Induction chemotherapy consisted of two cycles of cisplatin 100 mg/m2 over 60 min on day 1, plus 5FU 1000 mg/m2 continuous infusion over 24 h on days 2-5, with a 10-day interval between the two cycles, followed by definitive radiotherapy after 10 days. The overall response rate to chemotherapy was 79%, with a 28% complete response (CR) rate and a 51% partial response (PR) rate. The overall CR rate after radiotherapy was 70%. With a median follow-up period of 48 months, the 5-year actuarial survival and disease-free survival rates were 67% and 45%, respectively. No difference was found in the survival probability of pts with carcinoma of the nasopharynx, larynx or other primary sites. The survival of pts with a performance status (PS) < or = 1 was better than pts with PS > 1, 72% versus 51% (not significant). The survival probability of complete responders to chemotherapy was superior than the survival of non-complete responders to chemotherapy, 100% versus 54% [P = 0.001]. The main toxicity was mucositis during radiotherapy. In conclusion, this treatment regimen demonstrated a high CR rate and survival probability in pts with locally advanced and mostly inoperable head and neck cancer.

Neurologic complications in pediatric solid tumors.

The cases of 61 children, consecutively diagnosed during 1986-1990 as having malignant solid tumors (but excluding those with brain tumors and lymphoproliferative diseases), were reviewed. Neurologic complications occurred in 19 (31%), most often in association with neuroblastomas and sarcomas. Complications observed in order of frequency were: brain metastases in 6 children, spinal cord compression in 5, peripheral or cranial neuropathies in 4, and seizures in the remaining 4. Early recognition of neurologic compromise and rapid initiation of treatment are mandatory in order to prevent permanent disability.

Advanced Nasopharyngeal Carcinoma in the Young: The Northern Israel Oncology Center Experience, 1973–1991

Between 1973 and 1991, 10 patients with locally advanced [stages III and IV] nasopharyngeal carcinoma were treated at the Northern Israel Oncology Center. All patients were treated with wide-field irradiation to the primary tumor, including the base of skull, neck, and supraclavicular region. After 1984, 6 patients also received cisplatin/5FU-based chemotherapy prior to radiotherapy and 1 patient received it after radiotherapy. All the patients who received chemotherapy are alive with no evidence of disease, for a mean disease-free survival of 96 months (range, 77 to 108 months), and no serious therapy-related late side-effects have been noted, except in one patient. We conclude that adjuvant chemotherapy may be effective in improving outcome, but only randomized prospective studies can evaluate its exact role.

Multifocal Desmoid Tumor in Childhood: Report of Two Cases and Review of the Literature

We present two cases of multifocal desmoid tumors arising in two teenagers. Different, separate lesions developed in the same limb over a period of several years, one of which recurred on several occasions. The literature regarding the therapeutic aspects of multifocal fibromatosis is reviewed and discussed.

THE ROLE OF CHEMOTHERAPY IN CHILDHOOD SOFT TISSUE SARCOMAS OTHER THAN RHABDOMYOSARCOMAS: Experience of the Northern Israel Oncology Center

Forty-three children with nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) were treated at the Northern Israel Oncology Center in Haifa, Israel, from 1971 to 1996. The male:female ratio was 1.5:1 and the median age of patient was 10 years (range, 3 months-18 years). The most common histopathologic diagnoses were fibrosarcoma (32.5%) and synovial sarcoma (16%). The sites of primary tumor were lower limb (35%), trunk (18%), upper limb (16%), head and neck (16%), and retroperitoneum (11%). By Intergroup Rhabdomyosarcoma Study classifications, 13 patients presented as group I, 15 patients as group II, 10 patients as group III, and 5 patients as group IV. Median follow-up time was 63 months (range, 6 months-18 years). The estimated survival after a 5-year period is 72% (SE +/- 17) for patients in group I, 75 +/- 15% in group II, 90 +/- 9% for patients in group III, and 40 +/- 21% for patients in group IV. Eleven patients relapsed; 4/6 who developed local relapse were cured and are alive with disease, while 4/5 who developed distant metastases are dead. For the 28 patients who underwent complete resection at diagnosis, the estimated survival after a 5-year period is 87 +/- 5% vs. 60 +/- 17% for the 15 patients who underwent partial excision or biopsy. Local radiotherapy was delivered after surgery to group III patients. Preoperative and postoperative chemotherapy was delivered to the patients of groups III and IV, and postoperative chemotherapy only to group II patients. Chemotherapy produced demonstrable gain in survival for group II and III patients but not for patients with metastases. The authors conclude that an aggressive surgical approach is needed in patients with NRSTS. Chemotherapy may help as a preoperative treatment in bulky disease or as a postoperative treatment for microscopic residual disease.

Testicular seminoma: 20-year experience at the Northern Israel Oncology Center (1968–1988)

Eighty-four patients with testicular seminoma were treated at the Northern Israel Oncology Center during the years 1968–1988. Using the staging classification of Hussey, 69 patients (82%) had Stage I, eight (10%) had Stage IIA, four (5%) had Stage IIB, one (1%) had Stage IIIA, and two (2%) had Stage IIIB disease. Sixtynine patients (82%) had classic pure seminoma, nine (11%) had anaplastic seminoma and six (7%) had spermatocytic seminoma. Seventy-four patients (88%) underwent high inguinal orchiectomy and ten (12%) had a scrotal approach. Seventy-five patients (85%) were treated with postoperative irradiation. Stage I patients received 26–30 Gy to the paraaortic and ipsilateral pelvic lymph nodes. Stage IIA patients were treated in the same manner with a boost to the involved lymph nodes. With a mean follow-up of 97 months, 65 patients (77%) are alive and well with no evidence of disease, 7 patients (8%) are dead due to disease progression. The 5-, 10-, 15-, and 20-year actuarial survival for all patients was 90%, and for early stage patients 94%. Eight patients (14%) relapsed; 3 of them were salvaged by chemotherapy.Serious side effects of irradiation included lethal respiratory failure due to bleomycin-induced pulmonary fibrosis in one patient, peptic ulcer in three patients, hydronephrosis due to paraureteral fibrosis in one patient and recurrent paralytic ileus in one patient. Eight patients (10%) developed nine second cancers, three of them within the previous radiation field.It is concluded that appropriate planning and adequate radiation dose can yield a 20-year disease-free survival rate for more than 90% of patients with early stage testicular seminoma. Accurate staging may prevent overtreatment, thus reducting long-term toxicity. Because of the risk of developing a second primary cancer, careful follow-up monitoring with a high index of suspicion for such disorders is warranted.