Edward Rosenblatt

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.

Total Skin Electron Irradiation: Efficacy in Early Mycosis Fungoides

The rare, indolent, but lethal malignancy, mycosis fungoides (MF), is amenable to durable remissions if treated topically at an early stage with nitrogen mustard, PUVA, or radiotherapy. A modification of conventional therapeutic irradiation which utilizes electron beams rather than photons, has been in use since 1951. This method, termed total skin electron irradiation (TSEI), has achieved consistently good CR rates (95-100%) at a variety of centres in the U.S.A., England, France, and Italy, despite troublesome differences in staging systems. In northern Israel we have treated 37 MF patients with TSEI during the past 13 years. All 21 of our early stage patients achieved CR, which is no longer regarded as an unusual result. However, most workers in the field acknowledge that issues of optimal dosing and curative potency remain unresolved.

LATE VISUAL AND AUDITORY TOXICITY OF RADIOTHERAPY FOR NASOPHARYNGEAL CARCINOMA

Aims and Background Classical irradiation of carcinoma of the nasopharynx involves large fields and high doses; therefore, significant late toxicity and late side effects are to be expected. Given the fact that nasopharyngeal carcinoma (NPC) is a relatively radiosensitive disease and a significant proportion of patients are long-term survivors, late visual and auditory complications of treatment are of utmost concern for patients and radiation oncologists. The aim of this study was to evaluate the long-term visual and auditory toxicity in patients treated with radiotherapy for NPC. Methods and Study Design Forty-three long-term survivors (including 11 children), following definitive radiotherapy for NPC, underwent a thorough visual and auditory evaluation 2–22 years after their treatment. Ophthalmological examination consisted of anamnesis of dry eye syndrome and visual acuity, visual acuity testing, slit-lamp examination, Schirmer test, fundus examination, and intraocular pressure measurement, as well as fluorescein angiography in patients with pathological vascular findings in the fundus examination. Audiological evaluation included anamnesis of hearing loss, tinnitus or vertigo, examination of the ears and nasopharynx, audiogram, and tympanogram. Results Radiation retinopathy was found in 16% of patients by fundus examination, with one patient (2.3%) developing blindness. Severe dry eye syndrome was present in 26%. Fifty-six percent had some degree of hearing impairment, with 74% showing severe sensorineural hearing loss. Fifty-eight percent of patients reported tinnitus and 26% reported suffering from dizziness. Radiation retinopathy as well as all manifestations of auditory toxicity were found to bear a direct correlation with dose per fraction. Conclusions Unless there is tumor involvement, the orbital contents should be completely excluded from the target volume. Auditory toxicity is significant when treating NPC with two-dimensional techniques.

Total Skin Electron Irradiation in Mycosis Fungoides Dose and Fractionation Considerations

This study was undertaken to analyze the influence of total skin dose and dose-fractionation schedules on the response rate, survival and skin toxicity of patients with mycosis fungoides [MF] treated with total skin electron irradiation [TSEI]. From 1979 to 1992, 40 patients with MF were treated with TSEI using a modified Christie Hospital technique. Mean follow-up time was 48 months [median 20 months]. 37/40 patients completed TSEI; three died due to non-treatment-related conditions during therapy. 34/37 [92%] treated patients achieved complete remission [CR] and 16/40 [40%] are alive with no evidence of disease. Over the years, changes in dose-fractionation schedules were made and correlated with the pattern of CR and skin toxicity. The 5-year actuarial survival [Stanford staging] was 84% in Stages IA-IB [all Stage IA patients are alive] and 59% in Stage II. The probability of survival of Stage III-IV patients was 30% at 30 months. Late skin toxicity was mild to moderate in 60% and severe in 25% of patients. A reduction of the total dose and dose-per-fraction resulted in an acceptable CR rate and a significantly lower toxicity. TSEI is effective in early stage MF. Skin control and late skin toxicity seem to be dose-fractionation-schedule related. For the early stages, the optimal treatment schedule seems to be 24-30 Gy to the whole skin surface in 2.4-3.0 Gy fractions, given twice weekly over a period of four to six weeks. Total doses of 24-30 Gy at 2.4-3.0 Gy per fraction yielded comparable skin control rates with lower skin toxicity.

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.

Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin

SummaryA total of 30 consecutive patients with refractory or relapsing non-Hodgkins lymphoma (NHL) were treated with a combination of dexamethasone, etoposide (VP-16), ifosfamide, and cisplatin (DVIP). In all, 9 subjects (30%) showed a partial response and 10 (33%) achieved a complete response (CR) lasting from 2.5 to 24+ months. Aggressive histology, no prior therapy with VP-16, a CR to previous chemotherapy, and a treatment-free interval of >6 months prior to the present study were associated with the high CR rate. DVIP caused pronounced myelosuppression (median granulocyte nadir and median platelet nadir, 380/mm3 and 73.000/mm3, respectively), but no drug-related death occurred. We conclude that DVIP is an effective salvage combination, especially in aggressive NHL, that produces acceptable toxicity.

Case Report: Malignant Thymoma Associated with Progressive Systemic Sclerosis

A 65-year-old man manifested certain features of scleroderma several years before discovery of malignant thymoma. Following tumor resection, the signs and symptoms of scleroderma did not improve, and the patient experienced the abrupt onset of renal failure with malignant hypertension 7 months after the operation. The scleroderma renal crisis caused terminal renal failure, which was treated by chronic hemodialysis. This is the second reported case of thymoma associated with progressive systemic sclerosis (PSS). The authors suggest that thymoma and various immunologic disorders have a common etiologic factor which has not yet been found. This case emphasizes that thymectomy frequently has little effect on the course of the immunologic disease. The implications of the association of thymoma and PSS are discussed.

High-Dose-Rate Endobronchial Brachytherapy in Endobronchial Metastatic Malignant Chondroid Syringoma

A 65-year-old man with malignant chondroid syringoma (MCS) was found to have pulmonary metastases in the form of multiple pulmonary nodules 4 years after wide excision and adjuvant radiotherapy of a primary abdominal wall tumor. Atelectasis of the lingula due to obstructive endobronchial metastasis, resistant to combination chemotherapy, led us to perform high-dose rate (HDR) endobronchial brachytherapy for the first time in this rare tumor with a favorable response. This case emphasizes the role of HDR brachytherapy as a palliative procedure in endobronchial tumors not responding to other treatment modalities, even those considered to be radioresistant.

Low dose-rate interstitial brachytherapy in soft tissue sarcomas

Purpose. To assess the effectiveness of Ir-192 interstitial brachytherapy as an adjunct to wide local excision as a functionsaving strategy for soft tissue sarcomas. Subjects and methods. From September 1993 to April 1998, 20 consecutive patients diagnosed with soft tissue sarcomas were treated with a combination of wide local excision and interstitial brachytherapy. In 16 patients brachytherapy was done as an intraoperative procedure, while in four, the implant was performed post-operatively under local anesthesia. Eleven of the 20 patients also received external beam radiotherapy following the implant. Results. After a mean follow-up of 27 months (4–54) the local control rate for all 20 patients was 85% (17/20). In the 16 patients who had an intra-operative implant, local control was 94% (15/16). In the four patients who underwent a post-operative implant, local control was 50% (2/4). Actuarial 5-year survival was 90%. There were three cases (15%) of severe local complications. Conclusions. Wide local excision followed by low dose rate intersitital brachytherapy have yielded a 85% local control rate in 20 patients with soft tissue sarcomas. Local control rates were higher when the implants were done as an intra-operative procedure than as a post-operative one.

Implementing a tantalum wire mesh to increase the skin dose in low-energy electron irradiation of the chest wall.

Radiation treatment of the post-mastectomy chest wall is performed in our institution by straight-on electron irradiation. The chest-wall thickness is measured and the beam energy is chosen so that the chest wall is treated to therapeutic doses, while sparing the underlying lung tissue. The most commonly chosen energies are 6 and 9 MeV. The skin dose should be 90% of the dose prescribed to the chest wall, which is higher than can be achieved with 6- and 9-MeV beams because of the low surface dose. The addition of a bolus slab during part of the treatment can correct for this; however, the added depth means that a higher energy has to be chosen, which will increase the lung dose (the higher the electron energy, the slower the falloff of the electron depth-dose curve). A mesh of a high-Z material above the skin gives rise to obliquely scattered and low-energy electrons that effectively spoil the buildup zone. Dosimetric measurements of a Tantalum (Ta) mesh were performed using a dose scanner in a water tank and a film inserted in a humanoid phantom during a simulated treatment. Measurements were also done for the clinically relevant cases of oblique beam incidence and with the mesh placed 1 cm above the surface. The measurements demonstrate the spoiling of the buildup zone, while having only a moderate influence on the dose distribution beyond the dose maximum. The mesh also changes the absolute dose. In a fractionated regime, the first part of the treatment would be without the mesh, adding it only during the latter fractions. The total dose distribution gives 90% to the skin, while leaving the depth-dose characteristics beyond the dose maximum virtually unchanged.