Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

PURPOSE: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. METHODS AND MATERIALS: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m2 i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). RESULTS: Amifostine administration was associated with a reduced incidence of Grade > or =2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. CONCLUSIONS: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival.     

Radiation Therapy and Simultaneous Chemotherapy for Recurrent Cervical Carcinoma

Purpose: To evaluate the efficacy and toxicity in patients with recurrence of cervical cancer treated with radiotherapy and simultaneous chemotherapy.Patients and Methods: Between 1987 and 2001, 24 patients with recurrent cervical carcinoma were treated with concurrent chemoradiotherapy. Nine patients had incomplete tumor resection prior to radiation therapy. Irradiation was delivered to a total dose of 60 Gy, in three patients with central recurrences supplemented by brachytherapy. One patient was treated with brachytherapy alone. Simultaneous chemotherapy was done as a combined therapy of 5-fluorouracil-(5-FU, 600 mg/m²/d1–5, 29–33) and cisplatin (20 mg/m²/d1–5, 29–33; 16/24 patients) or of 5-FU (1,000 mg/m²/d1–5, 29–33) and mitomycin C (10 mg/m²/d2, 30; 1/24 patients). Cisplatin alone (25 mg/m²/d1–5) and carboplatin alone (800 mg/m²/d1–5) were administered in 5/24 patients (21%) and 2/24 patients (8%).Results: The 5-year local recurrence-free survival rate was 37%, disease-free survival 33%, and overall survival 34%. Grade 3 toxicity (NCI-CTC grade 3) occurred mainly as diarrhea (38%), leukopenia (33%), and nausea (21%). Severe toxicity (grade 4) was not seen in any of the patients.Conclusion: Radiation therapy with simultaneous chemotherapy for recurrences of cervical cancer is an effective treatment with acceptable toxicity.     

Vacuum Application Increases Therapeutic Safety and Allows Intensified Local Radiation Treatment of Malignant Soft-Tissue Tumors

Purpose: In order to simplify and improve outcome of radiation therapy and final defect coverage in patients suffering from invasive soft-tissue tumors, brachytherapy and application of V.A.C.uum-assisted closure (V.A.C.^®) were combined with delaying flap incision. Patients and Methods: Two patients were excised as radically as possible and brachytherapy tubes were implanted directly on the tumor bed. At the same time, flaps for later defect coverage were preconditioned by circumcision. Brachytherapy and external- beam irradiation were performed directly on the vacuum sponge followed by subsequent defect coverage with the preconditioned flaps. Results: Excision significantly reduced tumor masses in both patients; in one case sensible and motor function of the involved extremity was clearly improved. V.A.C.^® coverage allowed repeated brachytherapy and external-beam applications following exact placing of plastic tubes and FLABs on the tumor bed. Sequential irradiation had no effect on neighboring flap tissues, which healed without impairment following transposition. Conclusion: Combination of V.A.C.^® and brachytherapy can effectively replace circumstantial and laborious IORT (intraoperative radiotherapy) procedures. Exact placement of tubes on the tumor bed without subsequent tissue coverage is conserving preconditioned flap tissues, which are transposed for final defect coverage at the end of radiotherapy. However, by circumventing radiation exposure of these tissues, a possible later irradiation sequence can be performed without endangering defect-covering flaps.     

Hypoxic Versus Normoxic External-Beam Irradiation of Cervical Carcinoma Combined with Californium-252 Neutron Brachytherapy

Purpose: The article focuses on the treatment and protective effects of hypoxyradiotherapy during external-beam irradiation of cervical carcinoma, including paraaortic lymph nodes, combining radiotherapy with californium-252 (²⁵²Cf) neutron brachytherapy. An analysis of treatment results, early and late side effects and complications is presented. Patients and Methods: From January 1989 to May 1997, 307 women with stage IIb and IIIb cervical carcinoma, treated with ²⁵²Cf neutron brachytherapy, were randomly divided into two groups and treated with external-beam irradiation to the paraaortic lymph nodes as follows: 155 patients (59 with stage IIb, 96 with stage IIIb) were treated by external-beam irradiation administered as a 60-Gy dose applied under conditions of acute hypoxia; 77 patients (30 with stage IIb and 47 with stage IIIb) received extended-field irradiation up to L4 and 78 patients (29 with stage IIb and 49 with stage IIIb) up to T12. 152 patients (58 with stage IIb, 94 with stage IIIb) were treated by external-beam irradiation administered as a 40-Gy dose applied under normal oxygenation conditions. 73 patients (29 with stage IIb and 44 with stage IIIb) received extended-field irradiaton up to L4 and 79 patients (29 with stage IIb and 50 with stage IIIb) up to T12. The same 56 Gy-equivalent (eq) doses at point A and 19 Gy-eq doses at point B were applied intracavitarily in both groups. The total radiation doses at points A and B were 99 and 79 Gy-eq, respectively, for patients treated with external-beam irradiation to 60 Gy under conditions of acute hypoxia. For patients treated with external-beam irradiation to 40 Gy under normal oxygenation conditions, the doses at points A and B were 85 and 59 Gy-eq, respectively. Results: The 5-year overall survival rate for all patients (stages IIb and IIIb) was 7.0% better for patients treated in acute hypoxia than for patients treated under normal oxygenation conditions (78.7% vs. 71.7% [p < 0.16]). The 5-year metastases-free survival rate was better by 11.7% for stage IIIb patients in the hypoxyradiotherapy group with extended field up to T12 as compared to patients with extended field up to L4 (97.4% vs. 85.7% [p < 0.05]). Comparison of metastases-free survival rate of stage IIIb patients after external-beam irradiation with extended field up to T12 in hypoxic condition versus normoxic condition showed a 12% better result for patients in hypoxic condition (97.4% vs. 85.4% [p < 0.04]). Occurrences of symptomatic radiation-induced reactions during or shortly after irradiation were more frequently observed in patients treated with a lower dose under normoxic conditions. During the period of 6-12 years after treatment there were no changes in the frequencies of occurrences of late effects and complications. Conclusion: The importance of the protective effects of hypoxyradiotherapy for dose escalation in external-beam irradiation of cervical carcinoma, including paraaortic lymph nodes, with regard to an improvement of the cure rates of metastases in paraaortic lymph nodes has been confirmed.     

Proteins of herpesvirus type 2. II. Studies demonstrating a correlation between a tumor-associated antigen (AG-4) and a virion protein.

Antigen AG-4, a HSV-2 antigen associated with actively growing squamous cervical tumors, correlates with infected cell protein number 10 (ICP 10), a minor component of the HSV-2 virion. This association is based on the following evidence: (i) There is a positive correlation between the amounts of AG-4 and ICP 10 produced at various times following sequential treatment of infected cells with cycloheximide and actinomycin-D; (ii) the passage history of HSV-2 affects the synthesis of AG-4 and ICP 10 in a similar manner; their synthesis is unaffected by the cell type; (iii) ICP 10 is precipitated by AG-4 positive but not by AG-4 negative sera; and (iv) following partial biochemical purification of crude AG-4 preparations, those fractions containing the AG-4 complement-fixing activity differ from those without this activity in that they contain ICP 10.     

Priming of immunological memory by pneumococcal conjugate vaccine in children unresponsive to 23-valent polysaccharide pneumococcal vaccine

Pneumococcal polysaccharide vaccine (PPV) is of limited immunogenicity in infants and immunocompromised patients. Our prospective randomized controlled trial investigated whether priming with pneumococcal conjugate vaccine (PCV) induced specific immunological memory in previously nonresponders to PPV. Of a total of 33 children (2 to 18 years) with polysaccharide-specific immunodeficiency (PSI), group A (n = 16) received two doses of 7-valent PCV in a 4- to 6-week interval, and a booster dose of 23-valent PPV after one year. Group B (n = 17) received two doses of PPV in a 1-year interval exclusively. Specific antibody concentrations for serotypes 4, 5, 6B, 9V, 14, 18C, 19F, and 23F were determined (enzyme-linked immunosorbent assay) before and at 7 and 28 days after administration of the PPV booster and compared to an opsonophagocytosis assay. Of group A, 64 to 100% had antibody concentrations of > or = 1 microg/ml on day 28 after the booster versus 25 to 94% of group B. Group A had significantly higher antibody concentrations for all PCV-containing serotypes already on day 7, indicating early memory response. Antibody concentrations were in accordance with functional opsonic activity, although opsonic titers varied among individuals. Pneumococcal vaccination was well tolerated. The incidence of airway infections was reduced after priming with PCV (10/year for group A versus 15/year for group B). Following a PPV booster, even patients primarily not responding to PPV showed a rapid and more pronounced memory response after priming with PCV.     

Synthesis of new polymers involving deltahedral carborane units

Aminocarboranes nido-7-NH₃⁺-(7-CB₁₀H₁₂)^? and closo-1-NH₃⁺-(CB₁₁H₁₁)^? were copolymerized with α,ω-dihalogenoalkanes to high-molecular-weight alternating copolymers. The nido-compound copolymer was crosslinked by means of sandwiching two open cages with Co^III ion yielding bis(monocarbollide)-cobaltate(III) units as the new type knot points. Metallacarboranes, 1,1′-diaminobis(monocarbollide)nickelate(IV) and two bridged bis(dicarbollide)cobaltates(III) (8,8′-μ-imino- and 8,8′-μ-oxyimino-), have provided hemipolymers of molecular weight up to a few thousands in the same type of copolymerization. A new methacrylic-type monomer was prepared by reaction of glycidyl methacrylate with 8,8′-(μ-imino)-(1,2-C₂B₉H₁₀)-3-Co^III and copolymerized with methyl methacrylate to high-molecular-weight statistical copolymers.