The control of chronic lymphocytic leukemia with mediastinal irradiation.

Forty patients with chronic lymphocytic leukemia have been treated with mediastinal irradiation. A full remission was achieved in 18 (45 per cent) patients, a partial response in eight (20 per cent), "WBC control" in eight (20 per cent) and no response in 6 (15 per cent). Although mediastinal irradiation benefited all stages of disease, earlier stages of disease correlated with more complete and longer response to mediastinal irradiation. Toxicity was mild and transient and included leukopenia in five patients (12 per cent), thrombocytopenia in eight patients (20 per cent), mild esophagitis in 12 patients (30 per cent) and pneumonitis in four patients (10 per cent). There were no toxic deaths and mediastinal irradiation did not adversely effect survival. Treatment was readily given on an ambulatory basis and completed within four weeks. In five of 11 patients, abnormal immunoglobulins became normal. Eleven patients had abnormal lymphocyte transformation with PHA, five had marked improvement and three had partial improvements following mediastinal irradiation. This improvement appeared to correlate with response and survival but further study is necessary to confirm this relationship. Although most patients required additional therapy within two years, eight patients have required no further therapy for periods of twenty-eight months to thirteen years.

Metastatic carcinoma of the neck from an unknown primary.

From 1974 to 1984, 31 patients with metastatic carcinoma to the neck from an unknown primary were treated with radiation therapy. On review, three groups were identified based on presentation and treatment. Group I consists of 19 patients treated with curative intent. They all presented with cervical adenopathy, 11 patients with N1 disease, 2 with Stage N2A disease, 1 with Stage N2B disease, 4 with N3A disease, and 1 with unknown stage. The majority of patients were treated with portals encompassing the nasopharynx, oropharynx, hypopharynx, and neck to a dose of 5000 rad followed by boosts of 1000-1500 rad. The overall 2-year NED survival in this group was 63% (12/19). The most significant prognostic factor was the stage of the metastatic nodes. The NED survival rate for the 14 patients with Stage N1 and N2 was 86% (12/14). Histology of the lesions was not an important factor in the outcome. In Group II there are six patients who received palliative treatment because of large, fixed, cervical nodes. Three of these patients (50%) died within 2 months of completion of treatment. Group III consists of six patients who presented with supraclavicular adenopathy. All had persistent or recurrent disease within 19 months. We have concluded that in patients with metastatic carcinoma to the cervical nodes from an unknown primary, radiation therapy to the neck and suspected areas of primary disease may play an important role in cure, particularly in early stage disease.

Prostate cancer: comparison of retrograde urethrography and computed tomography in radiotherapy planning.

PURPOSE: To prospectively compare the role of retrograde urethrography and high-quality computed tomography during the treatment planning of patients with prostate cancer. METHODS AND MATERIALS: Forty consecutive men with localized prostate cancer underwent planning computed tomography prior to stimulation. At the time of simulation we performed retrograde urethrography and compared the location of the inferior border of the urogenital diaphragm to the location of the ischial tuberosities and the prostate and base of the penis as seen on the computed tomography scan. RESULTS: Interobserver identification of the prostatic apex varied in 70% of the cases. Perhaps due to this variability, attempts to place the inferior border of the treatment field in relation to the prostatic apex resulted in an inadequate margin (< 1 cm) beneath the urogenital diaphragm in 5%. In contrast, placing the inferior border at the ischial tuberosities or the base of the penis as seen on computed tomography insured an adequate margin for all patients. The distance from the urogenital diaphragm to the ischial tuberosities and, thus, the potential margin beneath the urogenital diaphragm was > 2 cm in 77%, while the distance from the urogenital diaphragm to the base of the penis was > or = 2 cm in only 43%. CONCLUSION: This demonstrates the difficulty in reliably identifying the prostate on computed tomography. Nevertheless, by identifying the base of the penis, planning computed tomography provides adequate information to cover the target volume, and results in minimal overtreatment of normal structures. Urethrograms are not necessary if the computed tomography is properly used or if the ischial tuberosities are used as a standard inferior border, but they can reduce the length of urethra in the treatment volume which could potentially reduce complications.

Role of intracavitary cuff boost after adjuvant external irradiation in early endometrial carcinoma.

Management of early endometrial carcinoma often consists of surgicopathologic staging followed by adjuvant radiation therapy (RT) for patients at risk of local recurrence. While an intracavitary vaginal cuff boost (VCB) is commonly given after external beam radiation therapy, its effects on local control and complication rates are unknown. To assess these effects, we reviewed 157 patients with FIGO Stage I (n = 134) or incidentally diagnosed (n = 23) endometrial adenocarcinomas. After surgery and external radiation therapy, 103 patients (65.6%) received a vaginal cuff boost of 3000-5000 cGy surface dose (Group I) and 54 (34.4%) did not (Group II). One hundred and two Group I and 52 Group II patients were evaluable for analysis. Median follow-up was 78.0 months for Group I and 60.0 months for Group II. Despite a preponderance of poor prognostic factors in Group II, no significant difference in local failure was seen. A component of local failure was seen in 6 Group I patients (6.0%) and 4 Group II patients (7.7%), p = 0.74. Distant failure, reflecting more advanced disease, was higher in Group II (19.2%) than in Group I (9.0%). Late complications included rectal bleeding/proctitis in 18.6% of Group I patients and 3.8% of Group II patients (p = 0.01). Overall, grade 2 complications occurred in 27.5% and 15.4% of Group I and II patients, respectively (p = 0.09). No difference in frequency of grade 3 complications was evident. Based on this retrospective study, intracavitary vaginal cuff boost after surgery and postoperative external beam radiation therapy does not appear to improve local control in early endometrial adenocarcinoma. Its possible effect on complication rates is uncertain.

Definitive radiotherapy for early glottic carcinoma: prognostic factors and implications for treatment.

PURPOSE: Treatment and disease-related factors were analyzed for their influence on the outcome of patients treated definitively with irradiation (RT) for early glottic carcinoma. METHODS AND MATERIALS: One hundred two patients with stage T1 or T2 glottic carcinomas were treated definitively with RT from December 1983 through September 1993. Median follow-up time was 63 months. Factors analyzed for each patient included age, sex, stage, anterior commissure involvement, surgical alternative, histologic differentiation, field size, total dose, fraction size, and total treatment time. Survival analysis methods were employed to assess the effects of these factors on local control and complication rates. RESULTS: The 5-year local control rates by stage were as follows: T1a, 92%; T1b, 80%; T2a, 94%; and T2b, 23%. By univariate analysis, factors found to have a significant impact on local control were stage, surgical alternative, fraction size, anterior commissure involvement, and overall treatment time. By multivariate analysis, stage, field size, and fraction size were the only significant factors that independently influenced local control. CONCLUSIONS: The inferior control rate for stage T2b lesions has implications for treatment. Our study supports the conclusions of reports in the literature showing that low fraction size negatively influences outcome in patients with early glottic cancer.

Definitive radiotherapy for early glottic carcinoma: prognostic factors and implications for treatment.

PURPOSE: Treatment and disease-related factors were analyzed for their influence on the outcome of patients treated definitively with irradiation (RT) for early glottic carcinoma. METHODS AND MATERIALS: One hundred two patients with stage T1 or T2 glottic carcinomas were treated definitively with RT from December 1983 through September 1993. Median follow-up time was 63 months. Factors analyzed for each patient included age, sex, stage, anterior commissure involvement, surgical alternative, histologic differentiation, field size, total dose, fraction size, and total treatment time. Survival analysis methods were employed to assess the effects of these factors on local control and complication rates. RESULTS: The 5-year local control rates by stage were as follows: T1a, 92%; T1b, 80%; T2a, 94%; and T2b, 23%. By univariate analysis, factors found to have a significant impact on local control were stage, surgical alternative, fraction size, anterior commissure involvement, and overall treatment time. By multivariate analysis, stage, field size, and fraction size were the only significant factors that independently influenced local control. CONCLUSION: The inferior control rate for stage T2b lesions has implications for treatment. Our study supports the conclusion of reports in the literature showing that low fraction size negatively influences outcome in patients with early glottic cancer.

Distinguishing tumor recurrence from irradiation sequelae with positron emission tomography in patients treated for larynx cancer.

PURPOSE: Distinguishing persistent or recurrent tumor from postradiation edema, or soft tissue/cartilage necrosis in patients treated for carcinoma of the larynx can be difficult. Because recurrent tumor is often submucosal, multiple deep biopsies may be necessary before a diagnosis can be established. Positron emission tomography with 18F-2fluoro-2deoxyglucose (FDG) was studied for its ability to aid in this problem. METHODS AND MATERIALS: Positron emission tomography (18FDG) scans were performed on 11 patients who were suspected of having persistent or recurrent tumor after radiation treatment for carcinoma of the larynx. Patients underwent thorough history and physical examinations, scans with computerized tomography, and pathologic evaluation when indicated. Standard uptake values were used to quantitate the FDG uptake in the larynx. RESULTS: The time between completion of radiation treatment and positron emission tomography examination ranged from 2 to 26 months with a median of 6 months. Ten patients underwent computed tomography (CT) of the larynx, which revealed edema of the larynx (six patients), glottic mass (four patients), and cervical nodes (one patient). Positron emission tomography scans revealed increased FDG uptake in the larynx in five patients and laryngectomy confirmed the presence of carcinoma in these patients. Five patients had positron emission tomography results consistent with normal tissue changes in the larynx, and one patient had increased FDG uptake in neck nodes. This patient underwent laryngectomy, and no cancer was found in the primary site, but nodes were pathologically positive. One patient had slightly elevated FDG uptake and negative biopsy results. The remaining patients have been followed for 11 to 14 months since their positron emission studies and their examinations have remained stable. In patients without tumor, average standard uptake values of the larynx ranged from 2.4 to 4.7, and in patients with tumor, the range was 4.9 to 10.7. CONCLUSION: Positron emission tomography with labeled FDG appears to be useful in distinguishing benign from malignant changes in the larynx after radiation treatment. This noninvasive technique may be preferable to biopsy, which could traumatize radiation-damaged tissues and precipitate necrosis.

Immunologic characterization of herpes simplex virus type 2 antigens ICP10 and ICSP11/12.

Infected cell protein 10 (ICP10) or antigen 4 (Ag4) and infected cell-specific protein 11/12 (ICSP11/12) have been suggested as specific antigenic markers for cervical carcinoma. Experiments were designed to determine whether ICP10 and ICSP11/12 are distinct antigens and to determine the cellular localization of ICP10. Results indicate that an apparent 160 kdalton (kDa) protein analyzed by 8.5% polyacrylamide gels (= 144 kDa protein analyzed by 7.0% polyacrylamide gels) was detected in HSV-2-infected but not mock-infected extracts. This protein is an early virus-induced protein appearing 2-4 h after HSV-2 infection, and it was synthesized in the presence of successive blocks with cycloheximide and actinomycin D. These properties are characteristic for ICP10 (Ag4), thus establishing the identity of the 160 kDa/144 kDa protein as ICP10. Furthermore, Western blot analyses indicated that ICP10 and ICSP11/12 are distinct antigens recognized by antibodies in sera from immune rabbit or human cervical carcinoma patients. In addition, monoclonal antibodies to the HSV-2-induced ribonucleotide reductase were reactive with ICP10. Antibodies in sera from rabbits immunized against ICP10 and monoclonal antibodies to the HSV-2-induced ribonucleotide reductase were reactive with antigens on the plasma membrane surface of HSV-2-infected cells. Also, the reactivity of monoclonal antibodies with these antigens was blocked by the rabbit antibodies based on immunofluorescence analyses. These data provide evidence that ICP10 is antigenically distinct from ICSP11/12, and that ICP10 is present on the plasma membrane of HSV-2-infected cells. Also, our data confirm and extend the tentative identification of ICP10 with the HSV-2-induced ribonucleotide reductase recently suggested by Bacchetti et al. (J. Virol. 49, 591-593, 1984).

Proton NMR relaxation times in the peripheral blood of cancer patients.

The proton spin lattice relaxation time (T1) of serum and leucocytes of cancer patients and normal volunteers was measured using pulsed NMR techniques. There was no statistically significant difference in the serum T1 values of cancer patients relative to normal. An increase in T1 relative to normal values was detected in the white blood cells of patients with active leukaemia. In these patients T1 fell to normal levels after the initiation of treatment. The variation of leucocyte T1 with the course of the disease for five patients having leukaemia is presented.