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.

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.

Positron emission tomography of patients with head and neck carcinoma before and after high dose irradiation.

BACKGROUND: Positron emission tomography (PET) with labeled fluorodeoxyglucose (FDG) demonstrates increased tracer uptake in many neoplasms. This study was undertaken to define the patterns of FDG uptake in head and neck neoplasms before and after high dose irradiation. METHODS: Twenty-five patients were evaluated prospectively with PET and standard clinical and radiographic techniques before and after irradiation. RESULTS: Twenty-seven primary sites were confirmed pathologically in 23 patients and included the nasopharynx (four lesions), oropharynx (14 lesions), larynx (five lesions), oral cavity (two lesions), and paranasal sinuses (two lesions). Two patients had unknown primary sites. Twenty-four of 27 primary sites correlated with areas of increased tracer uptake on PET scans. Five patients had increased uptake in cervical lymph nodes that were uninvolved by radiographic or clinical criteria. Positron emission tomography seemed to be able to differentiate tumor activity from fluid-filled sinuses in two patients with paranasal sinus tumors. In two patients with unknown primary sites, increased uptake in the base of tongue after PET suggested occult primary sites. Positron emission tomography scans obtained 1 month after high dose irradiation (RT) indicated decreased levels of FDG uptake in all patients' tumors. However, these scans did not accurately reflect the status of disease in these patients. Scans obtained 4 months after RT were believed to assess more accurately the presence of malignancy. CONCLUSIONS: Positron emission tomography is a new modality that may be useful in defining tumor activity in clinically negative areas. Appropriately timed posttreatment PET may be useful in predicting outcome after definitive RT and in distinguishing viable tumors from normal tissue changes after RT in patients with head and neck carcinomas.

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.

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.

T1-T2 carcinoma of the glottis: relative hypofractionation.

Radiation therapy, the preferred primary treatment for early squamous cell carcinoma of the glottis, offers high local control rates with voice preservation; however, the optimal treatment schedule is subject to debate. Local control, with and without surgical salvage, and associated long-term effects and complications were retrospectively analyzed in 90 patients treated with definitive radiation therapy for T1-T2 squamous cell carcinoma of the glottis. Patients received three weekly fractions of 333 cGy to a total dose of 60 Gy in 6 weeks. Median follow-up was 51.5 months. With radiation therapy alone, local control was 92% for T1 disease and 88% for T2; with surgical salvage, the control rate was 99%. Long-term effects included moderate hoarseness (16% of patients) and moderate or severe laryngeal edema (10% of patients). In seven patients who underwent salvage surgery, the complication rate was 29%. Despite excellent local control, this regimen may produce more long-term effects and complications than conventional fractionation.

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.

Testicular seminoma: effectiveness of primary radiation therapy.

We retrospectively studied 44 patients with testicular seminoma treated with primary radiation therapy at the Bowman Gray School of Medicine from 1972 through 1982. The 26 patients with stage I disease received infradiaphragmatic irradiation. Eleven of the 12 with stage II disease, the three with stage III disease, and three with retroperitoneal disease received irradiation to the mediastinum and infradiaphragmatic area. The three-year survival rate without evidence of disease was 100% for stage I. For stage II, the rate was 92% with radiation therapy alone and 100% with salvage therapy. In two patients with stage III disease radiation therapy failed, but both had bulky abdominal disease. Only one died of seminoma. One of the patients with retroperitoneal tumor had unsuccessful radiation therapy but was salvaged with chemotherapy. Neither the diagnosis of anaplastic seminoma in nine patients nor elevated preorchiectomy beta-HCG levels in four patients affected their prognosis. In our series, primary radiation therapy with proper salvage therapy yielded 98% survival.

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.

Effects of tumor status on the regulation of natural killer cell activity by tumor-associated fetal antigens.

In the present study we examined the effects of a tumor-associated fetal antigen (TAFA-II) on the activity of natural killer (NK) cells isolated from human cancer patients. TAFA-II suppressed the NK cell response of some patients, and the level of suppression appeared to be independent of tumor type or stage of cancer therapy. No significant correlations were found between lymphocyte, neutrophil, monocyte, or eosinophil populations and TAFA-induced suppression of NK cell activity. TAFA-II effects were also not attributable to Ia+ cells or to OKT3, OKT4, or OKT8 positive cells. This work confirmed results obtained in the rat model, in which suppression appeared to be directly mediated on the NK cell.

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).

Results of radiotherapy for stage I and II Hodgkin's disease.

Fifty-six patients with pathologically staged I and II (A and B) Hodgkin's disease were treated with radiation therapy. Three-year relapse-free survival, total survival, and complications were analyzed. Chemotherapy was valuable as rescue treatment and as part of the initial treatment in patients with stage IIB disease. Complications were minimal.

Extraneural metastases from cerebellar medulloblastoma.

Six of 19 patients treated for medulloblastoma over an 8-year period developed extraneural metastases. The most common sites of metastatic disease were bone (5 patients), and bone marrow (4 patients). Radionucleotide bone scans and/or bone marrow aspirates detected disease in all such cases. Four patients also had recurrence within the central nervous system. Four of six patients relapsed within one year of initial treatment. All recurrences were treated with radiotherapy and/or chemotherapy with symptomatic improvement. The use of bone scans and bone marrow aspirations in the follow-up of patients with treated medulloblastoma would seem to be indicated.

Medulloblastoma: treatment results with radiation therapy.

The treatment results in 18 patients with medulloblastoma were reviewed retrospectively. All patients were treated postoperatively with simultaneous craniospinal irradiation. Forty-four percent of the total group were alive without evidence of disease. Six of the 12 patients eligible for analysis at three years after completion of treatment had continuous disease-free survival. Six patients with intracranial recurrence received a second course of whole-brain irradiation, and two of these are alive.

Relationship of lesion size to survival in patients with stage IB squamous cell carcinoma of the cervix uteri treated by radiation therapy.

Forty-five patients with Stage IB squamous cell carcinoma of the cervix uteri were treated with radiation therapy alone. The five year actuarial survival rate of the 22 patients in group 1 in whom the tumor was less than 4 centimeters in diameter was 95 per cent, which was significantly higher than the 67 per cent survival rate in the 23 patients in group 2 with bulky lesions greater than or equal to 4 centimeters in diameter, p less than 0.05. These results of radiation therapy are consistent with surgical results recently reported and indicate that patients with bulky lesions, especially those tumors greater than or equal to 4 centimeters in size, comprise a high risk subset within the Stage IB classification. A new classification is proposed in which bulky lesions are designated Stage IC, advanced overt, so that such high risk patients might be identified and more efficacious treatment regimens might be developed.

Efficacy of radionuclide scanning in patients with lung cancer.

Ninety-two patients with histologically proved carcinoma of the lung were studied retrospectively to determine the usefulness of liver, brain, and bone imaging in their examination and treatment. Occult metastatic liver disease was observed in two (5.3%) of 38 asymptomatic patients, while four (6.6%) of 58 neurologically intact patients had abnormal brain scans. Eight (13.6%) of 59 asymptomatic patients had metastatic bone disease. Seven (18.4%) of 38 patients with no clinical evidence of metastatic disease to liver, brain, or bone had at least one type of abnormal radionuclide study. More than half (52.5%) of the patients studied had at least one abnormal scan exclusive of symptoms. Radionuclide imaging is a useful procedure in the initial evaluation and subsequent management of lung cancer.