Seung Shin Hahn

Primary central nervous system germ cell tumors. Effect of histologic confirmation on radiotherapy.

Primary malignant intracranial germ cell tumors are rare lesions responsible for only 0.5% of all central nervous system (CNS) malignancy. With stereotactic localization these lesions can be safely biopsied, and histologic confirmation will affect the ultimate prognosis. This report is a multi‐institutional retrospective analysis of 33 patients diagnosed with a primary CNS germ cell tumor. Tumors in 14 patients (42%) were histologically confirmed (13 germinoma and one embryonal cell carcinoma); 19 patients were treated with a presumptive diagnosis. All patients were irradiated with a dose range of 3950 cGy to 6000 cGy to the primary lesions. Eight patients received craniospinal irradiation, and 25 patients were locally treated. The 5‐year actuarial survival for the entire population was 64%. The survival rate in patients with histologic confirmation was 79% versus 53% in the unbiopsied population. Radiation doses greater than 5000 cGy, radiotherapy volume, and age were prognostic factors in determining survival.

Radiotherapeutic management of cancer of the supraglottis

One hundred eighty‐five patients with cancer of the supraglottis were treated with curative intent by radiotherapy alone or combined with surgery over a 14‐year period. Minimum follow‐up was 3 years. Sixty‐eight percent had Stage III or IV disease. Moderate‐dose radiotherapywith surgery in reservewas the policy for the early lesionsand yielded a 3‐year locoregional control rate of 76% for T1 N0/N1T2 N0/N1and T3 N0/N1 lesions combined. In this group84% of patients with locoregional control retained laryngeal function. The major complication rate was 4%. Patients with advanced disease were treated with preoperative radiotherapy and surgeryresulting in an overall 3‐year no evidence of disease rate of 72%. Adverse prognostic factors in supraglottic cancer were the extent of the primary lesion and the presence of N2 or N3 nodes. Neither vocal cord fixation nor N1 nodes had a negative influence on survival in T3 and T4 disease.

Definitive Radiotherapy in the Management of Stage I and II Carcinomas of the Glottis

Definitive radiotherapy for early glottic carcinoma continues to offer excellent control and the advantage of voice preservation. In the 13 years from January 1972 through December 1984, there were 187 patients diagnosed with squamous cell carcinoma of the glottis at the University of Virginia Medical Center. One hundred forty-eight patients were treated with definitive radiotherapy as the initial management. The 3-year disease-free survival for the irradiated population was 93.6% in stage I and 75.5% in stage II. Twenty patients had recurrences following radiotherapy, and 13 of 20 were successfully surgically salvaged for an overall determinate survival of 100% in stage I and 85.7% in stage II at 3 years. These statistics are comparable to those from our previous 16-year review of 147 patients from 1956 through 1971. Factors of prognostic significance were persistent hoarseness after radiotherapy, impaired cord mobility, subglottic extension, and multiple sites of involvement in stage I. We conclude that definitive radiotherapy offers excellent survival and that a majority of the small number of treatment failures can be managed with surgical salvage.

Carcinoma of the middle ear and external auditory canal

Thirty-one patients with malignant tumors of the middle ear and external auditory canal (EAC) were observed at the University of Virginia Hospital from 1956 through 1980. Of 27 patients with carcinoma, 21 had squamous cell carcinoma, 4 had basal cell carcinoma and 2 had adenoid cystic carcinoma. One Ewings sarcoma and 3 rhabdomyosarcomas occurred in an age group of one to 10 years. The 27 patients with carcinoma are reviewed with regard to clinical presentation, treatment modality, results and complications. The majority (67%) of patients had a history of chronic ear drainage, 22% had a previous mastoidectomy or polypectomy and 7% had an associated cholesteatoma. The treatment modalities employed depended on the extent of disease and the patients general condition. Eighty percent of patients with carcinoma limited to EAC were alive and well at 5 years, compared to 43% of patients with involvement of the middle ear. Fifty-six percent of patients without invasion of the petrous bone were alive at 5 years compared to only 20% of patients with petrous bone involvement. The data strongly suggest that survival depends on the extent of disease. The corrected disease free 5 year survival rates were 14% for patients who had surgery alone and 50% for those who had surgery and radiotherapy. Of the three patients with advanced disease who received radiotherapy alone, none survived five years. Surgery or radiotherapy alone is not sufficient for most of the cases of carcinoma of the middle ear, since these patients often present with advanced disease. We recommend combined therapy, especially postoperative radiotherapy, except for early lesions that do not involve the mastoid or petrous bone. Other series suggest radiotherapy would be adequate and more effective than surgery for early lesions. Surgery will provide the diagnosis, determine the extent of disease, offer adequate drainage of infected material and relieve most pain before radiation therapy.

The prognostic significance of lymph node involvement in pyriform sinus and supraglottic cancers

Three hundred and thirty-three patients with carcinoma of the pyriform sinus or supraglottis were reviewed with regard to lymph node involvement and prognosis. All patients were treated with curative intent and had a minimum follow-up of 3 years. Every patient was restaged according to the AJCC, 1983 recommendations. In addition, nodal fixation to cervical fascia or muscle was evaluated with regard to prognosis. Seventy-five percent (89/119) of the pyriform sinus cancer and 47% (101/214) of the supraglottic cancer patients presented with clinically palpable cervical nodes. The distribution of patients according to N stage was 143 (43%), 84 (25%), 58 (17%), 48 (14%) for N0, N1, N2, N3 respectively. In patients where information on nodal fixation was available, 29% had fixed nodes. No difference in prognosis was noted between N0 and N1 or N2 and N3 stages, and these groups were therefore combined. The 3-year survival was 85% for T1 (N0/N1), 77% for T2 (N0/N1), 63% for T3 (N0/N1), and 65% for T4 (N0/N1) cases compared to 19% for T1 (N2/N3), 34% for T2 (N2/N3), 33% for T3 (N2/N3), and 32% for T4 (N2/N3) cases demonstrating that N stage predominates over T stage with respect to survival. Both the local recurrences and distant metastases increased as N stage advanced. A noteworthy difference between patients with fixed nodes and mobile nodes was found with regard to neck recurrence (35% versus 17%), distant metastases (33% versus 19%) and survival (27% versus 58%). In conclusion, nodal stage is a highly significant determinant of survival independent of T stage in cancers of the pyriform sinus and supraglottis. N0, N1 status and mobility were predictive of a favorable prognosis as opposed to N2, N3 status and fixation. These findings were consistent when the pyriform sinus cancers and supraglottic cancers were analyzed separately.

Results of the radiotherapeutic management of carcinoma of the cervix with emphasis on the influence of histologic classification

The histology of 365 of 396 patients (92%) treated with radiation therapy at the University of Virginia from 1968 to 1978 has been reviewed. Staging and treatment policies were consistent throughout this period, and have enabled the influence of histologic classification on treatment results to be evaluated. Large cell nonkeratinizing carcinoma (LCNK) was the most common type, 69%; followed by keratinizing (KSCC), 13%; and adenocarcinoma, 6.6%. Other varieties included adenosquamous, 3.6%; small cell undifferentiated carcinoma, 2.7%; papillary squamous, 1.6%; and glassy cell, 1.4%. Overall survivals by stage were similar to those reported from other centers. When examined by histologic type, the 5‐year survival rates ranged from 64% for adenosquamous to 13% for small cell. The most common varieties, LCNK and KSCC, had survival rates of 61% and 40% (P = 0.008). Considering both stage and histologic type, the differences between LCNK and KSCC persisted and were significant for Stage IIB (P = 0.023). Of particular interest are the poor results in small cell carcinoma and adenocarcinoma, except in the earliest stages, and the good results for adenosquamous carcinoma. The patterns of failure by histologic type showed that local failures were higher in cases of KSCC than in LCNK, indicating a probable difference in radiosensitivity. Distant spread was similar for both types. Both small cell carcinoma and adenocarcinoma showed high rates of distant spread and local failure except in the early stages. Considering survival and failure rates, three prognostic groups could be identified. In descending order of curability these were: 1( LCNK and adenosquamous carcinoma; 2) KSCC, papillary squamous carcinoma, and adenocarcinoma; and 3) small cell carcinoma and glassy cell carcinoma.

A phase I-II trial of multimodality management of bulky gynecologic malignancy: Combined chemoradiosensitization and radiotherapy

Between December 1983 and December 1987, there were 44 patients with bulky, nonresectable squamous cell carcinomas of the gynecologic tract (cervix, 36; vagina, eight) who were treated with concomitant chemotherapy and radiotherapy. Chemotherapy consisted of 5‐fluorouracil (5‐FU) 1 g/m2 given by continuous intravenous infusion on days 1 through 4 and mitomycin C 10 mg/m2 given intravenously on day 1. External‐beam irradiation was started on day 1 with a total calculated dose of 5000 cGy in 25 fractions employed. This was followed by brachytherapy. With a mean follow‐up of 30.3 months and a median of 28 months, local control has been achieved in 32 of 44 patients (73%). The overall response rate was 88% (3‐month partial response, 43%; 3‐month complete response, 45%; 8‐month partial response, 15%; 8‐month complete response, 73%). Analysis of complications by Radiation Therapy Oncology Group (RTOG) criteria did not demonstrate an increase in acute or late complications.

Primary malignant extragonadal germ cell tumors. An analysis of the effect of radiotherapy

A retrospective analysis was performed on all patients diagnosed with biopsy‐proven extragonadal germ cell tumors at the University of Virginia (Charlottesville, VA), The Medical University of South Carolina (Charleston, SC), the Bethesda Naval Hospital (Bethesda MD. ), and The Medical College of Virginia (Richmond, VA) for the time period of January 1965 to December 1984. A total of 54 patients were treated with the initial sites of presentation observed: mediastinum, 26; central nervous system, 14; retroperitoneum, eight; and sacrococcygeal region, six. Megavoltage irradiation was used in 44 patients with a dose range of 2400 to 5580 cGy (mean, 4213 cGy). With a minimum follow‐up of 4.0 years and a mean follow‐up of 10.8 years, the 5‐year actuarial survival for the entire population was 57.8%. Local control was achieved in 26 of 44 (59%) of the irradiated population. Factors of prognostic significance included histologic type at presentation, site of presentation, and radiation doses greater than or equal to 4000 cGy. Radiotherapy appears to be an effective modality in patients with extragonadal seminomas; however, the non‐seminomatous tumors do not appear to be as radioresponsiye.

The effectiveness of treatment of lymph nodes in cancers of the pyriform sinus and supraglottis

Three hundred and twelve patients with pyriform sinus or supraglottic cancer were reviewed with respect to effectiveness of therapy upon nodal control. All patients had a minimum 3-year follow-up. Combined modality therapy (radiotherapy and surgery) conferred a higher neck control rate for both N0/N1 and N2/N3 nodes than moderate dose (50 to 60 Gy) radiotherapy alone. Neck dissection appeared to be a significant component of therapy for all neck stages. Fixed nodes, a subset of N2/N3 disease with a very poor prognosis, required combined modality therapy for the best nodal control rates. Downstaging to pN0 with preoperative radiotherapy provided superior nodal control and survival rates.

Uncommon variants of cervical carcinoma treated with radical irradiation: a clinicopathologic study of 66 cases

Although certain histologic types are uncommon in cervical carcinoma, these tumors as a group comprise almost one in five patients. The present study throws some light on the therapeutic approaches that are appropriate. From 1968 through 1978, 396 patients with carcinoma of the cervix were treated primarily with radiation therapy, at the University of Virginia Medical Center. The treatment policy remained consistent throughout the study interval. Diagnostic pathologic material was reviewed and uniformly classified in 365 cases (92.2%). Over 80% were invasive keratinizing or nonkeratinizing squamous cell carcinoma. There were 66 patients with uncommon histologic types including 24 adenocarcinomas (6.6%), 13 adenosquamous carcinomas (3.6%), 10 small cell carcinomas (2.7%), 6 papillary squamous carcinomas (1.6%), 5 glassy cell carcinomas (1.4%), and 8 miscellaneous types (2.2%). These 66 patients form the basis for this report. Five‐year survival rates and causes of failure are presented along with management recommendations.