Total body irradiation for stage II-IV non-Hodgkin's lymphoma: ten-year follow-up.

Between 1972 and 1977, a prospective study was conducted at the University of Florida on the role of total body irradiation (TBI) in the management of stage II-IV non-Hodgkin's lymphoma (NHL). Forty-four consecutive de novo (DN) patients (including ten stage II, 18 stage III, and 16 stage IV), as well as 16 previously treated (PT) patients, were accrued. Twenty of the 44 DN patients were symptomatic at presentation. Complete clinical responses were obtained in 20 of the 27 DN patients with favorable histologies (FH), and six of the 17 with unfavorable histologies (UH). Partial responses were obtained in six patients with FH and 11 patients with UH; only one patient showed no response to TBI. By univariate analysis, PT patients showed a trend for decreased relapse-free survival (P = .066) and decreased survival (P = .093). Multivariate analysis identified the best predictors of response rate to be histology (P = .0146) and marrow involvement (P = .0854); of relapse-free survival, histology (P = .0035), and TBI dose (P = .002); and of absolute survival, age (P = .0012), histology (P = .012), and TBI dose (P = .029). Thirty of the 41 patients who relapsed underwent salvage treatment with either chemotherapy or radiation. Twenty-three of the 30 undergoing salvage therapy obtained a second complete clinical response. There were no treatment-related deaths. The most common complication was thrombocytopenia. The major late complications were myeloproliferative disorders in four patients, which occurred only after cumulative TBI doses in excess of 200 cGy.

Pulmonary function tests after whole-lung irradiation and doxorubicin in patients with osteogenic sarcoma.

PURPOSE: Because of the scarcity of information regarding long-term follow-up of pulmonary function after whole-lung irradiation, a prospective study was started at the University of Florida in 1979 to evaluate pulmonary function after treatment with whole-lung irradiation and doxorubicin in patients with osteogenic sarcoma. PATIENTS AND METHODS: Between 1979 and 1984, 57 osteogenic sarcoma patients with no evidence of metastatic disease at diagnosis received adjuvant therapy consisting of whole-lung irradiation (with the heart shielded) followed by Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH). The whole-lung irradiation schema was 1,600 cGy in 10 fractions with 8-MV x-rays via anterior and posterior fields. This was followed by five cycles of Adriamycin for a total dose of 450 mg/m2. Pulmonary function tests (PFTs) consisting of spirometry, lung volumes, and diffusing capacity were obtained before the whole-lung irradiation, at 6 and 12 months after irradiation, and at yearly intervals thereafter. RESULTS: At the time of analysis, 28 of the 57 patients were available for study, with a mean follow-up of 42 months (range, 6 to 77 months). Follow-up pulmonary function testing revealed decreased forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV1) during the first 6 to 12 months after whole-lung irradiation. These values returned to baseline during the second-year posttherapy and remained at baseline throughout the remainder of the follow-up period. Changes in lung volumes demonstrated a similar early trend, with significant decreases in total lung capacity (TLC) and functional residual capacity (FRC) at 6 to 12 months. These changes, however, did not improve significantly during the remainder of the follow-up period. Diffusing capacity of the lungs for carbon monoxide (DLCO) also reached a nadir at 6 to 12 months after whole-lung irradiation, with resolution by 2 years and maintenance of at least baseline values for the remainder of the follow-up period. CONCLUSIONS: Treatment with whole-lung irradiation and Adriamycin, as given in this study, caused no significant sequelae, as demonstrated by pulmonary function testing during the mean follow-up period of 42 months, although a mild, transient restrictive ventilatory defect occurred at 6 to 12 months after treatment.

Radiation treatment of carcinoma of the cervix.

To give the optimal treatment to each individual with cancer of the cervix, there must be very close cooperation and professional rapport between the radiation oncologist and gynecologic oncologist. Patients should be evaluated together with a review of the pertinent pathology and diagnostic roentgenograms in order to determine the optimal, individualized treatment plan for each patient. In the radiotherapeutic management of patients with cervical cancer, meticulous care must be taken in the treatment setups for external radiotherapy and the intracavitary radium applications. External fields should be carefully shaped to minimize the amount of normal tissue treated. Radium applications must be carefully reviewed with attention to and correction of minor deviations in the radium geometry, which could give rise to "hot" or "cold" spots in the radium dosage. With attention paid to the above factors, radiotherapy in the treatment of cervical cancer can be extremely rewarding. The majority of the patients treated will be cured and will be able to return to normal, functional lives. Most of the patients seen with cervical cancer do not have other major medical illnesses that will limit their lifespan, and as a result, 10-, 20-, and 30-yr survivals after treatment are being reported.

Planned preoperative irradiation in the management of clinical stage B2-C (T3) bladder carcinoma.

In recent years the role of planned preoperative irradiation in the management of clinical Stage B2-C (T3) bladder cancer has been questioned by a number of investigators. Much of the confusion regarding the efficacy of combined therapy results from studies that compare the results of treatment of pathological Stage B2-C patients treated by cystectomy alone versus clinical Stage B2-C patients treated by preoperative irradiation plus cystectomy. Such comparisons are biased because of (1) the exclusion of a large number of Stage D patients from cystectomy-alone series and their inclusion in preoperative irradiation plus cystectomy series and (2) the inclusion in the cystectomy-alone series of patients whose clinical stages were less than or equal to T2. The purpose of this paper is to compare the results of treatment in patients with clinical Stage B2-C bladder carcinoma following radical cystectomy alone versus preoperative irradiation plus cystectomy. This article reviews the rationale for administering preoperative irradiation, the effect of preoperative irradiation on the pathological specimen (including down-staging, the effect on regional lymph nodes, and radioresponsiveness according to tumor configuration, i.e., papillary vs. solid), the impact of preoperative irradiation on pelvic recurrence and 5-year survival, and the effect of preoperative irradiation on operative and postoperative complications. This paper cites all known literature on the subject in the English language. Data comparing 5-year survival results between radical cystectomy alone versus preoperative irradiation plus cystectomy are analyzed in three different ways: (a) retrospective comparisons of historical results, (b) review of the results of 6 randomized trials, and (c) comparison of concomitantly treated "modern-day" (1960-1980) series treated by either radical cystectomy alone versus preoperative irradiation plus cystectomy in 1185 patients. Preoperative results are also analyzed according to dose level (2000 rad versus 4000 rad versus 4500-5000 rad). The data presented indicate that the addition of preoperative irradiation to cystectomy for clinical Stage B2-C (T3) bladder cancer adds approximately 15 to 20 percentage points to the 5-year survival, leading to a survival figure that is approximately half-again that achieved by cystectomy alone.

The incidence of myelitis after irradiation of the cervical spinal cord.

To further define the tolerance of the cervical spinal cord, the dose of radiation to the cervical spinal cord was calculated for all 2901 patients with malignancies of the upper respiratory tract treated at the University of Florida between October 1964 and December 1987. To further define the population evaluated, certain criteria were used: (a) a minimum of 3000 cGy to at least 2 cm of cervical spinal cord and (b) a minimum of 1 year of follow-up, unless a neurological complication occurred before 1 year. A total of 1112 patients were evaluable, of which 2 (0.18%) developed radiation myelitis. One received 4658 cGy to the cervical cord at 172.5 cGy per day, and the other patient received 4907 cGy to the cord at 169.2 cGy per day. The risk of myelitis at each dose level was 0/124 at 3000-3999 cGy, 0/442 at 4000-4499 cGy, 2/471 at 4500-4999 cGy, and 0/75 at a cord dose of 5000 cGy or greater.

Elective neck irradiation for squamous cell carcinoma of the head and neck: analysis of time-dose factors and causes of failure.

This is an analysis of 190 patients who were treated with radiation therapy alone at the University of Florida, between October 1964 and December 1982, for T1-4 N0 squamous cell carcinoma of the head and neck; in all patients, the primary lesion was permanently controlled and the neck was evaluable for at least 2 years following radiation therapy. The control of neck node disease is analyzed as a function of elective neck irradiation, the dose of radiation delivered to the first-echelon lymph nodes, and the likelihood that occult disease was present in the neck prior to treatment.

Elective lower neck irradiation: 5000 cGy/25 fractions versus 4050 cGy/15 fractions.

This is an analysis of 171 patients treated with irradiation alone for squamous cell carcinoma of the head and neck who received elective radiation therapy to the clinically negative low neck. All patients have a minimum follow-up of 2 years and 63% have had at least 5 years of follow-up. Patients were excluded from this analysis if they developed recurrent disease at the primary site or in the upper neck. The majority of patients, 162/171, were treated with one of 2 dose-fractionation protocols: 5000 cGy/25 fractions (5 fractions per week for 5 weeks) and 4050 cGy/15 fractions (5 fractions per week for 3 weeks). Patients were subdivided into four risk groups based on the estimated likelihood of subclinical disease in the neck. There was no difference in the rate of the neck disease control between these 2 dose-fractionation protocols. We conclude that 5000 cGy/25 fractions and 4050 cGy/15 fractions are equally effective in sterilizing occult neck disease.

The influence of excisional or incisional biopsy of metastatic neck nodes on the management of head and neck cancer.

Between November 1964 and December 1981, 80 patients who had undergone an open biopsy of a cervical lymph node containing squamous cell carcinoma were treated with curative intent in the University of Florida Division of Radiation Therapy. Irradiation was the initial step in the definitive treatment of all patients, followed by neck dissection and/or primary resection, as indicated. The patients were divided into two groups. (a) NX (no gross residual neck disease) (25 patients): According to the referring surgeons' and pathologists' reports, a single, clinically positive lymph node was totally excised in 25 patients. No other clinically positive lymph nodes were appreciated upon referral. No neck dissections were added following irradiation in this group of patients. The absolute 5 year disease-free survival in the NX group was 79%, and the rate of neck disease control was 96%. (b) Gross residual neck disease (55 patients): Gross residual disease remained in the neck in 55 patients following biopsy. In some patients, only an incisional biopsy of a large mass had been performed; in others, only one of several involved nodes was removed. The absolute 5 year disease-free survival in this group of patients was 31%, and the rate of neck disease control was 64%. The more consistent addition of a neck dissection in recent years has resulted in improved neck control rates in this group: 13/20 (65%) for N1-N2 disease and 2/7 (29%) for N3A disease following irradiation alone versus 6/7 (86%) for N2 disease and 5/8 (63%) for N3A disease when a neck dissection was added following irradiation. There are some differences in the rates of neck control, control above the clavicles, survival, distant metastasis, and complications between this series and other reported series in which open neck-node biopsy preceded definitive treatment. Possible reasons for these differences are discussed.

Parotid area lymph node metastases from carcinoma of the skin.

From January 1966 through April 1980, 38 patients with squamous cell carcinoma and one patient with basal cell carcinoma of the skin with lymphatic metastases to the parotid area were treated with curative intent at the University of Florida. Fourteen were initially treated with surgery, nine inoperable patients were treated primarily with radiation therapy, and 16 were treated with planned combined therapy, i.e., superficial or total parotidectomies with preoperative or postoperative radiation therapy. The ultimate parotid area control rate for the group treated with radiation alone was 50%; there were no failures at doses above 6500 rad. The parotid area control rate was 88% in the combined-treatment group with no failures when the surgical margins of resection were free; however, when gross residual disease was left behind, only 4 of 6 lesions were controlled. In the surgery-alone group, the ultimate parotid area and neck control rate was only 15%. The major sequela from combined therapy was sacrifice of the seventh nerve at surgery. Treatment methods are discussed.

Reproducibility of mantle irradiation with daily imaging films.

Daily mantle imaging films were reviewed to evaluate the accuracy of daily treatments for 28 de novo patients with Hodgkin's disease treated with curative intent between September 1978 and September 1983. Each film was compared with the original simulation film by three independent observers. Each observer graded each film for accuracy in the superior mediastinal, axillary, and inferior mediastinal areas and for overall conformity to the treatment plan. Grades ranged from 1 to 3: grade 1 denoted accuracy within +/- 0.5 cm of the treatment plan, grade 2 denoted minor deviations greater than 0.5 cm but with no tumor or prophylactic treatment areas shielded, and grade 3 denoted an unacceptable setup. The results in 28 patients (1,186 films) showed that 84% of the films were within 0.5 cm of original plan, 15% had minor deviations, and 1% were considered unacceptable. Three patients in the study developed recurrence of Hodgkin's disease in the chest. In one of these patients, 4 of 40 films were unacceptable, but recurrence was in lung parenchyma in an area not designated for treatment. Errors in treatment setup in this small sample were not a factor in the likelihood of disease recurrence in the chest. Daily imaging films have helped decrease the number of minor deviations and unacceptable setups, compared with previous experiences.

Squamous cell carcinoma of the head and neck treated with radiation therapy: the role of neck dissection for clinically positive neck nodes.

This is an analysis of 161 patients with squamous cell carcinoma of the head and neck treated with irradiation to the primary site and neck followed by a neck dissection(s) for clinically positive neck nodes. Patients were treated between October 1964 and December 1982; there was a minimum 2-year follow-up. Fifty-two patients were deleted from analysis of neck disease control because they died of intercurrent disease or cancer less than 2 years from treatment with the neck continuously disease-free. All patients are included in the analysis of complications. Neck disease control rate was the same for radiation plus neck dissection or radiation therapy alone for solitary nodes less than 3 cm. As the size and number of nodes increased, there was a higher rate of neck disease control for combined treatment as compared with irradiation alone. The neck disease control rate, size for size, was lower for patients with fixed nodes and for those with residual tumor in the pathologic specimen. There was no difference in neck disease control as a function of the interval between irradiation and neck dissection. For nodes less than or equal to 6 cm, a minimum node dose of 5000 rad appeared to be sufficient for control, whereas for nodes greater than 6 cm, at least 6000 rad appeared to be required for optimal control. Fixed nodes required a higher dose compared to mobile masses. The incidence of postoperative complications was increased with maximum subcutaneous doses of greater than or equal to 6000 rad. There was also an increased incidence of postoperative complications for patients undergoing simultaneous, as compared with staged, bilateral neck dissection.

Stage IB or IIA-B carcinoma of the intact uterine cervix treated with irradiation: a multivariate analysis.

Although treatment results for Stage IB-IIA-B carcinoma of the cervix are generally stratified only by stage, several authors have found that other parameters such as tumor size, patient age, histology, and pretreatment hematocrit may influence pelvic control and/or survival. This is an analysis of 306 patients with carcinoma of the cervix treated with irradiation alone at the University of Florida between October 1964 and June 1984. Results were analyzed for the end points of pelvic control, distant metastasis, relapse-free survival, and overall survival. Stage for stage, there was a decrease of at least 20 percentage points in pelvic control rates of tumors greater than or equal to 6 cm versus those of tumors 0 to 3 cm in diameter, by univariate analysis; a similar pattern was also observed for the end point of relapse-free survival. When patients were stratified by Stages IB-IIA (greater than or equal to 6 cm and less than 6 cm) and IIB (greater than or equal to 6 and less than 6 cm), there was a clear pattern of improved pelvic control and relapse-free survival for patients over 50 years old and for patients with pretreatment hematocrits greater than 40%. The parameters of stage, tumor size, patient age, histology, and pretreatment hematocrit were evaluated in a multivariate analysis. For the end points of pelvic control, distant metastasis, and relapse-free survival, only tumor size was of independent prognostic significance for all three end points with p-values of 0.022, 0.003, and 0.0006, respectively. Stage did not show independent prognostic significance for any of these end points with p-values of 0.257, 0.878, and 0.284, respectively. The data suggest that tumor size is an important prognostic factor and should be incorporated into the reporting of cervical cancer treatment results.

The role of radiation therapy in inverted papilloma of the nasal cavity and paranasal sinuses.

Between December 1969 and March 1985, seven patients with advanced biologically aggressive inverted or cylindrical cell papillomas were treated with irradiation at the University of Florida. Three patients were treated with radiation therapy alone, and four patients were irradiated either before (one patient) or after (three patients) resection. No recurrences were observed in six patients at 4.5, 7, 8, 8, 9, and 20 years following treatment (including two who died of intercurrent disease at 7 and 9 years after radiation therapy without evidence of recurrent tumor). One patient treated with irradiation alone for an advanced recurrent papilloma developed a local recurrence extending into the frontal lobe of the brain and died 17 months after radiation therapy. None of the patients experienced a significant complication of irradiation. Although surgery is generally the primary treatment modality for this disease, radiation therapy should be considered for patients with advanced, incompletely resected, or unresectable lesions.

Analysis of time-dose factors in clinically positive neck nodes treated with irradiation alone in squamous cell carcinoma of the head and neck.

This is a retrospective analysis of time-dose factors in 139 patients with 238 evaluable clinically positive lymph nodes treated with external beam radiation therapy alone to the primary lesion and neck for squamous cell carcinoma of the head and neck at the University of Florida from October 1964 through April 1980. Lymph node control by lymph node size was 8/8 (100%) for less than 1.0 cm, 51/62 (82%) for 1.0 cm, 68/82 (83%) for 1.5-2.0 cm, 24/40 (60%) for 2.5-3.0 cm, 24/38 (63%) for 3.5-6.0 cm, and 0/8 (0%) for greater than or equal to 7.0 cm. Lymph node control was also influenced by dose, overall treatment time, and fractionation schedule; these factors were interrelated and appeared to increase in importance as the size of the lymph node increased.

Carcinoma of the cervical esophagus treated with radiation therapy using a four-field box technique.

This is a retrospective analysis of 16 patients with carcinoma of the cervical esophagus treated with radiation therapy at the University of Florida between September 1966 and March 1979. There is a minimum 2-year followup. Analysis of local control revealed 1/1 T1, 0/3 T2, 2/8 T3, and 1/2 TX lesions that were controlled by radiation therapy for 33, 47, 55, and 80 months. Two patients died less than 2 years after treatment without evidence of cancer. Excluding the sole T1 lesion, there were no local controls below 6700 rad; 3 of 5 lesions were controlled at doses in excess of 6700 rad. Late complications were stenosis (2 patients) and Lhermitte's syndrome (1 patient). An external beam technique consisting of an isocentric four-field box with a beeswax compensator has been devised in an effort to solve the technical problems in delivering high-dose radiation to the primary and regional nodes without producing myelitis.

Elective ilioinguinal lymph node irradiation.

Most radiologists accept that modest doses of irradiation (4500-5000 rad/4 1/2-5 weeks) can control subclinical regional lymph node metastases from squamous cell carcinomas of the head and neck and adenocarcinomas of the breast. There have been few reports concerning elective irradiation of the ilioinguinal region. Between October 1964 and March 1980, 91 patients whose primary cancers placed the ilioinguinal lymph nodes at risk received elective irradiation at the University of Florida. Included are patients with cancers of the vulva, penis, urethra, anus and lower anal canal, and cervix or vaginal cancers that involved the distal one-third of the vagina. In 81 patients, both inguinal areas were clinically negative; in 10 patients, one inguinal area was positive and the other negative by clinical examination. Tumor doses most commonly used were 4500-5000 rad/5 weeks (180 rad to 200 rad per fraction). With a minimum two-year follow-up, there were only two regional failures in patients whose primaries were controlled; both failures occurred outside of the radiation fields. The single significant complication was a bilateral femoral neck fracture. The inguinal areas of four patients developed mild to moderate fibrosis. One patient with moderate fibrosis had bilateral mild leg edema that was questionably related to irradiation. No other instances of leg or genital edema were noted. Complications were dose-related. The advantages and disadvantages of elective ilioinguinal node irradiation versus elective inguinal lymph node dissection or no elective treatment are discussed.

Results of twice-a-day irradiation of squamous cell carcinomas of the head and neck.

The results of twice-a-day irradiation for moderately advanced and advanced squamous cell carcinomas of the head and neck in 57 patients, treated at the University of Florida between March 1978 and July 1981, are reviewed. Fifty patients received irradiation alone to the primary site with or without neck dissection; 7 patients received preoperative irradiation (5040-6000 rad) followed in 4-6 weeks by resection of the primary tumor and neck dissection(s). Two 120 rad treatments were administered daily, with a 4-6 hour interval between fractions. External beam tumor doses were usually 7440-7680 rad when irradiation alone was used for the primary lesion; 2 of 3 T2 and 11 of 13 (85%) T3 lesions that received greater than or equal to 7440 rad remain locally controlled at 2-5 years' follow-up. External beam doses of 7440 rad controlled only 1 of 10 T4 cancers; higher doses controlled 3 of 8 T4 lesions. One severe complication of irradiation and 2 severe complications of salvage surgery have occurred in the group that received irradiation alone to the primary lesion. Five of the 7 patients who received planned combined preoperative irradiation plus surgery to the primary tumor were alive and free of disease at 2 years. Absolute disease-free survival at 2 years for the entire patient group was 23/57 (40%).

Patterns of recurrence in adenocarcinoma of the rectum and rectosigmoid treated with surgery alone: implications in treatment planning with adjuvant radiation therapy.

This is an analysis of 140 patients with adenocarcinoma of the rectum and rectosigmoid treated with surgery alone at the University of Florida between May 1959 and April 1976. Patients in the study group had a complete resection, as determined by the surgeon and the pathologist, and no evidence of distant metastasis at the completion of the operation. There is a 5 year minimum follow-up. Local-regional recurrence rates were noted to vary with histologic grade, length of the lesion, and pathologic stage. Approximately 60% of local-regional and distant recurrences were noted by 2 years after treatment, and 92-95% were noted by 5 years. Evaluation of patient status at 5 years revealed that 0% (Stage CIS), 0% (A), 17% (B1), 13% (B2), 17% (C1), and 28% (C2) had developed local-regional recurrence without demonstrable distant metastasis. Complications and crude 5 year survival rates are presented and current treatment modifications discussed.

Squamous cell carcinoma of the supraglottic larynx treated with radical irradiation: analysis of treatment parameters and results.

Eighty-one patients were treated with radical radiation therapy, with or without immediate neck dissection(s), for squamous cell carcinoma of the supraglottic larynx from October 1964 through May 1981. There is a 2-year minimum follow-up on all patients; 75/81 (93%) have a minimum 3-year follow-up, and 58/81 (72%) have at least a 5-year follow-up. Patients were staged according to the 1983 AJCC staging system. Patients were excluded from the local control analysis if they died less than 2 years from treatment with the primary site controlled. The initial local control rates and ultimate local control rates after surgical salvage of irradiation failures were as follows: T1, 11/12 (92%) and 12/12 (100%); T2, 20/26 (77%) and 23/26 (88%); T3, 9/14 (64%) and 11/14 (79%); and T4, 2/11 (18%) and 5/11 (45%). The incidence of severe complications was 3/81 (3.7%). The 5-year absolute and determinate survival rates by AJCC stage were as follows: I, 6/12 (50%) and 6/6 (100%); II, 5/6 (83%) and 5/5 (100%); III, 4/8 (50%) and 4/5 (80%); and IV, 6/32 (19%) and 6/26 (23%).

The impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity in early-stage Hodgkin's disease.

A retrospective analysis of patients with supradiaphragmatic Stage I-II Hodgkin's disease was performed to assess the impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity. One hundred twenty patients were treated with radiotherapy (RT) alone; 38 received total nodal (including pelvic) irradiation (TNI), 63 received modified total nodal (excluding pelvic) irradiation (MTNI), and 19 received involved-field or mantle irradiation only (less than MTNI). Thirty-three patients received combined-modality therapy. In laparotomy-staged (PS) patients treated with RT alone, the overall treatment failure rate was 13% after TNI, 24% after MTNI, and 43% after less than MTNI. The pelvic failure rate in PS patients was 0% after TNI, 9% after MTNI, and 29% after less than MTNI. Cause-specific deaths in patients treated with RT alone occurred in 10% following less than MTNI, 13% following MTNI, and 10% following TNI. Cause-specific deaths due to pelvic failure in patients treated with RT alone occurred in 5% following IF and 6% following MTNI, and also occurred in 7% of patients receiving combined-modality therapy. The potential disadvantages of elective pelvic irradiation in early-stage Hodgkin's disease include compromise of future tolerance of chemotherapy in the event of treatment failure, and infertility. Gonadal function was assessed in 67 patients less than 35 years old at the time of treatment. Compromise of gonadal function was correlated with the lack of special testicular shielding during pelvic irradiation and chemotherapy in the male, and with no oophoropexy before pelvic irradiation in the female. Twelve of 26 patients with recurrence after either less than MTNI or MTNI, with or without chemotherapy, were alive and without evidence of disease at greater than 2 years after completing salvage therapy, compared with 7 of 11 patients with recurrence after TNI.