Patterns of failure in squamous cell carcinoma of the vagina treated with definitive radiotherapy alone: what is the appropriate treatment volume?

The purpose of this study was to review treatment results, sites of failure, and complications in relation to the irradiation volume for carcinoma of the vagina treated with radiotherapy alone. A retrospective review of 65 patients with histologically confirmed squamous cell carcinoma of the vagina who received definitive radiotherapy was undertaken. The 5-year cause-specific survival rates were as follows: Stage I, 91%; Stage IIA (paravaginal extension), 90%; Stage IIB, 55%; Stage III, 89%; and Stage IVA, 62%. The pelvic disease control rates at 5 years were as follows: Stage I, 74%; Stage IIA, 90%; Stage IIB, 79%; Stage III, 89%; and Stage IVA, 67%. Recurrence in the pelvis occurred in 22% of patients. Eighty-five percent of pelvis recurrences were in the primary treatment field. Although pelvic control rates were not increased by use of larger treatment fields (>2,700 cm(3)), moderate acute and late effects were increased with these fields. Carcinoma of the vagina appears to have a different failure pattern than carcinoma of the cervix. The primary failure sites are the vagina and the paracolpal tissues and the inguinal nodes. Because of this, the superior edge of the pelvic fields does not have to extend above the bottom of the sacroiliac joints except with advanced lesions.

Skin cancer of the head and neck with clinical perineural invasion.

PURPOSE: To review treatment and outcomes in 62 patients with clinical and/or gross evidence of perineural invasion from skin cancer of the head and neck. METHODS AND MATERIALS: Sixty-two patients received radiotherapy at the University of Florida as part or all of their treatment between January 1965 and April 1995. All patients had clinical signs and symptoms of perineural involvement and/or documentation of tumor extending to grossly involve nerve(s). Twenty-one patients underwent therapy for previously untreated lesions, including 12 who received radiotherapy alone and nine who had surgery with postoperative radiotherapy. Forty-one patients underwent therapy for recurrent lesions, including 18 treated with radiotherapy alone and 23 who received preoperative or postoperative radiotherapy. RESULTS: Factors on multivariate analysis that predicted local control included patient age, previously untreated vs. recurrent lesions, presence of clinical symptoms, and extent of radiotherapy fields. Recurrence patterns were predominantly local; 26 of 31 patients (84%) who developed local recurrence after treatment had recurrent cancer limited to the primary site. CONCLUSIONS: Many patients with skin cancer and symptomatic perineural invasion have disease that is incompletely resectable. Approximately half these patients will be cured with aggressive irradiation alone or combined with surgery. Age, prior treatment, and clinical symptoms influence the likelihood of cure.

The optimal dose of radiation in Hodgkin's disease: an analysis of clinical and treatment factors affecting in-field disease control.

PURPOSE: The purpose of this study is to analyze the effect of radiation dose, as well as other clinical and therapeutic factors, on in-field disease control. PATIENTS AND MATERIALS: The study population comprised 232 patients with Stage I and II Hodgkin's disease (HD) treated with curative intent at the University of Florida with radiotherapy (RT) alone (169 patients) or chemotherapy and radiotherapy (CMT) (63 patients). Sites of involvement and radiation doses were prospectively recorded and correlated with sites of disease recurrence. RESULTS: Freedom from relapse and absolute survival rates at 10 years were as follows: 76% and 77%, entire group; 76% and 80%, RT group; 79% and 70%, CMT group; 85% and 78%, Stage I; and 71% and 77%, Stage II. Treatment failure occurred in 50 patients (22%) including in-field failure in 22 patients (9%). In-field failure was rare in electively treated sites. Multivariate analysis of clinical factors (tumor size, number of sites involved, B-symptoms, gender, histology, age, and site of involvement) and treatment factors (use of chemotherapy, number of cycles of chemotherapy, radiation dose, radiation treatment volume, and radiation treatment time) showed only tumor size (p = 0.0001) to be significantly correlated with in-field disease control. In RT patients, the in-field failure rate according to tumor size was as follows: 0% for < or = 3 cm; 4% for > 3 cm and < or = 6 cm; 23% for > 6 cm and < or = 9 cm; and 36% for > 9 cm. In CMT patients, the in-field failure rate was as follows: 0% for < or = 3 cm; 0% for > 3 and < or = 6 cm; 5% for > 6 cm and < or = 9 cm; and 26% for > 9 cm. In-field recurrence was not a predominant pattern of failure in RT patients with small tumors (< or = 6 cm); thus, the difference in in-field control in tumors < or = 6 cm between doses < or = 35 Gy (6%) and doses > or = 36 Gy (0%) was not statistically significant. In larger tumors (> 6 cm), in-field recurrence was a predominant pattern of failure; the in-field failure rate in RT patients with tumors > 6 cm of 30% for doses < or = 35 Gy was not significantly different from 25% for doses > 35 Gy. In moderately bulky tumors (> 6 cm and < or = 9 cm), the addition of chemotherapy did appear to increase in-field disease control; the in-field failure rate was 23% with RT and 5% with CMT (p = 0.07). CONCLUSION: Our data do not demonstrate statistically significant evidence of increasing tumor control in HD with doses > 30 Gy. The data do show that increasing tumor size is associated with increased rates of in-field failure, and the addition of chemotherapy may improve in-field disease control in tumors > 6 cm. In-field recurrence in large tumors remains a predominant pattern of failure, however, and the role of radiation doses higher than 30-35 Gy in this high-risk subset warrants further study.

Squamous cell carcinoma of the glottic larynx: a review emphasizing the University of Florida philosophy.

BACKGROUND: Squamous cell carcinoma of the glottic larynx is strongly related to cigarette smoking and excessive ethanol intake. It is the most common head and neck cancer other than skin cancer. METHODS: We reviewed pertinent literature relative to etiology, epidemiology, and treatment results, with emphasis on the treatment philosophy at the University of Florida. RESULTS: The goals of treatment are cure and retention of a functional larynx. The probability of achieving both goals is high for patients with early disease. In contrast, a significant proportion of patients with advanced disease may be cured but must have a total laryngectomy as part of the treatment. CONCLUSIONS: Treatment options are influenced by the extent of disease and patient preference. Options include transoral laser resection, open partial laryngectomy, radiation therapy, and total laryngectomy. Adjuvant chemotherapy may have a role in advanced disease.

Ependymoma: results, prognostic factors and treatment recommendations.

PURPOSE: To review the University of Florida experience in treating ependymomas, analyze prognostic factors, and provide treatment recommendations. METHODS AND MATERIALS: Forty-one patients with ependymoma and no metastases outside the central nervous system received postoperative radiotherapy with curative intent between 1966 and 1989. Ten patients had supratentorial lesions, 22 had infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery (stereotactic biopsy, subtotal resection, or gross total resection). Most patients with high-grade lesions received radiotherapy to the craniospinal axis. Low-grade intracranial lesions received more limited treatment. Spinal cord lesions were treated using either partial spine or whole spine fields. RESULTS: Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46% (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%; supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the only factor that influenced absolute survival (p = 0.0004); other factors evaluated included grade, gender, age, duration of symptoms, resection extent, primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and days under radiotherapy treatment. CONCLUSIONS: Patients with supratentorial or infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis fields are used when spinal seeding is radiographically or pathologically evident. Spinal cord tumors are treated using localized fields to the primary site if not completely resected. Failure to control disease at the primary site remains the main impediment to cure.

An analysis of factors influencing the outcome of postoperative irradiation for squamous cell carcinoma of the oral cavity.

PURPOSE: To analyze factors influencing outcome in patients who received postoperative irradiation for advanced squamous cell carcinoma of the oral cavity. METHODS AND MATERIALS: Between October 1964 and November 1993, 134 patients with 135 previously untreated primary invasive squamous cell carcinomas of the oral cavity (excluding the lip) were treated postoperatively with continuous courses of external-beam irradiation at the University of Florida. All patients had a minimum follow-up of 2 years (analysis, December 1995). No patient was lost to follow-up. RESULTS: The 10-year actuarial rates of primary site, neck, and local-regional control were 79%, 88%, and 71%, respectively. Recurrence of cancer above the clavicles developed in 35 patients. Ninety-four percent of the recurrences were within the primary field of irradiation (anterior to the plane of the spinal cord); there were 24 recurrences at the primary site and nine in the upper neck alone. There were no failures in the neck area behind the plane of the spinal cord (i.e., the "posterior strip"). Two failures occurred in the low neck below the level of the thyroid notch. In univariate analyses, factors that affected local-regional control included pathologic stage (I-II vs. III-IV, p = 0.04), margin status (invasive cancer at the margin vs. other, p = 0.0007), multifocal tumor (p = 0.05), perineural invasion (p = 0.04), and number of indications for postoperative irradiation (p = 0.05). Extracapsular nodal extension was marginally significant (p = 0.07). In multivariate analysis, positive margins and number of indications remained significant. These factors were used to define relatively favorable (< 4 indications, margins not positive) and unfavorable (> or = 4 indications and/or margins positive for invasive cancer) groups. For both favorable and unfavorable groups, there were nonsignificant trends toward improved local-regional control for patients who began irradiation within 45-50 days, compared with those whose irradiation began later. There were also nonsignificant trends toward improved control for patients treated with shorter overall irradiation treatment courses. An analysis was also performed on the effects of duration of the overall "treatment package" (from the date of surgery until the last day of irradiation). For patients with unfavorable tumors, there was a significantly higher probability of local-regional control for patients whose overall "treatment package" was < or = 100 days (60% vs. 14%, p = 0.04). The 5-year rate of distant metastasis as the sole site of failure was 8% and was predicted by pathologic N stage (N0-N1, 3%; N2-N3, 16%, p = 0.02), as well as the presence (20%) or absence (6%) of extracapsular nodal extension (p = 0.06). The 5-year freedom-from-relapse rate was 63%. The 5-year survival and cause-specific survival rates were 50% and 67%, respectively. Four severe radiation injuries occurred (3%). CONCLUSION: This paper provides data that define relatively favorable and unfavorable groups of patients in the postoperative setting. Patients with four or more indications for irradiation and/or invasive cancer at the surgical margins have a worse outcome than patients who do not have these negative factors; this is true in spite of the fact that the unfavorable group received higher doses of radiation. Attention should be focused on not only the interval between surgery and irradiation, but also time-dose parameters and the overall duration of the treatment "package."

Postoperative radiation of open head and neck wounds--updated.

BACKGROUND: Postoperative radiotherapy is commonly used in treating head and neck cancer. A concern is the possibility of an unhealed surgical wound delaying or disrupting the treatment schedule. Our institution previously reported our experience on the outcome of radiotherapy on unhealed wounds from 1977 to 1984. METHODS: In an effort to update and enlarge this series, we reviewed the charts of patients receiving postoperative radiotherapy from 1985 to 1990. Of 267 patients, 20 had unhealed wounds or fistulas at the beginning of treatment. The wounds healed spontaneously in 17 of these patients, 1 required surgical closure, and 2 never healed. Combining our current and previous series, 452 patients had onset of postoperative radiation therapy at our institution from 1977 through 1990, of whom 33 had unhealed wounds at the onset of irradiation. RESULTS: In 22 of 33 (67%) patients, the wounds healed spontaneously (mean: 98 days, range: 36 to 304 days). Five additional patients achieved successful wound healing following surgical closure (mean: 281 days, range; 112 to 608 days). The remaining 6 patients died before healing was complete (4 patients) or were lost to follow-up (2 patients) at 16 and 27 months before wound healing occurred. Nine patients in this study are alive with no evidence of disease, 19 died of cancer, and 5 died of other causes. CONCLUSIONS: When there are indications to deliver irradiation in the postoperative setting, it is desirable to initiate treatment within 6 weeks of the data of surgery. Although it is preferable to have completely closed operative wounds prior to irradiation, some consideration must be given to initiating irradiation in the face of incompletely closed wounds when it is anticipated that healing time will be prolonged. In some patients, the wounds continue to heal during the course of irradiation, or will stabilize, and can be surgically managed after irradiation is completed or may spontaneously heal after treatment. Excessive delays in initiating appropriate cancer therapy may lead to recurrence prior to irradiation; such recurrences are rarely successfully salvaged.

Response of the normal eye to high dose radiotherapy.

Radiation therapy of tumors near the eye or optic nerves often requires incidental irradiation of these structures, even when they are not clinically involved by tumor. Depending on the radiation treatment volume and dose required, radiation injury to the lens, lacrimal apparatus, retina, or optic nerve may result. The time to expression and severity of injury are dose-dependent. This paper reviews the results of 157 patients who were followed for a minimum of 3 years after radiotherapy for primary extracranial tumors at the University of Florida, in which the lacrimal gland, lens, retina, and/or optic nerve(s) received irradiation. This review shows that, after treatment at approximately 1.8 to 2.0 Gy per fraction, the incidence of severe dry-eye syndrome, retinopathy, and optic neuropathy appears to increase steeply after doses of 40, 50, and 60 Gy, respectively.

Management of minor salivary gland carcinomas.

PURPOSE: To assess the role of radiotherapy alone or in combination with surgery in the treatment of patients with malignant minor salivary gland carcinomas. METHODS AND MATERIALS: Between October 1964 and November 1992, 95 patients with minor salivary gland carcinomas of the head and neck received radiotherapy with curative intent. Eighty-seven patients were previously untreated, and 8 were treated for postsurgical recurrence. Fifty-one patients were treated with radiotherapy alone, and 44 were treated by surgical resection plus radiotherapy. Patients were staged according to the 1983 American Joint Committee on Cancer (AJCC) staging criteria for squamous cell carcinomas. RESULTS: The 20-year actuarial rate of local control was 57% with no significant difference according to histologic type. When tumor stage was taken into consideration, there were no significant differences in local control according to tumor site. The 12-year actuarial probability of distant metastases was 40% (19% as the only site of failure). In multivariate analyses, local control was significantly affected only by tumor stage and treatment type (combined therapy better than radiotherapy alone); tumor stage was a significant predictor of cause-specific survival and freedom from relapse. Freedom-from-relapse rates were higher for patients who received combined treatment (p = 0.068). CONCLUSIONS: Treatment of minor salivary gland carcinomas is usually by combined surgery and radiotherapy, but there are situations where surgery alone or radiotherapy alone may be used. The ability to control these tumors with radiotherapy alone is not widely recognized. In the present series, the tumor was locally controlled in 20 patients with previously untreated primary lesions after radiotherapy alone (2.5 to 21 years) and in 4 other patients who were treated by radiotherapy alone for postsurgical recurrent tumor (3.5 to 14 years after radiotherapy). Contrary to the widely held belief that local recurrence after radiotherapy eventually develops in all patients with adenoid cystic carcinoma, local control has been maintained in 13 patients after radiotherapy alone; 5 of the 13 patients have been observed for 10 to 17 years.

Salvage surgery after radiotherapy failure in T1-T2 squamous cell carcinoma of the glottic larynx.

BACKGROUND: This study was undertaken to analyze the clinical course of patients who developed local (primary) recurrence after high-dose irradiation of T1 -T2 squamous cell carcinoma of the glottic larynx. METHODS: Between May 1977 and December 1989, 247 patients with previously untreated T1 and T2 invasive squamous cell carcinoma of the glottic larynx were treated for curative intent with radiotherapy. Local recurrence occurred in 26 of 247 patients (11%). Successful surgical salvage was defined as no evidence of recurrent cancer for at least 2 years after salvage surgery and continuously thereafter. RESULTS: Two patients refused to undergo salvage surgery and one patient had unresectable disease. Of 23 patients who underwent salvage surgery, 19 had a total laryngectomy and 4 had a voice-sparing procedure. One patient who was continuously free of disease, died less than 24 months after salvage surgery; this patient was excluded from all local control and survival analyses, leaving 22 patients available for analysis. Successful salvage was achieved initially in 13 (59%) of the 22 patients. Two patients with local failure after voice-sparing salvage surgery underwent completion laryngectomy; one was salvaged, so that 14 of 22 (64%) were ultimately salvaged. The rate of successful salvage did not correlate with preirradiation T stage, time to failure after irradiation, or time from clinical suspicion of recurrence to histologic proof. In a subgroup of patients (those with positive margins, tumor extension into the soft tissues of the neck, or two or more adverse histologic features), the risk of local-regional recurrence after salvage laryngectomy was 80%. CONCLUSION: There are few data in the literature regarding the clinical outcome of patients whose tumors are not controlled by initial radiotherapy. This series and previous publications from other institutions indicate that most patients who develop primary failure undergo salvage surgery, which is successful in approximately 50-80% of the patients. The rate of surgical complications is acceptable and is related to radiotherapy dose. At our institution, most patients who had recurrence after radiotherapy underwent total laryngectomy. More than 50% of the patients who experienced recurrence after irradiation originally had tumors of such extent that they would have required total laryngectomy if surgery had been recommended instead of radiotherapy for the initial treatment. It is reasonable to consider reirradiation in patients with a very high risk of local-regional recurrence after salvage laryngectomy.

Radiotherapy for early vocal cord cancer: a dosimetric analysis of 60CO versus 6 MV photons.

BACKGROUND: Currently, many patients with early vocal cord cancers are treated with 6 MV photons, but almost all the published radiotherapy data are based on patients treated with 60Co, 2-MV, or 4-MV X-rays. A theoretical risk of underdosage exists with higher energy beams due to lack of dose build-up. This dosimetric study compares 6-MV photons with 60Co. METHODS: A tissue-equivalent phantom was constructed of a stack of 0.5-cm-thick acrylic plates. With a male subject in treatment position as the model, the external surfaces of the phantom were machined to match the contour of the neck. To precisely represent the internal contour of the airway, computed tomography (CT) was performed on the subject in treatment position, with images at 0.5-cm intervals, and the airway shown on the CT was cut out of each corresponding acrylic plate. Thermoluminescent dosimetry (TLD) rods were inserted into the phantom. For each measurement, a calculated tumor dose of 10 Gy was delivered to the volume specified as the entire right true vocal cord in the phantom, with either 60Co or 6-MV photons (15 measurements were made with each). In a second series of eight experiments with each modality, TLD minichips were used to measure the dose received by the immediate surface of the vocal cords with delivery of a calculated tumor dose of 0.5 Gy. RESULTS: The doses received at the vocal cords, as well as a point 6 mm beneath the anterior skin surface, did not differ significantly for the two energies compared. The dose delivered to the skin and a point 3 mm beneath the anterior skin surface was significantly lower with the use of 6-MV photons. CONCLUSION: Although there is no difference in the dose received by the vocal cords, underdosage of the anterior tissues may occur with the use of 6-MV photons.

Oropharyngeal carcinoma treated with radiotherapy: a 30-year experience.

PURPOSE: This study was done to determine the outcome in patients with oropharyngeal carcinoma treated at the University of Florida with radiotherapy alone to the primary site, for comparison with reported results of other types of treatment. METHODS AND MATERIALS: Of a consecutive cohort of 785 patients with biopsy-proven, previously untreated, invasive squamous cell carcinoma of the oropharynx, this report is based on the 490 patients who had continuous-course irradiation with curative intent at the University of Florida between October 1964 and January 1991. All patients had a minimum 2-year follow-up. Forty-eight percent had Stage T3 or T4 disease, and 64% had clinically apparent neck node metastases. The median radiation dose was 68 Gy for once-a-day treatment and 76.8 Gy for twice-a-day treatment. Patients with advanced neck node disease had planned neck dissection(s) after radiotherapy. RESULTS: The overall local control rate after radiotherapy alone was 73%. The ultimate local control rate (including surgical salvage) was 78%. At 5 years, the probability of control of neck disease was 85%; control above the clavicles, 67%; absolute survival, 44%; cause-specific survival, 77%; distant metastasis (as the first or only site of failure), 11%. Thirteen patients (2.6%) experienced severe treatment complications. CONCLUSION: Radiotherapy results in tumor control and survival rates comparable with rates achieved with combined irradiation and surgery, with less morbidity.

Radiation therapy for sinus malignancies.

Primary tumors arising in the nasal cavity and paranasal sinuses usually are considered together. Except in the nasal cavity, where occasional lesions present early because of nasal obstruction, most lesions are advanced at presentation, and the exact site of origin may be uncertain. Radiation therapy may be used alone or in combination with surgery in the management of patients with squamous cell carcinoma of these sites.

Testicular seminoma: a failure analysis and literature review.

PURPOSE: A retrospective analysis of 74 patients with pure seminoma, treated at the University of Florida between 1964 and 1989, was undertaken. METHODS AND MATERIALS: All patients received megavoltage irradiation, with chemotherapy reserved for salvage. At 10 years, the probability of relapse-free survival was 91% for Stage I, 93% for Stage IIA, 83% for Stage IIB, and 75% for Stage III patients. RESULTS: There were seven recurrences, none of which occurred in irradiated areas. Only two of seven patients (29%) with recurrence were salvaged. CONCLUSION: A literature review revealed an increasing rate of mediastinal or supraclavicular recurrence, correlating with the size of the subdiaphragmatic disease, in Stage II patients who did not receive elective mediastinal irradiation. Recommendations are made regarding the role of elective mediastinal irradiation for Stage II disease. We conclude that patients with Stage I or II seminoma can have high cure rates when treated with radiotherapy alone. Patients with Stage III seminoma should be treated initially with cisplatin-based chemotherapy.

Salvage surgery following radiation failure in squamous cell carcinoma of the supraglottic larynx.

PURPOSE: We analyzed the clinical course of patients who developed local (primary) recurrence following high-dose irradiation of squamous cell carcinoma of the supraglottic larynx. METHODS AND MATERIALS: Between October 1964 and July 1991, 206 patients with previously untreated squamous cell carcinoma of the supraglottic larynx underwent radiotherapy with curative intent. Local failure occurred in 46 (22%) patients. Successful surgical salvage was defined as no evidence of recurrent cancer for at least 2 years after salvage surgery and continuously thereafter. RESULTS: Sixteen patients did not undergo salvage surgery because of refusal (7 patients), severe medical illness (2 patients), concurrent distant metastasis (5 patients), or unresectable neck disease (2 patients). Twenty-six patients underwent total laryngectomy, and 4 patients had a voice-sparing procedure. Successful salvage was achieved in 50% of patients who underwent surgery. The rate of successful salvage did not correlate with preirradiation T-stage or time to failure after irradiation. Most of the failures after surgery were because of failure to control the primary cancer. The overall rate of postsurgical complications was 37%. No operative or perioperative deaths occurred. The 5-year survival rate for all 46 patients, calculated from the date of irradiation failure, was 20%, while the 5-year survival rate after salvage surgery for the 30 patients who underwent the procedure was 29%. CONCLUSION: There are few data in the literature regarding the clinical outcome in patients whose tumors are not controlled by initial radiotherapy. In the current and previous series, one-half to two-thirds of patients who developed primary failure underwent salvage surgery, which was successful in approximately half of the operated patients, leading to a 25-30% rate of long-term disease-free survival among the entire group of patients who developed failure.

Advances in radiotherapy for head and neck cancer.

Selected advances in radiotherapy for treatment of head and neck cancer are reviewed. These include the role of postoperative radiotherapy, planned postirradiation neck dissection, altered fractionation, neoadjuvant chemotherapy and radiotherapy for laryngeal preservation, three-dimensional conformal treatment planning, charged particle irradiation for skull base tumors, and stereotactic radiosurgery.

Retropharyngeal adenopathy as a predictor of outcome in squamous cell carcinoma of the head and neck.

BACKGROUND: Little information about the incidence of retropharyngeal adenopathy and its impact on prognosis has been published. METHODS: For 774 patients with squamous cell carcinoma of the nasopharynx, oropharynx, hypopharynx, or supraglottic larynx, pretreatment CT and, in selected cases, MRI scans were reviewed to determine the presence of retropharyngeal adenopathy. Results were analyzed in 619 patients treated with curative intent to determine the prognostic impact of retropharyngeal adenopathy. RESULTS: The highest incidence of retropharyngeal adenopathy was seen in patients with nasopharyngeal (74%) and pharyngeal wall (19%) cancers. The number of cervical nodal groups involved was the most significant factor (p < .0001) relating to the incidence of retropharyngeal adenopathy. The rates of neck relapse (40% at 5 years) and distant metastasis were significantly higher in patients with retropharyngeal adenopathy, and the rates of 5-year relapse-free survival and absolute survival were significantly lower. CONCLUSIONS: Retropharyngeal adenopathy is a strong predictor of poor prognosis, particularly for patients with advanced neck disease.