Re-treatment of nasopharyngeal carcinoma in 53 patients.

Fifty-three patients with locally recurrent or persistent nasopharyngeal carcinoma were re-treated with megavoltage radiation therapy at The University of Texas M. D. Anderson Cancer Center from 1954 through 1989. The time from initial treatment to re-treatment ranged from 2 to 189 months (median 33 months). Documented local disease was confined to the nasopharynx in 27 patients (Group 1), while in the other 26 patients there was local spread beyond the nasopharynx (Group 2). At the time of re-treatment, nodal disease was present in 27 of the 53 cases. Forty-two patients were re-treated with external beam therapy alone and 11 with a component of brachytherapy. Re-treatment doses specified at the nasopharyngeal vault ranged from 27.5 to 99 Gy (median 57 Gy), and total cumulative dose ranged from 80 to 160 Gy (median 112 Gy). Overall 5-year actuarial local control (LC), disease-free survival (DFS), and survival rates were 35%, 18%, and 21%, respectively. Patients with Group 1 disease did better than those with Group 2 disease in terms of 5-year survival, 32% versus 9% (p = 0.01) and 5-year DFS, 23% versus 12% (p = 0.002). Nodal status at the time of re-treatment did not predict for LC or survival. The 5-year survival of patients with lymphoepitheliomas was 28% compared with 13% for patients with squamous cell carcinomas (p = 0.04). Eight patients developed severe complications from re-treatment, of which five involving the brain (two), spinal cord (one), and lower cranial nerves (two) were fatal. The incidence of severe complications was related to the total cumulative dose of external beam irradiation: 4% for patients receiving doses less than or equal to 100 Gy compared with 39% for those patients who received doses greater than 100 Gy (p = 0.066). Beginning in 1977, a combination of external beam therapy (20 to 30 Gy) and intracavitary cesium (40 to 50 Gy surface dose) was used in selected cases: 9 of the 53 patients were re-treated with this combination. Of these, 7 achieved LC with a follow-up of 7 to 102 months and none sustained a severe complication. Five-year actuarial LC, DFS, and survival in this group were 67%, 44% and 60% respectively.

Maxillary sinus carcinomas: natural history and results of postoperative radiotherapy.

Between 1969 and 1985, 73 patients with maxillary sinus cancers underwent surgical excision and postoperative radiotherapy. The clinical stage distribution by the AJC system was 3T1, 16T2, 32T3, and 22T4. Six patients had palpable lymphadenopathy at diagnosis. Surgery for the primary tumor consisted of partial or radical maxillectomy, and if disease stage indicated it, ipsilateral orbital exenteration. This was followed by radiation treatment delivered through a wedge-pair or three-field technique. All but three patients received 50-60 Gy in 2 Gy fractions to an isodose line defining the target volume. Elective neck irradiation was not routinely given. Clinically involved nodes were treated with definitive radiotherapy (five patients) or combined treatment (one patient). Forty-five patients had no evidence of disease at the last follow-up. The 5-year relapse-free survival for the whole group was 51% The overall local control rate was 78%. Patients with larger tumors, particularly if they also had histological signs of nerve invasion, had a higher recurrence rate than others. The overall nodal recurrence rate without elective neck treatment was 38% for squamous and undifferentiated carcinoma, and only 5% for adenoid cystic carcinomas. Therefore, our current recommendation is to deliver elective nodal irradiation routinely to patients with squamous or undifferentiated carcinoma, except for those who have T1 lesions. Treatment complications were vision impairment, brain and bone necrosis, trismus, hearing loss, and pituitary insufficiency. The incidence of major side effects was determined by disease extent and treatment technique. Many technical refinements were introduced in order to limit the dose to normal tissues in an attempt to reduce the complication rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Concomitant boost radiotherapy schedules in the treatment of carcinoma of the oropharynx and nasopharynx.

Concomitant boost schedules are characterized by delivering the boost (10-12 fractions) as second daily treatments during rather than following the basic wide field irradiations. This results in shortening the overall time to administer 69-72 Gy from 7 1/2-8 weeks to 6 weeks, which we hoped would improve the tumor control rate by reducing the opportunity for tumor clonogens to regenerate during treatment. From August 1985 to August 1988, 79 patients with T2-4 carcinomas of the oropharynx (72 patients) or nasopharynx (7 patients) were treated according to 1 of the 3 variants of the concomitant boost technique. The median age of patients was 60 years (range: 19-84 years) and the male-to-female ratio was 2.6. The overall 2-year actuarial primary and nodal control rates by radiotherapy alone were 74% and 76%, respectively. The ultimate 2-year control rates after surgical salvage were 82% and 84%, respectively. If the boost given during the last 2-2 1/2 weeks of basic treatment, a slightly better primary control rate (p = 0.11) resulted than if the boost was delivered during the first 2-2 1/2 weeks or twice a week throughout the basic treatment. The 2-year actuarial primary control rate of the 13 patients receiving induction chemotherapy prior to radiotherapy was significantly lower than that of patients treated with radiation only (81% vs 34%, p = 0.01), but this could be partly attributed to a more advanced stage in the chemotherapy group. The acute mucosal reactions were, as expected, more severe than those observed with conventional fractionation. Fifty patients developed confluent mucositis covering more than half of the boost area. Such reactions lasted for more than 6 weeks in seven patients. Late complications, however, so far observed, have been few. Three patients experienced chronic mucosal tenderness, 1 chronic mucosal ulceration, 2 transient bone exposure, and 1 carotid rupture following salvage surgery. The results so far appear to be better than the outcome of conventional radiotherapy. Its real value will be determined in a prospective randomized study.

The essential role of radiation therapy in securing locoregional control of Merkel cell carcinoma.

Between 1966 and 1987, 54 patients with non-disseminated Merkel cell carcinoma (MCC) were treated with curative intent at the University of Texas M. D. Anderson Cancer Center. The primary tumor site was in the head and neck in 38 patients. The majority of the patients (57%) were referred with locoregionally recurrent disease. For the whole group, survival was 30% after 5 years. Patients who presented with nodal involvement had a median survival of 13 months compared with 40 months for node-negative patients (p less than .04). Only 4/37 patients treated initially by surgery alone were locoregionally controlled, with a median time to recurrence of 4.9 months. Salvage with radiation therapy was attempted in 18 patients (after additional surgery in 14), but was successful in only four. The predominant failure pattern in this subgroup was distant metastases, occurring as a component of initial recurrence in 12/18 patients. Prior to 1982, the philosophy of initial therapy was to give postoperative irradiation only to patients with large primaries or nodal involvement. Subsequently, postoperative radiotherapy has been recommended routinely, and all five patients treated with this approach remain disease-free. In total, 31 patients (including 10 patients with gross disease) were irradiated at M. D. Anderson; only one developed an in-field locoregional recurrence as an initial site of failure. However, three marginal recurrences occurred. The median dose to the primary tumor, first echelon nodes, and supraclavicular nodes was 60, 51, and 50 Gy, respectively. Our current recommendation for initial treatment is excision of the primary tumor followed by irradiation with generous fields to include the primary tumor site and draining regional lymphatics to doses of 46-50 Gy in 2 Gy fractions. For gross unresected disease, 56-60 Gy is recommended. The role of adjuvant systemic therapy remains to be defined.

Supraglottic laryngectomy for intermediate-stage cancer: U.T. M.D. Anderson Cancer Center experience with combined therapy.

We reviewed the records of all patients with previously untreated squamous cell carcinomas of the supraglottic larynx who presented to The University of Texas M.D. Anderson Cancer Center from 1974 to 1987. Of 404 patients, 60 (15%) underwent supraglottic laryngectomy and functional anterior neck dissection as a primary modality of therapy; these patients were studied. Fifty of the 60 patients (83%) received adjunctive postoperative radiotherapy. Tumor-free survival was 96% at 2 years and 91% at 5 years. There were no local failures, 4 regional failures, and 3 distant metastases. Second cancers, mostly of the lung, occurred in 9 patients (15%). Three patients required completion laryngectomies for intractable aspiration. Analysis of deglutition and tracheal decannulation rehabilitation revealed a higher incidence of complications in patients who underwent arytenoidectomies.

Primary radiotherapy in the treatment of stage I and II oral tongue cancers: importance of the proportion of therapy delivered with interstitial therapy.

From January 1963 through December 1979, 103 patients with Stage T1N0 and T2N0 squamous cell carcinomas of the oral tongue were treated with definitive radiotherapy. The primary was Stage T1 in 18 patients and T2 in 85 patients. Therapy to the primary consisted of interstitial therapy only in 18 patients, 16-37 Gy in 2.4-4.0 Gy fractions followed by interstitial therapy to doses of 38-55 Gy in 31 patients, external therapy of 40-50 Gy with interstitial therapy of 20-40 Gy in 46 patients, and external beam only to doses of 45-82 Gy in 8 patients. Follow-up ranged from 2 to 290 months (median 159 months). Five of the 8 patients treated with external therapy alone and 6 of the 18 patients treated with interstitial therapy failed at the primary site. In those patients treated with a combination of external and interstitial therapy the 2-year local control rate was 92% for patients treated with external therapy to doses of less than 40 Gy combined with a moderately high dose of brachytherapy, compared with 65% for patients who received external therapy to doses of greater than or equal to 40 Gy with lower brachytherapy doses (p = .01). Conversely the risk of failure in the neck was directly related to the dose delivered by external beam therapy. In field recurrence occurred in 44% of patients receiving no therapy to the neck. 27% in those receiving less than 40 Gy, and 11% in those patients with neck treatment to greater than or equal to 40 Gy. Eleven of 87 (13%) of patients who were at risk for complications for greater than or equal to 24 months developed severe complications; severe complications were more likely to occur in the group who received most of their therapy with external beam irradiation. These data show that a high dose of interstitial therapy is necessary to secure optimum local control of early primary tongue cancer. Because of the high frequency of moderate to severe late complications in this series we have adopted a policy of initial surgery for most oral tongue cancers with postoperative radiotherapy if indicated by pathological features predictive of a high rate of local-regional failure.

Regional radiotherapy as adjuvant treatment for head and neck malignant melanoma. Preliminary results.

From 1983 through 1988, 83 patients with high-risk cutaneous malignant melanoma (primary lesion thicker than 1.5 mm or palpable lymphadenopathy) of the head and neck region were enrolled in a study designed to assess the efficacy of a few large doses of radiation (24 to 30 Gy in 4 to 5 fractions). The actuarial 2-year locoregional control rates for the three groups were 95%, 90%, and 83%, respectively. Corresponding survival rates were 80%, 71%, and 69%. The majority of failures were due to distant metastases. Locoregional control rates were better than those reported earlier with surgery alone for comparable patients. The treatment morbidity was minimal.

Response of plateau-phase C3H 10T1/2 cells to radiation and concurrent administration of bleomycin.

The mode and extent of interaction between bleomycin and radiation were assessed in contact-inhibited cultures of C3H 10T1/2 cells, which in confluent monolayers display a low turnover rate and behave more like late-responding normal tissues in vivo with respect to response to fractionated radiotherapy (i.e., having a low alpha/beta value). Plateau-phase C3H 10T1/2 cultures were exposed to gamma rays delivered in 1, 2, 5, or 10 fractions. The radiation doses administered ranged from 2 Gy in one exposure to 26 Gy in 10 fractions. Half of the cultures were also treated with 1 micrograms/ml of bleomycin for 5 days during which radiation was also given. It was found that 1 micrograms/ml of bleomycin sterilized approximately 40% of the C3H 10T1/2 cells in the cultures. The radiation dose-survival curves of various fractionation schedules (1, 2, 5, and 10 fractions) plus bleomycin were displaced downward (i.e., to lower survival levels) but not modified in shape. The alpha/beta ratios, parameters of the linear-quadratic model of cell survival, were 2.6 (2.2-3.1) and 2.4 (1.8-3.1) Gy for radiation only and radiation plus bleomycin, respectively. This observation indicates that the effect of combining irradiation and bleomycin on C3H 10T1/2 cells in monolayers was additive.

Hyperfractionated radiotherapy in the treatment of squamous cell carcinomas of the supraglottic larynx.

From January 1984 through December 1987, 41 patients with squamous cell carcinomas of the supraglottic larynx were treated with hyperfractionated radiotherapy at The University of Texas M. D. Anderson Cancer Center. Two patients had T1 primary tumors, 23 had T2, 15 had T3, and 1 had T4; 29 patients had no clinical evidence of nodal disease in the neck, 4 had N1, 5 had N2, and 3 had N3. Radiotherapy was delivered in 120 cGy fractions twice per day, with at least 4 hr between treatments. Total doses ranged from 7200 to 7900 cGy (median, 7680 cGy). Three patients had planned neck dissections before or after radiotherapy, and three patients with fixed vocal cord lesions were treated with preradiation chemotherapy. At the time of analysis, median follow-up was 22 months. Four patients have had failures at the primary tumor site. There has been one recurrence in the neck in a patient who also had a recurrence at the primary site. Three of the four patients with recurrences have been successfully treated with salvage surgery. Exclusive of surgical salvage, the actuarial disease-free local control rates above the clavicles in the 38 patients with T2 and T3 cancers were 96% at 1 year and 87% at 2 years. In comparison, the rates were 82% and 76% for a group of 98 patients with T2 and T3 lesions treated at this institution from 1970 to 1981 with 6500-7000 cGy given in 200 cGy fraction per day. As predicted, acute reactions were more severe but late complications were not increased in patients who received hyperfractionated radiotherapy compared with those treated by conventionally fractionated therapy. Only two patients have developed severe late complications one of whom required laryngectomy. Hyperfractionated radiotherapy appears to provide improved local control with a similar incidence of late complications when compared with conventionally fractionated therapy. To further improve the therapeutic ratio, our current protocol has been amended by reducing the large field dose per fraction to 110 cGy (with a 2 day protraction of overall time) and requiring a minimum interfraction interval of 6 hr.