Don R. Goffinet

Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial.

Between 1978 and 1984, the Northern California Oncology Group (NCOG) conducted a randomized trial to study the efficacy of combined radiotherapy (RT) and chemotherapy (CT) for stage III or IV inoperable head and neck cancer. One hundred four patients were randomized to receive: (1) RT alone, or (2) RT plus CT. RT consisted of 7,000 cGy to the involved areas and 5,000 cGy to uninvolved neck at 180 cGy/fraction, five fractions/wk. CT consisted of bleomycin, 5 U intravenously (IV), twice weekly during RT, followed by bleomycin, 15 U IV, and methotrexate, 25 mg/m2 IV weekly for 16 weeks after completion of RT. Fifty-one patients in the RT alone group and 45 in the combined treatment group were evaluable. The local-regional complete response (CR) rate was 45% v 67% (P = .056); the 2-year local-regional control rate, including salvage surgery, was 26% v 64% (P = .001); and the incidence of distant metastasis was 24% v 38% (P greater than .25), for the RT alone and RT plus CT groups, respectively. The relapse-free survival curves were significantly different (P = .041), favoring the combined treatment. However, the survival curves were not significantly different (P = .16). Patient compliance to maintenance CT was poor. Bleomycin significantly increased the acute radiation mucositis, although the difference in late normal tissue toxicity was not statistically significant. Thus, bleomycin and concurrent RT produced a more favorable CR rate, local-regional control rate, and relapse-free survival, but the difference in survival was not statistically significant.

Carcinoma of the nasopharynx. Eighteen years' experience with megavoltage radiation therapy†

From 1956 through 1973, 82 patients with carcinoma of the nasopharynx received high dose megavoltage radiation therapy at Stanford University. The actuarial disease‐free (NED) survival was 62% at 5 years and 56% at 10 years. The NED survivals at 5 years for patients with T1, T2, and T3 lesions were 76%, 68%, and 55%, respectively. No T4 patients were salvaged, but two of 10 patients who presented with cranial nerve dysfunction were long‐term survivors. The degree of nodal involvement also had prognostic significance. Involved lymph nodes were successfully controlled in all instances when doses of at least 6500 rads were given. Initial treatment failed in 32 patients. In 24 (75%) this occurred within 18 months. Thirteen patients with initial recurrences in head and neck sites were retreated and three remain alive. Survival after retreatment ranged from 2 months to 10 years, with a median of 16 months. Although nearly one‐third (6/17) of the patients with local recurrences had initial T1 or T2 lesions, there have been no failures in patients treated for these early stages in the last 7 years. This may be attributed to the use of larger treatment fields. Likewise, prophylactic irradiation of the neck was always successful in preventing nodal disease if the primary site was controlled.

Chemotherapy as a Substitute for Surgery in the Treatment of Advanced Resectable Head and Neck Cancer A Report From the Northern California Oncology Group

This trial determines the feasibility for patients with resectable Stages III/IV head and neck cancer who achieved a complete response to induction chemotherapy of eliminating surgery from their treatment program. Thirty patients were treated with three cycles of cisplatin and 5‐fluorouracil (5‐FU), followed by reendoscopy and biopsy. Twelve patients achieved a complete pathologic response at the primary and received radiation (interstitial and/or external beam) only. The remainder underwent surgical resection and postoperative radiation. At 2 years, the relapse‐free survival was 52%, and the survival was 53% for the entire group. For the 12 complete responders who had surgery eliminated, the relapse‐free survival was 60%, and the survival was 70%. This pilot study suggests that for patients with resectable disease who achieve a complete pathologic response to induction chemotherapy at their primary, it is feasible to omit surgery and treat with primary radiation without compromise in survival. This approach warrants further study in a randomized trial.

Radiation-induced carotid artery disease

Nine patients with atherosclerotic carotid artery disease associated with neck radiation were compared to 40 control patients. The data suggest that significant differences in age, incidence of coronary and peripheral vascular disease, elevated lipids and serum cholesterol, and the angiographic incidence of disseminated atherosclerosis justify the description of radiation‐induced carotid disease as a clinical entity. Elevated serum cholesterol and hyperlipidemia may contribute to the development of radiation‐induced vascular disease. Successful surgical reconstruction does not appear to be influenced by the prior radiotherapy, although periarterial fibrosis and increased difficulty in separating the plaques from the vascular media was encountered.

Herpes Zoster-Varicella Infections and Lymphoma

Abstract In 1 130 patients with lymphoma seen at the Stanford Medical Center between 1959 and 1969, there were 129 cases of herpes zoster-varicella infections, an incidence of 11.4%, including 21 d...

Bladder cancer: results of radiation therapy in 384 patients

Between 1957 and 1972, 384 patients with bladder cancers were treated initially with megavoltage radiation therapy. Actuarial five-year survival ranged from 35 to 42% for Stages A and B1 tumors, and was 35, 22 and 7%, respectively, for Stages B2, C and D carcinomas. Approximately 30-40% of deeply invasive tumors confined to the bladder can be controlled with radiation therapy alone, directed solely to the bladder itself.

IMPROVED LOCAL CONTROL WITH STEREOTACTIC RADIOSURGICAL BOOST IN PATIENTS WITH NASOPHARYNGEAL CARCINOMA

PURPOSE Treatment of nasopharyngeal carcinoma using conventional external beam radiotherapy (EBRT) alone is associated with a significant risk of local recurrence. Stereotactic radiosurgery (STR) was used to boost the tumor site after EBRT to improve local control. METHODS AND MATERIALS Forty-five nasopharyngeal carcinoma patients received a STR boost after EBRT at Stanford University. Seven had T1, 16 had T2, 4 had T3, and 18 had T4 tumors (1997 American Joint Commission on Cancer staging). Ten had Stage II, 8 had Stage III, and 27 had Stage IV neoplasms. Most patients received 66 Gy of EBRT delivered at 2 Gy/fraction. Thirty-six received concurrent cisplatin-based chemotherapy. STR was delivered to the primary site 4-6 weeks after EBRT in one fraction of 7-15 Gy. RESULTS At a medium follow-up of 31 months, no local failures had occurred. The 3-year local control rate was 100%, the freedom from distant metastasis rate was 69%, the progression-free survival rate was 71%, and the overall survival rate was 75%. Univariate and multivariate analyses revealed N stage (favoring N0-N1, p = 0.02, hazard ratio HR 4.2) and World Health Organization histologic type (favoring type III, p = 0.002, HR 13) as significant factors for freedom from distant metastasis. World Health Organization histologic type (p = 0.004, HR 10.5) and age (p = 0.01, HR 1.07/y) were significant factors for survival. Late toxicity included transient cranial nerve weakness in 4, radiation-related retinopathy in 1, and asymptomatic temporal lobe necrosis in 3 patients who originally had intracranial tumor extension. CONCLUSION STR boost after EBRT provided excellent local control in nasopharyngeal carcinoma patients. The incidence of late toxicity was acceptable. More effective systemic treatment is needed to achieve improved survival.

Management of Breast Cancer After Hodgkin’s Disease

PURPOSE To evaluate the incidence, detection, pathology, management, and prognosis of breast cancer occurring after Hodgkins disease. PATIENTS AND METHODS Seventy-one cases of breast cancer in 65 survivors of Hodgkins disease were analyzed. RESULTS The median age at diagnosis was 24.6 years for Hodgkins disease and 42.6 years for breast cancer. The relative risk for invasive breast cancer after Hodgkins disease was 4.7 (95% confidence interval, 3.4 to 6. 0) compared with an age-matched cohort. Cancers were detected by self-examination (63%), mammography (30%), and physician exam (7%). The histologic distribution paralleled that reported in the general population (85% ductal histology) as did other features (27% positive axillary lymph nodes, 63% positive estrogen receptors, and 25% family history). Although 87% of tumors were less than 4 cm, 95% were managed with mastectomy because of prior radiation. Two women underwent lumpectomy with breast irradiation. One of these patients developed tissue necrosis in the region of overlap with the prior mantle field. The incidence of bilateral breast cancer was 10%. Adjuvant systemic therapy was well tolerated; doxorubicin was used infrequently. Ten-year disease-specific survival was as follows: in-situ disease, 100%; stage I, 88%; stage II, 55%; stage III, 60%; and stage IV, zero. CONCLUSION The risk of breast cancer is increased after Hodgkins disease. Screening has been successful in detecting early-stage cancers. Pathologic features and prognosis are similar to that reported in the general population. Repeat irradiation of the breast can lead to tissue necrosis, and thus, mastectomy remains the standard of care in most cases.

Radiosurgery for skull base malignancies and nasopharyngeal carcinoma

PURPOSE Patients with skull base lesions present a challenging management problem because of intractable symptoms and limited therapeutic options. In 1989 we began treating selected patients with skull base lesions using linac stereotactic radiosurgery. In this study the efficacy and toxicity of this therapeutic modality is investigated. METHODS AND MATERIALS Forty-seven patients with 59 malignant skull base lesions were treated with linac radiosurgery between 1989 and 1995. Eleven patients were treated for primary nasopharyngeal carcinoma using radiosurgery as a boost (7 Gy-16 Gy, median: 12 Gy) to the nasopharynx after a course of fractionated radiotherapy (64.8-70 Gy) without chemotherapy. Another 37 patients were treated for 48 skull base metastases or local recurrences from primary head and neck cancers. Eight of these patients had 12 locally recurrent nasopharyngeal carcinoma lesions occuring 6-96 months after standard radiotherapy, including one patient with nasopharyngeal carcinoma who developed a regional relapse after radiotherapy with a stereotactic boost. Lesion volumes by CT or MRI ranged from 0 to 51 cc (median: 8 cc). Radiation doses of 7.0 Gy-35.0 Gy (median: 20.0 Gy) were delivered to recurrent lesions, usually as a single fraction. RESULTS All 11 patients who received radiosurgery as a nasopharyngeal boost after standard fractionated radiotherapy remain locally controlled (follow-up: 2-34 months, median: 18). However, one patient required a second radiosurgical treatment for regional relapse outside the initial radiosurgery volume. Thirty-three of 48 (69%) recurrent/metastatic lesions have been locally controlled, including 7 of 12 locally recurrent nasopharyngeal lesions. Follow-up for all patients with recurrent lesions ranged from 1 to 60 months (median: 9 months). Local control did not correlate with lesion size (p = 0.80), histology (p = 0.78), or radiosurgical dose (p = 0.44). Major complications developed after 5 of 59 treatments (8.4%), including three cranial nerve palsies, one CSF leak, and one trismus. Complications were not correlated with radiosurgical volume (p = 0.20), prior skull base irradiation (p = 0.90), or radiosurgery dose > 20 Gy (p = 0.49). CONCLUSION Stereotactic radiosurgery is a reasonable treatment modality for patients with skull base malignancies, including patients with primary and recurrent nasopharyngeal carcinoma. The dose distribution obtained with stereotactic radiosurgery provides better homogeneity than an intracavitary implant when used as a boost for nasopharyngeal lesions, especially lesions which involve areas distant to the nasopharyngeal mucosa.

24-Hour infusion of cis-platinum in head and neck cancers

Eighteen patients with advanced squamous cell cancer of the head and neck were treated with cis‐diamminedichloroplatinum in a 24‐hour infusion. The most frequent dose used was 80 mg/m2 repeated every three weeks. Six were treated preoperatively for Stage III or IV disease, and twelve were treated for recurrent disease. The overall response rate was 72% with one complete remission, >50% regression in six patients, and 25‐50% regression in six patients. Toxicity was minimal: creatinine >2 in 6% of courses, leukopenia in 9%, anemia in 29%, vomiting in 76%, and documented minimal hearing loss in one patient. Plasma and urine platinum levels during infusion are presented. The dosage of 80 mg/m2 administered over 24 hours gives a response rate in head and neck cancers equivalent to that reported with higher doses given by rapid infusion, and toxicity is minimal. Cancer 42:2135–2140, 1978.