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BACKGROUND. Two-thirds of patients with squamous cell carcinomas of the head and neck (SCCHN) at diagnosis have advanced disease with projected 5-year survival rates of 30%. In those patients with distant metastatic or previously treated recurrent disease, response rate to the standard regimen of cisplatin and 5-fluorouracil is approximately 30%. The authors investigated the use of paclitaxel and carboplatin in a limited Phase II study in recurrent or metastatic SCCHN to evaluate tumor response, time to progression, survival, and toxicities of this regimen. METHODS. Patients with recurrent or metastatic SCCHN not amenable to further surgical or radiation therapy were treated with 200 mg/m 2 by 3-hour infusion of paclitaxel followed by carboplatin at an area under the concentration time curve of 6 mg/mL/minute via a 20 ‐30-minute infusion every 3 weeks. RESULTS. Thirty-seven patients were enrolled. Ninety-five percent of patients had received prior surgery and postoperative radiotherapy. The overall response rate was 27% (95% confidence interval, 13‐ 41%) with 1 complete and 9 PRs. Median survival of all patients was 4.9 months, and 1-year survival rate was 16%. There was a 43% response rate and 15.7-month median survival rate in patients with only distant metastatic disease and 38% response rate and a 4.5-month median survival in patients with locoregional and metastatic disease. The response rate for patients with only locoregional recurrence was 7% with a median survival of 4.8 months. Grade 3‐ 4 myelotoxicity occurred in 24% of cycles administered. There were two treatment-related deaths due to neutropenic fever and one additional death on study may have been caused by treatment-induced thrombocytopenia. CONCLUSIONS. The combination of paclitaxel and carboplatin is significantly myelotoxic and ineffective in patients with previously treated locoregionally recurrent SCCHN, whereas it deserves further evaluation in those patients with distant metastatic disease alone. In those patients with locoregional disease, other more innovative treatments are needed. Cancer 2001;92:2334 ‐ 40. © 2001 American Cancer Society.

ore than 11,000 cases of laryngeal carcinoma present annually M in the U.S.,’ and 95% of these tumors have a squamous cell histology.’ The majority of T1 and T2 classified tumors of the glottis are treated solely with radiation therapy, with the remainder treated ~urgically.~*~ Depending on the series, the 3-year disease free survival rate after primary radiation therapy ranges from 70-90% for Stages 1-11 and 30-50% for Stages III-IV.5 Despite refinements in therapy, there has been no significant improvement in the 5-year survival rates of patients with glottic carcinoma over the last 3 decades.’ Accurate identification of patients whose tumors are likely to be refractory to radiation therapy is needed to direct them to other, more appropriate

BACKGROUND. The Radiation Therapy Oncology Group conducts large-scale prospective, randomized trials to test new concepts in cancer patient care and provide information about pretreatment and treatment factors that may influence outcome. METHODS. Recursive partitioning analysis (RPA) was used to examine the data derived from 2105 patients. RPA grouped patients according to the influence of tumor, of host, and of treatment variables on outcome. RESULTS. For survival, the most important factor was T classification. For lesions less than T3, the primary tumor was the next most important factor, whereas for T3 and T4 lesions the Karnofsky score was the next most predictive factor. Six distinct groups were formed by RPA, with median survivals ranging from 6.8 to 151.8 months. For local-regional control, the N classification was the most important factor. For patients with no adenopathy, T classification was the next most important factor, whereas for patients with adenopathy, the number of treatment fractions was the next most important factor. Such analysis created 5 distinct groups. In the most favorable, the median time to local-regional relapse has not yet been reached. In the least favorable group, fewer than 50% of the patients experienced complete response at any time following treatment. CONCLUSIONS. RPA clarifies the relative importance and potential interactions of pretreatment and treatment variables and should permit more accurate stratification of patients in future trials.

Background. Clinical trials of hyperfractionated radiation therapy and induction chemotherapy followed by standard radiation therapy have shown improved survival in patients with unresectable nonsmall cell lung cancer (NSCLC). Radiosensitization may improve local tumor control when chemotherapy is given concurrently with hyperfractionated radiation therapy, but also may increase toxicity. A Phase I/II trial, Radiation Therapy Oncology Group 90-15, was designed to evaluate whether this strategy could improve survival with acceptable toxicity and be part of a Phase III trial of chemoradiation sequencing. Methods. Vinblastine (5 mg/M 2 weekly X 5 weeks) and cisplatin (75 mg/M 2 days 1, 29, and 50) were given during twice-daily irradiation (1.2 Gy, 6 hours apart) to 69.6 Gy in 58 fractions in 6 weeks. Eligible patients had American Joint Committee on Cancer (AJCC) Stage II (unresected) or IIIA-B NSCLC and Karnofsky performance status 70 or greater ; there were no weight loss restrictions. Results. Of 42 eligible patients, 76% had greater than 5% weight loss, 45% had T4 primary tumors, and 62% were Stage IIIB. All protocol treatment was completed in 53%. Acute toxicity was predominantly hematologic with 19 of 42 (45%) having Grade 4 toxicity or higher, three (7%) with septic death. Ten of 42 (24%) had Grade 3 or higher esophagitis. There were two (4.7%) patients with Grade 3 or higher (1 lung and 1 esophagus) and two (4.7%) with Grade 4 or higher (1 lung and 1 hematologic) late toxicities. Median survival time was 12.2 months, with an overall 1-year survival of 54%, an estimated 2 year survival of 28% and a 1-year progression free survival of 38%. Conclusions. For patients with unresectable nonsmall cell lung cancer, who were not selected on the basis of weight loss, concurrent hyperfractionated irradiation and chemotherapy had more intense acute toxicity than hyperfractionation alone, but late toxicity was acceptable. One and 2-year survival rates were 54 and 28%, respectively. Cancer 1995 ; 75 :2337-44.

BACKGROUND Information regarding results of treatment and possible prognostic factors in patients with maxillary sinus carcinoma is limited. METHODS Between 1969-1995, 48 consecutive patients presented to the study department for curative treatment of maxillary sinus carcinoma. Tumor classification according to the American Joint Committee on Cancer staging system was T1 in 1 patient, T2 in 6 patients, T3 in 17 patients, and T4 in 24 patients. The N classification was NO in 43 patients, N2a in 1 patient, N2b in 3 patients, and N2c in 1 patient. Treatment to the primary site was comprised of surgery (Sx) and radiation therapy (RT) in 37 patients and RT alone in 11 patients. RESULTS There was a difference in disease free survival between patients who underwent Sx + RT compared with patients who received RT alone; combined therapy results were more favorable. The most common pattern of recurrence was in the primary site, which was found in 22 of 48 patients (45.8%). For patients who underwent Sx + RT, local control at 3 and 5 years was 65.2% and 59.2%, respectively; for patients who received RT alone, local control at both 3 and 5 years was 22.7%. There were 12 late complications found in 8 patients: fistula formation (5 patients), trismus (3 patients), osteonecrosis (1 patient), retinopathy (1 patient), cellulitis (1 patient), and nasal stenosis (1 patient). CONCLUSIONS The type of treatment to the primary site is an important determinant of disease free survival and local control. Failure at the primary site is the main problem in the curative treatment of patients with maxillary sinus carcinoma; efforts to improve survival in these patients should be directed toward improvement of local control. Cancer 1998;83:457-465. © 1998 American Cancer Society.

The optimal sequence for clinical utilization of combined radiotherapy and hyperthermia is not known. The clinical trials have resulted in similar responses whether hyperthermia is given before or after radiation. Moreover, studies addressing the best sequence for an entire course of multifractionated hyperthermia and radiation are lacking. In these experiments, the importance of sequencing of heat and irradiation in a multifractionated treatment regimen in RIF-1 murine tumors was studied. It was observed that a close sequence of heat and irradiation is more beneficial than separate cytotoxic action. When heat and irradiation were given simultaneously, (within 1 hour) 67% to 75% of the tumors were cured. Heat and irradiation given sequentially (the entire course of one following the entire course of the other, each separated by 72 hours) cured 20% of the tumors. No tumors were cured when treated with heat or irradiation alone. The tumor regrowth time (mean tumor doubling time) is much longer in simultaneous treatment than in sequential treatment. It appears that heating first decreases the effectiveness of subsequent irradiation, causing a shorter growth delay than the opposite sequence. Heat alone does not alter the tumor bed permanently, but irradiation seems to do so, resulting in a slower rate of growth upon recurrence.

One hundred patients with inoperable (80) or unresectable (20) bronchogenic carcinoma without evidence of spread beyond the thorax and supraclavicular nodes were planned for radical radiotherapy. Seventy-six patients received continuous irradiation (6000 rads in 30 treatments in 6 weeks, TDF 99) and 24 received split course therapy (2 courses of 2500 rads in 10 treatments with a 3 week break between courses, TDF 88). Forty-three patients had squamous cell carcinoma or adenocarcinoma and were considered to have favorable prognostic factors, while 57 patients had unfavorable prognostic factors: undifferentiated large cell or small cell carcinoma, supraclavicular metastases, SVC obstruction, superior sulcus tumors, or bone erosion in continuity with the tumor. Ninety-two patients completed the planned course of treatment. In patients completing treatment, local control of cancer within the irradiated volume was achieved in 58.5% of continuously irradiated patients and 45.4% of patients receiving split course therapy. Median survival was 1.2 months in patients not completing treatment and 12 months for the patients who completed treatment; 19% of the total group survived 3 years. Median and 3 year survivals of 14 months and 20.4% and of 9 months and 11% were observed for patients treated continuously and by the split course techniques, respectively. Corresponding survival figures for patients with favorable and unfavorable prognostic signs were 21 months and 26%, and 4 months and 11%, respectively. Implications of these data for treatment planning and patient selection for radical radiotherapy in bronchogenic carcinoma are discussed.

Sixty-five visceral metastases from malignant melanoma were treated with radiation therapy. A variety of total doses and dose fractions were used. Significant palliation was achieved in 40 of 65 (62%) symptomatic lesions. There was no correlation between total dose or dose fraction size and significant palliation. Brain and bone metastases were separately analyzed. Nineteen of 28 (68%) bone metastases were palliated. Appendicular bony metastases were more likely to be palliated than axial bony metastases (88% versus 60%). The palliation of bone metastases did not depend on total dose given or fraction size. Nine of 23 (39%) symptomatic brain metastases were palliated. There was no difference in the rate of palliation between solitary and multiple brain metastases. Palliation of brain lesions was not dependent on fraction size, although there was a trend to better palliation with higher total doses. These findings suggest that unlike treating cutaneous or nodal melanoma lesions for local control, there is no advantage in large fraction size when treating with palliative intent visceral melanoma lesions.

This report updates a previous publication describing the experience at the Mallinckrodt Institute of Radiology with irradiation and hyperthermia in the treatment of superficial metastatic and recurrent malignant tumors. In a dose-seeking Phase I-II clinical study, a total of 101 lesions have been treated. Twenty-two tumors were treated with doses of irradiation ranging from 1000 to 3000 rad and the rest with doses between 3000 and 4000 rad. Irradiation was delivered twice weekly (every 72 hours) in tumor doses of 400 rad, usually with electrons (9–16 MeV). Hyperthermia was initiated within 30 minutes following irradiation, most of the patients being treated with 915 MHz microwaves, 41–43°C, for 60–90 minutes every 72 hours. Adequate temperatures were reached in most lesions measuring less than 2 cm in thickness, 70% of those 2–4 cm and only in 30% of those thicker than 4 cm. Of 36 measurable lesions in the head and neck, 20 had a complete response and 12 a partial response. In 16 of the 20 patients (80%) showing a complete response the tumor was controlled from three to 36 months. Of 30 adenocarcinoma of the breast lesions, recurrent in the chest wall, 16 showed a complete response and 9 a partial regression. Twelve of the 16 lesions that regressed completely (71.4%) showed long-lasting tumor control. Of 22 metastatic or recurrent melanoma lesions, 16 had a complete regression and six a partial response. Of the 16 patients with complete response, 13 (81%) had no evidence of recurrence lasting from three to 36 months. Three sarcoma lesions responded well to the combination of irradiation and heat and did not recur after treatment. Patients treated with doses larger than 3000 rad in the head and neck or in the chest wall (epidermoid carcinoma or adenocarcinoma, respectively) showed better tumor response than those treated with lower doses. However, in melanoma satisfactory results (80% or higher response) were observed with doses as low as 2000 rad. This combined therapy has been well tolerated by the normal tissues. In 6% of the patients there was evidence of tumor necrosis with ulceration and in 5% thermal burns which healed after 2 to 3 months, with conservative management. Subcutaneous fibrosis and some skin atrophy developed in about one third of the patients, probably due to the additional doses of irradiation delivered after previous definitive radiotherapy. These preliminary observations suggest enhanced tumor response and control after moderate doses of irradiation and hyperthermia. Efforts must be intensified to develop adequate equipment to satisfactorily produce heat and to measure temperatures in clinical settings, thus paving the way for appropriately designed clinical trials to test the efficacy of hyperthermia in patients with deep seated lesions and advanced primary tumors.