Peter H. Blitzer

Reanalysis of the RTOG study of the palliation of symptomatic osseous metastasis

This is a reanalysis of the data from the Radiation Therapy Oncology Group (RTOG) study of the palliation of metastasis to bone. The RTOG multicenter clinical trial studied pain relief in 759 patients randomly assigned to a variety of dose‐fractionation schedules: 270 cGy × 15 fractions, 300 × 10, 300 × 5, 400 × 5, and 500 × 5. The multivariate statistical technique of logistic regression was used. The results differed from a previous report in that number of fractions was statistically significantly related to complete combined relief (that is, absence of pain and cessation of the use of narcotics). Also, the time dose factor (TDF) isoeffect conversion did not accurately predict tumor response. The conclusion is that protracted dose‐fractionation schedules are more effective than short course schedules.

Radiation therapy in the management of medically inoperable carcinoma of the lungs: Results and implications for future treatment strategies

Surgery is the treatment of choice for resectable non-small cell lung carcinoma. For patients who are medically unable to tolerate a surgical resection or who refuse surgery, radiation therapy is an acceptable alternative. We reviewed the records of 152 patients with medically inoperable non-small cell lung carcinoma treated at our institution between 1982 and 1990. Patients with metastatic disease, mediastinal lymph node involvement or unresectable tumors were excluded. The actuarial overall survival at 2 and 5 years was 40% and 10%, respectively. The disease-free survival at 2 and 5 years was 31% and 15%. The disease-free survival for patients with T1 tumors was 55% at 2 years, versus 20 and 25% for T2 and T3 lesions, respectively (p = .0006). Increasing tumor dose was also associated with increasing disease-free survival (p = .0143). Overall, 66% percent of the patients were considered to have failed. Of these, 70% showed a component of local failure and 45% failed distantly. Patients with T1 tumors experienced a lower probability of failing locally or distantly than did patients with T2 or T3 tumors. A reduced risk of local and distant failure was seen for patients treated to doses of greater than 65 Gray, especially for T1 tumors. We conclude that radical radiation therapy is an effective treatment for small tumors when treated to doses of 65 Gray or more. Since local failure is the prominent pattern of relapse in patients with large tumors, new therapeutic strategies should be considered for this patient group.

Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: Long-term follow-up of RTOG study 73-03

This is a report of a 10-year median follow-up of a randomized, prospective study investigating the optimal sequencing of radiation therapy (RT) in relation to surgery for operable advanced head and neck cancer. In May 1973, the Radiation Therapy Oncology Group (RTOG) began a Phase III study of preoperative radiation therapy (50.0 Gy) versus postoperative radiation therapy (60.0 Gy) for supraglottic larynx and hypopharynx primaries. Of 277 evaluable patients, duration of follow-up is 9-15 years, with 7.6% patients lost to follow-up before 7 years. Loco-regional control was significantly better for 141 postoperative radiation therapy patients than for 136 preoperative radiation therapy patients (p = 0.04), but absolute survival was not affected (p = 0.15). When the analysis was restricted to supraglottic larynx primaries (60 postoperative radiation therapy patients versus 58 preoperative radiation therapy patients), the difference for loco-regional control was highly significant (p = .007), but not for survival (p = 0.18). In considering only supraglottic larynx, 78% of loco-regional failures occurred in the first 2 years. Thirty-one percent (18/58) of preoperative patients failed locally within 2 years versus 18% (11/60) of postoperative patients. After 2 years, distant metastases and second primaries became the predominant failure pattern, especially in postoperative radiation therapy patients. This shift in the late failure pattern along with the increased number of unrelated deaths negated any advantage in absolute survival for postoperative radiation therapy patients. The rates of severe surgical and radiation therapy complications were similar between the two arms. Because of an increased incidence of late distant metastases and secondary primaries, additional therapeutic intervention is required beyond surgery and postoperative irradiation to impact significantly upon survival.

Twice-a-day radiation therapy for cancer of the head and neck

Experience with the twice‐a‐day (BID) radiation therapy program for carcinomas of the head and neck areas is presented. The program consists of 1.6 Gy per fraction, two fractions per day with 4 hours between fractions, for 12 days, 5 days a week. After 38.4 Gy, the patient is given a 2‐week break for symptoms of acute mucositis to subside and then twice‐a‐day radiation therapy is resumed with similar fraction size, two fractions a day for an additional 8 days to bring the total dose to 64 Gy. In some instances the primary site was boosted to an additional BID day with a maximum of 67.2 Gy. The spinal cord dose was limited to 38.4 Gy. A subset of 321 patients with squamous cell carcinoma of the oral cavity (61 patients), oropharynx (74 patients), and larynx (186 patients) treated by this program is reported. Marked improvement in local control rate at 36 months was observed for advanced tumors (T3 and T4) and with nodal disease by BID radiation therapy program as compared to conventional once‐a‐day (QD) radiation therapy program. The improvement in local control for early lesions, T1 and T2 when treated with BID radiation therapy was not noted to reach a statistically significant level. However, the successful results are quite different when compared to QD radiation therapy program, with a trend suggesting that significant difference might exist if additional patients had been entered into the studies. Acute mucosal reactions are generally more severe than those produced by QD continuous radiation therapy, but the duration of symptoms is shorter. Late effects on the normal tissues, as observed during the 4‐year follow‐up period, show no undue subcutaneous or mucosal reactions nor an increase in chondronecrosis or osteoradionecrosis. With the dose limited to 38.4 Gy in 2.5 weeks to the spinal cord, no case of radiation myelitis has been encountered.

Preoperative irradiation for unresectable rectal and rectosigmoid carcinomas

The records of 25 patients with unresectable carcinoma of the rectum and rectosigmoid who received preoperative radiation therapy (RT) were reviewed. Twenty patients were considered to be resectable following RT (80%). Sixteen patients (64%) underwent curative resections. All patients with unresectable tumors following RT died with tumor within two and one half years (median survival, 11 months). For patients undergoing curative resection, the probability of two‐ and five‐year survival was 56% and 43%, respectively. In this latter group, five of seven patients with treatment failures (71%) had a pelvic component of disease. The incidence of pelvic recurrence was correlated with the pathologic stage, extent of resection and preoperative radiation dose. The need for more aggressive treatment for patients with these advanced tumors is emphasized. Future treatment alternatives are discussed.

Complications of intraoperative radiation therapy

The ability to demonstrate an improvement in therapeutic ratio is critical in assessing new treatment modalities; an evaluation of treatment complications is essential for this purpose. We have studied the severe complications occurring after treatment with intraoperative radiation therapy (IORT) in patients with locally advanced carcinoma of the rectum. Four groups of patients were compared: Group 1 (80 patients) had treatment with surgery alone for mobile and resectable tumors; Group 2 (23 patients) had treatment with high dose preoperative irradiation followed by surgical resection for tumors which were fixed to adjacent structures and initially unresectable for cure; Group 3 (24 patients, primary disease) and Group 4 (17 patients, locally recurrent disease) had locally advanced tumors as in Group 2 but were treated with IORT after preoperative irradiation and attempted surgical resection. All but 3 complications occurred within one year of therapy. Severe complications were seen in 16% of patients in Group 1, 35% in Group 2, 21% in Group 3 and 47% in Group 4 (32% in Groups 3 and 4 combined). There was a statistically insignificant increase (p = .10) in the complication rate in all irradiated patients (locally advanced tumors) compared to surgery alone (clinically mobile tumors). These data indicate no increase in severe complications with the use of IORT. If the ongoing studies continue to show improved local control with the use of IORT, expanded use of this modality may be warranted.

Prognostic Factors in Carcinoma of the Ureter

The records and pathological slides of 60 patients with ureteral cancer were reviewed with particular attention being paid to the tumor-adjacent mucosa. Mucosal abnormalities increased as grade and stage increased but their presence did not correlate with survival nor with the presence of urothelial tumors elsewhere, that is previous, concomitant and subsequent tumors. Patients with papillary and solid tumors survived equally well. Survival among patients with stage B tumors was better than that reported previously (82 per cent survived 5 years).

Treatment of Malignant Tumors of the Spermatic Cord: A Study of 10 Cases and a Review of the Literature

Ten patients with sarcoma of the spermatic cord were treated at our hospital between 1940 and 1977. Although there are 191 reported cases in the literature controversy remains concerning optimal treatment. In our series of 10 patients 5 of 7 (71 per cent) followed for more than 5 years postoperatively have suffered local recurrence. Thus, we believe that this treatment is inadequate and recommend postoperative radiation therapy to the scrotum and pelvis. Of our patients 2 suffered recurrence in the retroperitoneal lymphatics and we favor dissection of these nodes as part of the initial treatment.

Twice-a-day radiation therapy for supraglottic carcinoma

This is a report of a group of 106 patients with supraglottic carcinomas treated by the twice-a-day radiation therapy program at the Massachusetts General Hospital from October 1979 through April 1984. The program consisted of 1.6 Gy per fraction, 2 fractions a day, 5 days a week for a total of 64 Gy with 2 weeks rest after the twelfth b.i.d. day. The local control of this group of patients was compared to that of 79 patients treated by the conventional once-a-day program with a daily fraction of 1.8 Gy for a total of 65 Gy, at the same institution during the 4 years immediately prior to the b.i.d. program. The 3 year actuarial local control rate for the entire group following the twice-a-day program was 76% as compared to 50% after the once-a-day program. The difference was significant, p = 0.001. For the T1 and T2 lesions, the corresponding rates were 88 and 63%, respectively, with a p value of 0.029. The rates for T3 and T4 lesions were 66 and 33%, respectively, p = 0.0037. The study indicated that the twice-a-day radiation therapy program as outlined is effective in treatment of supraglottic carcinoma, and is more markedly effective in advanced lesions. Late radiation effects are minimal and salvage surgery is possible for radiation therapy failures. To date, no patient developed radiation myelitis following the b.i.d. program with the dose to the spinal cord limited to 38.4 Gy in 2.5 weeks.

Current Results of Proton Beam Irradiation of Uveal Melanomas

Proton beam irradiation has been used for the treatment of 241 uveal melanomas over the past 7 1/2 years. Twelve melanomas (5%) were small, 99 (41%) medium, 103 (43%) large and 27 (1%) extra-large melanomas. The mean length of follow-up was 21 months and the median 15 months. Ninety-four percent of the treated lesions with a follow-up more than two years and 65% of tumors with shorter follow-up showed regression. The most recent visual acuity was 20/40 or better in 47% and 20/100 or better in 66%. Ten eyes were enucleated because of complications (9) or continued tumor growth (1). Thirteen patients developed metastases from 4 to 50 months of treatment. Our data indicate that proton irradiation can be used to treat melanomas of various sizes and in a variety of locations, and preliminary results suggest that proton therapy has no deleterious effect on the likelihood of the development of metastases.