Multimodality treatment in the management of esophageal cancer: neoadjuvant chemoradiotherapy followed by transhiatal esophagectomy.

Esophageal cancer, although not one of the more common malignancies in the United States, remains a significant problem. Nearly as many patients as are diagnosed die in the same year, regardless of the treatment employed. Surgery is considered the mainstay of therapy. Esophagectomy with the use of the stomach as a substitute is preferred. Radical procedures have not proven more effective in extending survival. Because of the poor five-year survival rate, multimodality therapy with preoperative chemoradiotherapy (neoadjuvant therapy) followed by esophagectomy has shown encouraging results. Two illustrative cases are presented, one with adenocarcinoma and one with a squamous cell carcinoma, that were treated in this manner.

Once-a-week vs conventional daily radiation treatment for lung cancer: final report.

This is the final report of a prospective randomized clinical trial which began in 1982 and explored once-a-week hypofractionation in lung cancer patients with unresectable, non-metastatic, measurable, loco-regionally advanced disease. Stratification to this protocol has been done by histology, stage, and performance status categories. Patients with ipsilateral supraclavicular and/or brain metastases as the only evidence of distant spread, have been included in the study, but were stratified and analyzed separately. The two protocol arms were: (I) Conventional daily radiation [5 x W]-5 daily fractions of 2 Gy each to a total dose of 60 Gy in 6 weeks, protecting the spinal (SC) at 45 Gy and (II) Once-a-week radiation [1 x W]-one weekly fraction of 5 Gy each to a total tumor dose of 60 Gy in 12 weeks protecting the SC at 30 Gy. A total of 150 patients have been entered. Of these, 30 pts. are inevaluable, but the reasons of non-compliance, progression of disease or death due to intercurrent disease were of equal incidence in both groups. Of the 120 evaluable patients, 63 were treated 5 x W and 57 with 1 x W therapy. Complete tumor responses are similar in both arms with 1 x W pts demonstrating a numerical advantage (26% vs 17%). The average follow-up of the entire series is 3 yrs with a range of 12-66 months. Survival data is comparable in both groups with the 12 and 24 month actuarial survival of 49% and 23% for the 5 x W arm and 59% and 29% for the 1 x W arm. 1 x W patients continue to show a better tolerance than 5 x W pts. There are sufficient long-term survivors in both arms to assess chronic toxicity. The number of patients alive at 12, 18, and 24 months were 25, 11, and 5 for the 5 x W arm and 29, 16, and 7 for the 1 x W arm. No significant differences in late reactions have been noted. The longest surviving patient in the 1 x W arm is now 48 months after treatment.

A prospective randomized trial comparing once-a-week vs daily radiation therapy for locally-advanced, non-metastatic, lung cancer: a preliminary report.

This is the first report of an on-going Phase III protocol for patients with locally-advanced, non-metastatic, measurable lung cancer. The study randomizes two arms: 6000 rad using 500 rad fractions once a week (1 X W) for 12 weeks with spinal cord (SC) protection at 3000 rad; and 6000 rad using 200 rad fractions daily (5 X W) for 6 weeks with SC protection at 4500 rad. Both arms use an initially large loco-regional field that is further reduced when tumor doses reach 3000 rad in (1 X W) arm and 5000 rad in (5 X W) arm. The protocol was activated April 1982; as of August 1984, it had accrued 100 patients of whom 68 were evaluable [29 (1 X W) and 39 (5 X W)]. There have been no major differences in tumor responses or failure patterns between the (1 X W) and (5 X W) arms; response rates have been 69 and 64%; CR 31 and 20%; total incidence of local failures 20 and 23%; and overall incidence of distant failures 34 and 43%, respectively. The (1 X W) arm has been far better tolerated with 76% of its patients free of any esophagitis and 97% without weight loss, as compared to only 33 and 67% in the (5 X W), respectively. The (1 X W) arm has not conveyed loss in tumor control effectiveness, in-treatment progression, or higher incidence of distant spread. Subacute and chronic complications have been minimal with either treatment. No fatal or life-threatening toxicities have occurred; the incidence of severe complications has been 7% in the (1 X W) arm and 8% in the (5 X W) arm. Nevertheless, the number of patients alive and at risk greater than or equal to 12 months is still relatively small; definitive statements regarding very late toxic reactions cannot yet be made. Compared to their protocyptes [a (1 X W) Pilot Study and the 6000 rad/6 weeks arm of RTOG Protocol 73-01], results in the present protocol arms have not been different from what was expected. Once a week RT yields results that appear no different from those achieved with conventional RT in lung cancer.

Cancer of uterine cervix stage IB. Treatment results and prognostic factors.

From 1969 through 1977, 210 patients with Stage IB carcinoma of the uterine cervix were treated at University of Maryland Hospital. Fifty-six patients were treated by radical hysterectomy (S), 136 patients were treated by a full course of radiation therapy (RT) only and 18 patients received radiation treatment following radical surgery (S + RT). The 5-year determinate survival rates were almost the same in the S group and RT alone group (79% and 77%, respectively). The 5-year determinate survival rate in the S + RT group was 50%, which was statistical significantly lower than S alone or RT alone groups (P less than 0.05). Several prognostic factors were analyzed in the radiated patients: the size of the primary lesion, location of the lesion within the cervix, tumor grade, age of the patients at the time of diagnosis, and complete blood count nadir during the course of radiation treatment. The only factor found to influence the prognosis was the size of the primary tumor. The patients with smaller tumors had a better prognosis; the absolute and determinate 5-year survival rates were 80% and 82%, while the absolute and determinate survival rates in the large, fungating tumor replacing the entire cervix were 56% and 60%, respectively (P less than 0.001). The complication rate was 22% in the RT alone, 22% in the S + RT, and 25% in the S alone groups.

Palliative half-body irradiation. Single and fractionated doses.

Systemic half-body irradiation (HBI) has been used extensively for the palliation of cancer pain. It has also been tried as an adjuvant therapy in patients with advanced locoregional tumors with a high propensity to disseminate and as consolidation therapy after primary systemic treatment. The limitations and toxicity of this technique have been studied extensively. Single doses of 600 rad to the upper half-body (UHB) and 800 rad to the lower half-body (LBH) have been found to achieve excellent palliative responses with an acceptable rate of complications. In order to determine the feasibility of increasing the dose of radiation delivered, a pilot study was conducted at the University of Maryland. Forty-four patients received palliative HBI. Of these, the first 36 patients received single doses to the UHB, mid-body (MB), or LHB using doses of 600 rad to the UHB and 800 rad to MB and LHB. The last consecutive eight patients received two fractions of 400 rad each, given 2-3 weeks apart. The pain response achieved by each group is similar; single dose achieved 84% complete and partial responses vs. the fractionated group, which achieved 87% complete and partial responses. The main difference between the two groups was the time necessary to achieve a response. The single dose group achieved improvement of their symptoms in 24-48 hours in approximately 70% of the patients who responded. The fractionated group achieved symptomatic response after the second dose of irradiation was given. The toxicity of both groups was similar. The acute radiation syndrome after half-body irradiation was controlled with a premedication program. Hematological toxicity was similar in both groups, and no cases of fatal radiation pneumonitis were seen. At the present time, it seems feasible to proceed with other fractionation schemes in order to try to increase the total dose delivered.

Prognosticators in recurrent breast cancer. A 15-year experience with irradiation.

After initial surgery, 133 breast cancer patients, who did not receive postoperative radiation or chemotherapy, were subsequently irradiated for recurrences in the Department of Radiation Oncology, University of Maryland Hospital. All patients have been followed for a minimum of 5 years after the treatment of recurrences. An extensive analysis was done in search of prognosticators for outcome in recurrent breast cancer. Traditional prognostic factors, such as the initial axillary status, primary surgical procedure, initial menopausal status, time and site of recurrences, distant metastases and radiation dose and field issues, were investigated. No correlation was found between the initial axillary status and the overall prognosis after recurrence. The main prognosticators were: the size of the initial breast tumor, the radiation treatment for recurrences, and the presence of, or time to, distant metastases. Initial T1-T2 breast tumors were associated with a delayed onset of recurrences and a lower incidence of chest wall relapses; in turn, both the latter situations yielded the best outcome. Radiation doses of more than 4000 rad in 4 weeks delivered with locoregional fields achieved a local control rate of 72%, and the best 5-year post-recurrence survival (57%). In 52% of the recurrent breast cancer patients, distant metastases were discovered; 70% of them occurred within 2 years from recurrence. The overall post-recurrence 5-year survival for the entire series was 40%. Both the results achieved with radiation therapy and the need for a logical strategy to approach the problem of breast cancer recurrences are discussed. The situation for a large proportion of these patients is not hopeless, and many are salvagable . Combined modality approaches could offer the best possibilities of survival. However, the importance of radiation therapy in the management of these patients cannot be denied or ignored.

Once weekly total and subtotal skin electron beam therapy for Kaposi's sarcoma.

Although Kaposi's sarcoma (KS) usually appears with solitary skin lesions, in a large percentage of these patients the disease progresses eventually to involve large extensive segments of the skin. In the past, the most frequently used approach is the irradiation of isolated lesions as they arose, hence the so-called "chasing technique." Since 1971, a technique of once weekly total skin electron beam therapy (TSEB) has been employed at Memorial Hospital for mycosis fungoides and other cutaneous malignancies involving large areas of the body. Four hundred rads once weekly for six to eight consecutive weeks are delivered to the entire skin surface by employing a 3.5 MeV electron beam. Twenty patients with KS treated by this technique have been followed for 12--98 months, median 48 months. Overall response is 100%; 17/20 (85%) obtained complete remission lasting 10--92 months, (median 48 months).

Subtotal-skin electron-beam therapy once a week for inflammatory breast carcinoma.

Subtotal-skin electron-beam therapy (SSEB) was employed once a week in the treatment of 22 patients with recurrent inflammatory breast carcinoma between 1971 and 1976. The entire upper torso received 400 rad once a week for 6 consecutive weeks, using 3.5-MeV electrons from a 6-MeV linear accelerator. Seventeen patients (77%) obtained complete response and 3 (14%) had partial response, for a total response rate of 91%. Remission lasted for six months or longer in 35% of those exhibiting complete response. Treatments were tolerated well. The authors suggest that this is an excellent palliative method of treating this rapidly progressive disease.

Complications of total nodal irradiation of Hodgkin's disease stages III and IV.

One hundred twenty-seven patients with Hodgkin's disease, Stages III-IV, received total nodal irradiation. Of these, 101 patients were managed primarily by radiation therapy employing the split course sequential segmental radiation technique called the "3 & 2". A dose of 3800-4000 rad is delivered in 2 phases in an overall period of 12 to 13 weeks (TDF 61-64; 1094-1148 rets). For various reasons, the remaining 26 patients received their mantle irradiation to full doses 3800-4000 rad in 4 weeks (TDF 63-66; 1112-1184 rets) without rest periods and a few were irradiated after failing chemotherapy. Of the 101 patients treated between 1969-1974 using the "3 & 2" technique, 2 developed pericarditis (2.0%), none manifested symptomatic pneumonitis (0%), and 3 hypothyroidism )3.0%). The low incidence of severe complications is primarily the result of the technique employed to give total nodal irradiation. The overall incidence of Herpes Zoster was 42% (53/127), and there was a slightly higher incidence when TNI was given following splenectomy.

Hepatic radiation tolerance in Hodgkin's disease patients.

Prophylactic hepatic irradiation was give to 28 "bad risk" Stage III Hodgkin's disease patients. The whole liver was given 2,000 rad in 10 days in addition to 1,800-2,000 rad to that portion included in the total nodal irradiation field. Twenty-three patients have been followed a minimum of 10 months with serial liver function tests. A transient elevation of serum enzymes has been noted at 3-12 months following hepatic irradiation in 78% (18 of 23 patients). No cases of clinical radiation hepatitis have been found in patients at risk 10 to 39 months (median, 23 months). Hepatic irradiation at this dose level appears to be tolerated without prohibitive complications.