Robert G. Slawson

Pancoast's Tumor: Irradiation or Surgery?

Seventy-three patients with Pancoasts tumor treated at the University of Maryland Hospital between 1955 and 1978 were reviewed. Three were 34 squamous cell carcinomas, 13 undifferentiated, 10 adenocarcinomas, 4 mixed adenosquamous, 1 alveolar cell, and 11 undetermined. Twenty-nine patients received irradiation, with 7% survival at 3 years; 19 patients underwent preoperative irradiation followed by en bloc resection of chest wall, with 23% survival at 3 years; 5 patients underwent extended resection, with 60% survival at 3 years; and 18 patients underwent operation followed by irradiation, with 7% survival at 3 years. Retrospective staging of 42 patients undergoing operation indicated that 22 (52%) were inoperable. Prognosis was related to staging of the disease, the extent of local invasion, nodal involvement, cell type, and adequacy of operation.

Primary mediastinal seminoma

Three new cases of primary mediastinal seminoma are presented, and 124 other cases in the literature are reviewed. These tumors primarily affect white males in the third decade. Chest pain is the most common symptom, but 20 per cent of the patients can be asymptomatic. Testicular atrophy occurred in only 7 patients. In one of these a testicular seminoma developed seven years after treatment of a primary mediastinal tumor. Supraclavicular adenopathies were found in 10 patients. Chest x-ray films typically show an anterior mediastinal noncalcified mass with smooth lobulated borders. Twenty-eight of 74 surgical resections attempted were successful; 13 of these received adjuvant irradiation. Of 64 cases in which radiation therapy was the primary mode of treatment, local failures occurred only in 7 cases. These tumors spread primarily by distant metastases. Theories of tumoral origin and patterns of spread are discussed. A dose of 3,000 rad in three weeks and 4,500 rad in four and one-half weeks to the mediastinum and supraclavicular areas is recommended for minimal and bulky disease. Primary mediastinal seminoma is as radiosensitive as its testicular counterpart.

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.

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.

The role of post-operative radiation in the prevention of heterotopic ossification in patients with post-traumatic acetabular fracture

Heterotopic ossification (HO) with subsequent pain and limitation of motion of the lower extremity is a common and significant problem for patients who suffer traumatic acetabular fracture (TAF). The incidence of heterotopic ossification is markedly increased for patients requiring surgical repair depending on the degree of trauma and the type of surgical repair necessary. Radiation therapy (RT) has proven to be the most effective surgical adjunct for the prevention of heterotopic ossification in patients undergoing total hip replacement (THR), but has not been reported in patients with traumatic fracture and repair. This report details an experience with patients treated at a Shock Trauma Center with extensile repair and immediate (within 48 hr) post-operative radiation therapy given as 5 daily fractions of 2 Gy in 5 to 7 days to a total dose of 10 Gy using megavoltage radiation therapy. A total of 30 consecutive patients (RT group) have been treated at our institution since June 1985. The last 20 patients treated with surgery only (non-RT group) prior to initiation of this study were used as a control group. Heterotopic ossification was seen to some degree in 50% of all radiation therapy patients, but was severe in only three of 30 (10%) of cases [three (10%) had Brooker III HO and no patients had ankylosis (Brooker IV HO)]. In contrast, some degree of heterotopic ossification was seen in 90% of the non-radiation therapy patients, and was severe in 10 of 20 (50%) of patients [seven (35%) had Brooker III HO whereas three (15%) had ankylosis (Brooker IV)]. This difference is significant for both total incidence and incidence of severe cases (p less than 0.01). This reduction in heterotopic ossification incidence approaches the magnitude reported for high-risk patients with total hip replacement. Even though the incidence of severe heterotopic ossification after radiation therapy for total hip replacement is approximately 5% and for traumatic acetabular fracture patients it is double (10%), the actual incidence of heterotopic ossification without radiation therapy is different in the two conditions. For total hip replacement, the incidence is about 30% and for traumatic acetabular fracture it is 50%. Radiation therapy has again proven itself to be an excellent surgical adjunct to prevent heterotopic ossification, this time in traumatic acetabular fracture patients.

Long-term outcome of Gamma Knife stereotactic radiosurgery for arteriovenous malformations graded by the Spetzler-Martin classification

OBJECT The object of this study was to assess outcomes in patients with arteriovenous malformations (AVMs) treated by Gamma Knife stereotactic radiosurgery (SRS); lesions were stratified by size, symptomatology, and Spetzler-Martin (S-M) grade. METHODS The authors performed a retrospective analysis of 102 patients treated for an AVM with single-dose or staged-dose SRS between 1993 and 2004. Lesions were grouped by S-M grade, as hemorrhagic or nonhemorrhagic, and as small (< 3 cm) or large (≥ 3 cm). Outcomes included death, morbidity (new neurological deficit, new-onset seizure, or hemorrhage/rehemorrhage), nidus obliteration, and Karnofsky Performance Scale score. RESULTS The mean follow-up was 8.5 years (range 5-16 years). Overall nidus obliteration (achieved in 75% of patients) and morbidity (19%) correlated with lesion size and S-M grade. For S-M Grade I-III AVMs, nonhemorrhagic and hemorrhagic combined, treatment yielded obliteration rates of 100%, 89%, and 86%, respectively; high functional status (Karnofsky Performance Scale Score ≥ 80); and 1% mortality. For S-M Grade IV and V AVMs, outcomes were less favorable, with obliteration rates of 54% and 0%, respectively. The AVMs that were not obliterated had a mean reduction in nidus volume of 69% (range 35%-96%). On long-term follow-up, 10% of patients experienced hemorrhage/rehemorrhage (6% mortality rate), which correlated with lesion size and S-M grade; the mean interval to hemorrhage was 81 months. CONCLUSIONS For patients with S-M Grade I-III AVMs, SRS offers outcomes that are favorable and that, except for the timing of obliteration, appear to be comparable to surgical outcomes reported for the same S-M grades. Staged-dose SRS results in lesion obliteration in half of patients with S-M Grade IV lesions.

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.

Effect of postoperative radiotherapy on the development of small, bowel obstruction in patients undergoing staging laparotomy for Hodgkin's disease

TWO HUNDRED AND TEN PREVIOUSLY UNTREATED PATIENTS WITH HODGKINS DISEASE underwent staging laparotomy at one institution. Medical records of these patients were retrospectively reviewed. The incidence of small bowel obstruction (SBO); whether or not the patient received abdominal radiotherapy and the portals used; whether or not the patient had undergone a previous operation for unrelated disease; and the outcome of operative treatment for the SBO were noted. Mean follow-up for all patients was 62.6 months (1 to 125 months). Ninety-two patients (Group I) were treated without radiotherapy; two developed SBO (2.2%). Patients treated with abdominal radiotherapy numbered 118 (Group II); seven developed SBO (5.9%). The difference between Groups I and II is not significant. Eighty-two received only paraaortic radiotherapy; two (2.4%) developed SBO. Thirty-six patients underwent combined paraaortic and bilateral iliac radiotherapy (Group IV); five developed SBO (13.9%). Data for Groups III and IV approach statistical significance (p = 0.053; Fisher Exact Test [two-Tail]). All obstructions were secondary to adhesions. Four patients in Group IV had significant morbidity associated with operative treatment of SBO. This was an infection in each case. Infections developed in these patients even when the bowel was not entered. Pneumonia and wound infections were most common. Careful evaluation postoperatively for signs of infection and aggressive pulmonary toilet are recommended.

The effect of user-defined variables on dosimetry consistency in Gamma Knife planning.

We report a dosimetric variation caused by a user-defined variable for the Leksell Gamma Knife planning system. Treatment plans of 31 randomly selected patients were studied retrospectively to determine the dosimetric effects in the dose prescription and computation as a result of dose matrix positioning in the Leksell Gamma Plan (LGP, Version 4.12). Phantom studies with ion chamber measurements were carried out to validate the accuracy of the computation results. An average overdose of 2% was found due to the variations in the user-defined dose matrix position for the studied cases. In the extreme, the overdose value was as high as 5% with an over-treatment time exceeding 2 min. The phantom measurements were found to agree with the LGP calculation within 0.5%. An adaptive method was developed and demonstrated in this study to eliminate such dosimetry variations.

A phase I/II trial of whole-abdominal plus pelvic irradiation for Astler-Coller stage beta 2, C colorectal cancer.

From 1982 to 1986, after radical surgery (S) for carcinoma of the rectum and rectosigmoid colon, 25 consecutive patients were entered into a Phase I/II study exploring adjuvant radiation (RT). The latter was given with a single fraction of whole abdomen (mid-body) irradiation (MBI), followed by conventional whole pelvis irradiation (WPI). The minimum follow-up time was 12 months, and the maximum was 44 months. There was escalation of the single MBI dose: 5 Gy in 11 patients, 6 Gy in two patients, and 8 Gy in 10 patients. The 2-year survival rate has been 100 and 45% for Stages B2 and C patients. Only 1/7 Astler-Coller Stage B2 patients failed; this failure was in the lungs. Seven of 15 patients with Stage C failed: one locally, three in the liver, and three in the lungs. Single MBI doses > 5 Gy have yielded a high incidence of intestinal obstruction when combined with routine WPI. Consequently, this combination requires both some modification and careful attention if used in future trials exploring new treatment approaches for colorectal cancer.