Utility of radiation in the prevention of heterotopic ossification following repair of traumatic acetabular fracture.

PURPOSE: Heterotopic ossification (HO) is a common problem following surgical repair of traumatic acetabular fracture (TAF), potentially causing severe pain and decreased range of motion. This report analyzes the role of radiation therapy for prevention of HO in TAF. METHODS AND MATERIALS: The charts of all patients who received RT to the hip following TAF repair between July 1988 and January 1998 were reviewed. Sixty-six patients were identified. RT was given in 5 fractions of 2 Gy in 45 patients, 1 fraction of 8 Gy in 17 patients, and other doses in 4 patients. Treatment fields encompassed periacetabular tissues at highest risk for HO. Time to RT was < or = 24 hours for 46 patients. RESULTS: Radiographic follow-up at least 6 months following RT was available in 47/66 (71%) patients to permit Brooker classification, revealing 6 cases (13%) of Grade III HO, compared to historical incidence in this population of 50%. No Grade IV HO was found. Mean follow-up was 18 months. Four of the Grade III patients had received 10 Gy/5 fractions, and 2 received 8 Gy/1 fraction. Postoperative wound infection occurred in 6 patients, and osteonecrosis of the femoral head was found in 13. CONCLUSIONS: RT following surgical repair of TAF provides effective prophylaxis against formation of clinically significant HO. We recommend a single fraction of 7-8 Gy within 24 hours of surgery to prevent HO formation and minimize patient discomfort.

Superior sulcus (Pancoast) tumor: experience with 105 patients.

BACKGROUND: The evolution of therapy in 105 patients with superior sulcus (Pancoast) tumor over the past 42 years was reviewed. METHODS: There were 82 men and 23 women aged 30 to 75 years. Tumor cell types were: squamous, 41 (39%); adenocarcinoma, 23 (21.9%); anaplastic, 14 (13.3%); undetermined, 12 (11.4%); mixed, 9 (8.7%); and large cell 6 (5.7%). Therapy was based on extent of disease and lymph node involvement. There were 5 treatment groups: I, preoperative radiation and operation (n = 28); II, operation and postoperative radiation (n = 16); III, radiation (n = 37); IV, preoperative chemotherapy, radiation, and operation (n = 11); and V, operation (n = 12). RESULTS: The median survival for group I was 21.6 months; group II, 6.9 months; group III, 6 months; and group V, 36.7 months. Median survival for group IV has not yet been reached (estimated at 72% at 5 years). On univariate analysis, mediastinal lymph node involvement, Horner syndrome, TNM classification, and method of therapy affected survival. On multivariate regression analysis, only N2 and N3 disease and method of therapy were significant (p < 0.05). CONCLUSIONS: The optimal treatment for superior sulcus tumor was preoperative radiation and operation. However, triple modality therapy, although promising, requires longer follow-up.

Fractionated half-body irradiation for pain palliation in widely metastatic cancers: comparison with single dose.

PURPOSE: To explore fractionated half-body irradiation (HBI) for pain palliation and determine if it is more efficient and effective than single dose HBI. METHODS AND MATERIALS: During the last 13 years, 75 out of 115 HBIs (64%) at the University of Maryland Medical Center were given for palliation of various widely metastatic cancers (28% prostate, 25% breast, 12% lung). The HBI fields were 28% upper, 25% mid, and 47% lower; three patients had both upper and lower HBI. An initial performance status (PS) 3&4 with a life expectancy < 3 months was found in 50% of patients. The HBI techniques used on consecutive patients were: single dose (SD) in 54% with escalating doses of 4-10 Gy; split-course (SC) in 12% with two 4 Gy single doses separated by 2 weeks; and daily fractionated (DF) in 34% with five fractions of 3 Gy each. There were 68 of 75 HBI (91%) given for pain control purposes. RESULTS: The percent total (complete) pain relief was SD-73(32), SC-50(13), and DF-96(49). Time to maximum and (complete) relief was: SD 5 days each and DF HBI 7(11) days. Pain-free survival (PFS) was short but so was overall survival (OS). PFS was SD-5, SC-4.5, and DF-19 weeks. The percent of the remaining patient's life spent pain free without retreatment (NPR) was SD-38, SC-34, and DF-68. Differences in pain relief, PFS, OS, and NPR were significant and carried over primary tumor types; prostate, breast, and surprisingly GI were very responsive (90, 84, and 83%, respectively). On multivariate analysis only the PS and degree of relief were independent variables. Despite lack of premedication in DF-HBI, toxic reactions were identical to SD-HBI with premedication. No Grade 4 toxicities occurred. Grade 3 toxicities were 4%. Retreatment was 3% in SD and 13% in fractionated HBI; these differences were not significant. CONCLUSION: HBI is still the most effective and efficient way to palliate pain from widely disseminated cancer. Fractionating HBI eliminates need for the premedication and close patient monitoring required for SD-HBI. It also allows for an increase in total dose which can produce better responses in pain relief, duration of relief, PFS, OS, and quality of life.

Mediastinal lung cancer: answers and questions.

A literature review was done to define the relative roles of radiation and surgery in the treatment of mediastinal stage III, non-small-cell lung cancer with no distant metastasis. No two reports are comparable. Little information is available on the clinical, preoperative stage as it relates to surgical findings and to survival. Rationale for adjuvant radiation is lacking from the reports. There is no survival advantage of surgery, even with postoperative radiation, over radiation alone for clinical stage III disease. Patients whose cancer seems early stage but is found to be pathologic stage III at time of surgery may benefit from the combination therapy, although this is controversial. Treatment failure is usually systemic, so there is a strong argument for adjuvant chemotherapy as well. Uniform multimodality reporting of results is necessary so that the appropriate roles of surgery, radiation, and chemotherapy can be identified for this group of patients.

Radiation therapy for chest recurrences following induction chemotherapy in small cell lung cancer.

Once small cell lung cancer fails induction chemotherapy, second line drugs are usually ineffective, accounting for mostly partial responses in the order of 0-20% and a median survival of 6-10 weeks. A review of patients with relapsed small cell lung cancer was carried out at the University of Maryland. Of 51 such patients, 44 received thoracic irradiation at the time of relapse. Excluding 8 patients who received insufficient treatment, the series consists of 36 patients (27 with limited and 9 with extensive disease) and represents the largest experience with relapsed small cell lung cancer subjected to radiation alone. Total radiation doses were 60 Gy in 11, 45-55 Gy in 14, and 38-42 Gy in the remaining 11 patients. No second line chemotherapy was given simultaneously with radiation at time of relapse and it was only given subsequently during the course of the disease to four patients. Responses to radiation were seen in 28 (77%) with 9 (25%) complete and 19 (52%) partial. The median survival was 16-40 weeks varying with disease extent, response, and total dose. Subsequent failures occurred in chest (34%) and distant sites (66%). A dose-response curve was attempted; the higher doses achieved as much as 75% local control. A poor response to induction chemotherapy did not predict a poor radiation response at time of relapse. Nearly 2/3 of patients who had not responded to induction chemotherapy responded to radiation at the time of relapse. The post-recurrence survival after radiation therapy was as long as or longer than the recurrence-free interval after induction chemotherapy, and this clearly demonstrates the value of radiation in achieving excellent palliation and good quality of life in these patients. Thoracic irradiation is recommended as a therapeutic alternative for locally recurrent small cell lung cancer after induction chemotherapy.

A protocol for the safe administration of debrisoquine in biochemical epidemiologic research protocols for hospitalized patients.

The genetically determined ability to metabolize the antihypertensive drug debrisoquine has been proposed as a genetic risk factor for primary carcinomas of the lung. To test this hypothesis, the metabolism of the drug was evaluated in a case control study. The subjects were characterized by their ability to metabolize debrisoquine after receiving a test dose of the drug followed by the collection of an 8-hour urine sample. They were classified by laboratory analysis into one of the following three groups: extensive, intermediate, and poor metabolizers. Poor metabolizers comprise 10% of the population and are unable to hydroxylate the drug. This group was expected to be at highest risk for deleterious effects from this medication. A protocol was created that included patient education and blood pressure monitoring to administer this medication safely to a group of patients with cancer who were already compromised. Although poor metabolizers showed a small decrease in systolic and diastolic blood pressure, no significant hypotensive episodes or clinical sequelae were observed in any of the groups. These data suggest that debrisoquine can be administered safely in a controlled clinical setting and will be useful for the characterization of lung cancer patients in biochemical epidemiology studies.

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.

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 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 greater than 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.

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.

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 hodgkin's 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.

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.

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.

Value of prophylactic cranial irradiation given at complete remission in small cell lung carcinoma.

The optimal use of "prophylactic" cranial irradiation (PCI) in patients with small cell lung cancer remains undetermined. This study reviews the impact of PCI, given at complete remission (CR), on neurologic relapse in 172 consecutive patients with small cell lung cancer treated in three sequential chemotherapy protocols at the University of Maryland Cancer Center. In the first study of 38 patients, none received PCI. In the second study of 109 patients, the first 28 achieving CR were randomized to 3000 rad of PCI in ten fractions (PCI+) or to observation (PCI-). Thereafter, based on interim analysis, all patients achieving CR received PCI. In the third study, to date, 25 patients achieving CR have received PCI. Overall, 169 patients were evaluable for neurologic relapse, and 30 of 90 patients achieving CR received PCI. Among all patients with CR, with adjustment for disease extent, there was a significant delay to any neurologic relapse (P = 0.01) and cerebral metastases (P = 0.02) for PCI+ compared to PCI- patients. Among PCI- patients with CR, cerebral metastases alone occurred in 28% as the sole site and in 33% as the initial site, whereas cerebral relapse occurred prior to systemic relapse in only one PCI+ patient with CR. Patient survival however, was not significantly altered by PCI. PCI at CR confers effective and worthwhile local control in the CNS, especially during periods of systemic response, and a small percentage of patients may benefit. Systemic drug resistance still determines overall survival.

Long-term cardiovascular evaluation of patients with Hodgkin's disease treated by thoracic mantle radiation therapy.

The long-term cardiac effects of anterior-weighted thoracic mantle field radiotherapy were assessed in 25 patients treated for Hodgkin's disease. These patients underwent an evaluation that included a careful history and physical examination, ECG, M-mode echocardiogram, exercise ECG-gated radionuclide ventriculography, and cardiac catheterization. In these 25 patients evaluated 37-144 months (median, 96) after completion of thoracic mantle radiotherapy, eight had constrictive pericarditis; eight had occult constrictive pericarditis; three had an abnormal response to fluid challenge; three had suspected or proven occlusive coronary artery disease; and one each had a cardiomyopathy and diminished functional capacity on exercise testing. Only one patient appears to be normal after evaluation. The clinical spectrum of delayed-appearing radiation-induced cardiac disease in patients treated by anterior-weighted thoracic mantle fields and our suggestions for its treatment are discussed.

Hodgkin's disease with direct extension into pulmonary parenchyma from a mediastinal mass: a presentation requiring special therapeutic considerations.

The significance of limited extranodal Hodgkin's disease involving pulmonary parenchyma by direct extension from a mediastinal mass (E stage) was evaluated in 177 patients with stages IA-IIIB. Disease-free and total survival rates of four groups were compared: 58 patients without and 13 patients with pulmonary E stage treated with radiotherapy followed by six courses of MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), and 86 patients without and 20 patients with E stage treated with radiotherapy alone. The 12-year disease-free and total survival rates projected by life-table analysis were significantly poorer for E stage patients treated with radiotherapy alone. It is concluded that pulmonary E stage requires special therapeutic considerations if end results are to equal those obtained with standard radiotherapy for Hodgkin's disease confined to lymph nodes, and that combined modality therapy is one method by which pulmonary E stage may be treated successfully.

The late appearance of chronic pericardial disease in patients treated by radiotherapy for Hodgkin's disease.

Radiation-induced chronic pericardial disease was recognized in nine patients 53 to 124 months (mean, 88 months) after radiotherapy for Hodgkin's disease. Depending on whether abnormal cardiac hemodynamics occurred before or after a fluid challenge, patients were considered to have either constrictive pericarditis (Group I) or occult constrictive pericarditis (Group II). There were no differences between these groups in various radiotherapy data, the use of chemotherapy, or the interval after treatment when the diagnosis of chronic pericardial disease was made. There were no consistent noninvasive variables to support the diagnosis of radiation-induced chronic pericardial disease before cardiac catheterization. Four patients underwent pericardiectomy. Two of the four operated patients had an excellent surgical result; a third patient died 4 months postoperatively of drug-induced granulocytopenia; the fourth patient has persistent visceral constrictive pericarditis 18 months after surgery. Speculation over the causes of radiation-induced chronic pericardial disease is made and our recommendations for its treatment given.

Delayed pericardial disease after radiotherapy.

Delayed chronic constrictive pericarditis developed in seven patients 51 to 268 (mean 116) months after radiotherapy. Six of the seven complained of exertional dyspnea that was initially believed to be caused by mediastinal fibrosis. All patients had raised jugular venous pressure, although in two patients this finding was not appreciated by the primary physician. There were no consistent noninvasively identifiable features to allow prediction of constrictive pericarditis other than consideration of its existence and careful examination of the cardiovascular system. All patients had constrictive pericarditis proved at cardiac catheterization. Of the five patients who underwent pericardiectomy, two had an excellent functional result, one has residual pericardial constriction and two died of unrelated causes. Recommendations for the treatment of radiation-induced pericardial disease are given.

Radiation therapy for patients with asymptomatic lung cancer.

The usefulness of thoracic irradiation was evaluated in 62 patients with asymptomatic Stage III carcinoma of the lung. In 48 patients, the disease was confined to the thorax, in eight supraclavicular nodes were involved, and in six there were distant metastases. Fourteen patients were in poor general conditions as well. Fourteen patients received a short course of irradiation (less than 3,000 rad [30 Gy]), while 48 received radical doses (5,500-6,000 rad [55-60 Gy]). Five patients (8%), all with carcinoma confined to the thorax, survived three years. Radical radiation therapy plays a positive role in the treatment of asymptomatic State III carcinoma of the lung, and may result in tumor control in those patients with no extrathoracic disease.