A single-institutional experience with low dose stereotactic body radiation therapy for liver metastases.

AIM: This study reports a single-institutional experience treating liver metastases with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: 107 patients with 169 lesions were assessed to determine factors predictive for local control, radiographic response, and overall survival (OS). Machine learning techniques, univariate analysis, and the Kaplan-Meier method were utilized. RESULTS: Patients were treated with a relatively low median dose of 30 Gy in 3 fractions. Fractions were generally delivered once weekly. Median biologically effective dose (BED) was 60 Gy, and the median gross tumor volume (GTV) was 12.16 cc. Median follow-up was 7.36 months. 1-year local control was 75% via the Kaplan-Meier method. On follow-up imaging, 43%, 40%, and 17% of lesions were decreased, stable, and increased in size, respectively. 1-year OS was 46% and varied by primary tumor, with median OS of 34.3, 25.1, 12.5, and 4.6 months for ovarian, breast, colorectal, and lung primary tumors, respectively. Breast and ovarian primary patients had better OS (p < 0.0001), and lung primary patients had worse OS (p = 0.032). Higher BED values, the number of hepatic lesions, and larger GTV were not predictive of local control, radiographic response, or OS. 21% of patients suffered from treatment toxicity, but no grade ≥3 toxicity was reported. CONCLUSION: Relatively low-dose SBRT for liver metastases demonstrated efficacy and minimal toxicity, even for patients with large tumors or multiple lesions. This approach may be useful for patients in whom higher-dose therapy is contraindicated or associated with high risk for toxicity. OS depends largely on the primary tumor.

Stereotactic radiosurgery for the treatment of bulky spine metastases.

INTRODUCTION: Stereotactic radiosurgery (SRS) has shown durable local control for the treatment of metastatic diseasespinal metastases. Multilevel disease or epidural or paraspinal involvement present challenges to achieving local control, and this study aims to analyze treatment outcomes for such lesions. METHODS: Patients treated at a single institution with SRS to the spine from 2010-2018 were retrospectively reviewed. Inclusion criteria required clinical follow-up with either a pain assessment or imaging study. Bulky spine metastasis was defined as consisting of multilevel disease or epidural or paraspinal tumor involvement. RESULTS: 54 patients treated for 62 lesions met inclusion criteria. 42 treatments included at least two vertebrae, and 21 and 31 had paraspinal and epidural involvement, respectively. Treatment regimens had a median 24 Gy in 3 fractions to a volume of 37.75 cm3. Median follow-up was 14.36 months, with 5 instances (8%) of local failure. Median overall survival was 13.32 months. Pain improvement was achieved in 47 treatments (76%), and pain improved with treatment (p < 0.0001). Severe pain (HR = 3.08, p = 0.05), additional bone metastases (HR = 4.82, p = 0.05), and paraspinal involvement (HR = 3.93, p < 0.005) were predictive for worse overall survival. Kaplan-Meier analysis demonstrated that prior chemotherapy (p = 0.03) and additional bone metastases (p = 0.02) were predictive of worse overall survival. Grade < 3 toxicity was observed in 19 cases; no grade ≥ 3 side effects were observed. CONCLUSIONS: SRS can effectively treat bulky metastases to the spine, resulting in improvement of pain with minimal toxicity. Severe pain independently predicts for worse overall survival, indicating that treatment prior to worsening of pain is strongly recommended.

Stereotactic Body Radiation Therapy for Salvage Treatment of Recurrent Non-Small Cell Lung Cancer.

PURPOSE: This study analyzes the outcomes and toxicity of stereotactic body radiation therapy (SBRT) as salvage treatment for recurrent non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: This retrospective analysis considered patients treated with thoracic SBRT and a history of prior external beam radiation therapy (EBRT), SBRT, or surgical resection for NSCLC. Follow-up included positron emission tomography and computed tomography imaging at 2- to 3-month intervals. Key outcomes were presented with the Kaplan-Meier method. RESULTS: Forty patients with 52 treatments were included at a mean of 11.82 months after treatment with EBRT (n = 21), SBRT (n = 15), surgical resection (n = 9), and SBRT after EBRT (n = 7). Median imaging and clinical follow-up were 13.39 and 19.01 months, respectively. SBRT delivered a median dose of 40 Gy in 4 fractions. Median biologically effective dose (BED) was 79.60 Gy. Median gross tumor volume and planning target volume were 10.80 and 26.25 cm3, respectively. Local control was 65%, with a median time to local failure of 13.52 months. Local control was 87% after previous SBRT but only 33% after surgery. Median overall survival was 24.46 months, and median progression-free survival (PFS) was 14.11 months. Patients presenting after previous SBRT had improved local control (P = .021), and the same result was obtained including patients with SBRT after EBRT (P = .0037). Treatments after surgical resection trended toward worse local control (P = .061). Patients with BED ≥80 Gy had improved local PFS (P = .032), PFS (P = .021), time without any treatment failure (P = .033), and time to local failure (P = .041). Using the Kaplan-Meier method, BED ≥80 Gy was predictive of improved local PFS (P = .01) and PFS (P < .005). Toxicity consisted of 10 instances of grade <3 toxicity (16%) and no grade ≥3 toxicity. CONCLUSIONS: Salvage treatment for recurrent NSCLC with SBRT was effective and well tolerated, particularly after initial treatment with SBRT. When possible, salvage SBRT should aim to achieve a BED of ≥80 Gy.

Phase I/II trial of superselective arterial 5-FU infusion with concomitant external beam radiation for patients with either anaplastic astrocytoma or glioblastoma multiforme.

From August 1987 through September 1989, 25 patients with either anaplastic astrocytoma (8 patients) or glioblastoma multiforme (17 patients) were entered into a Phase I trial of combined intra-arterial 5-fluorouracil (5-FU) and external beam radiation therapy. The intra-arterial 5-FU was given in a superselective, supraopthalmic fashion, in escalating doses from 200 mg to 600 mg on a weekly basis during the radiotherapy. Each patient received from 1-4 courses of 5-FU. Radiotherapy consisted of 5,000 rads in 25 fractions given to partial brain fields including the mass and surrounding edema plus a 3-cm margin as defined by computed tomography scan. There were a total of 4 significant acute complications out of a total of 70 infusions. These included 3 ischemic events of which 2 were transient. In addition, 1 patient experienced a cerebral bleed. No patients developed ocular complications. Electroencephalograms (EEGs) were performed immediately before and during 21 intra-arterial infusions. Two patients developed significant EEG changes during intra-arterial infusion, and both of these patients experienced untoward reactions. The remaining patients showed no EEG changes during their infusions. The median survival for patients with glioblastoma multiforme was 15 months. We believe the toxicity of superselective intra-arterial 5-FU infusion combined with external beam radiotherapy is acceptable. This type of treatment deserves further study.

Curative radiotherapy in non-small cell carcinoma of the lung.

Recent reports suggest radiotherapy administered to the 5000-6000 cGy level can result in significant long-term survival in non-small cell carcinoma of the lung. This is particularly true for many cases that are technically operable but for medical or other reasons thoracotomy cannot be performed. Such patients drawn from Southern Appalachia where the principal industry is coal mining are the subject of this report. In this region coal miners pneumoconiosis (black lung) is common as well as other chronic respiratory disorders resulting in poor tolerance for surgery. Three hundred and eleven cases of non-small cell carcinoma were irradiated during the 4 years of 1980 through 1983. This group consisted of 77 patients with clinical Stage T1, T2, T3 all N0, M0 tumors, the majority of which were technically operable but upon whom no thoracotomy was performed because of medical reasons or patient refusal. All are available for 5-year study. Each of these patients was uniformly irradiated to 6000 cGy target dose in 30 fractions over 6 weeks using standard techniques. Absolute or crude survival in these 77 patients is as follows: 1 year, 57%; 2 year, 36%; 3 year, 21%; 4 year, 17%; and 5 year, 17%. Comparison with reported surgical series treated for cure show little difference in survival up to 2 years. Thereafter, the survival curves diverge with radiotherapy patients dying at a somewhat higher rate although by 4 years both survival curves slope similarly. A possible explanation for this difference is the advantage thoracotomy offers in early case selection allowing exclusion of advance cases from surgical reports whereas radiotherapy must include patients with occult local metastasis not identifiable on clinical grounds. This experience, among other reports include evidence that radiotherapy can result in long-term survival or cure with minimal morbidity in lung cancer patients in whom surgery carries excessive risk.

A phase I-II trial of multimodality management of bulky gynecologic malignancy. Combined chemoradiosensitization and radiotherapy.

Between December 1983 and December 1987, there were 44 patients with bulky, nonresectable squamous cell carcinomas of the gynecologic tract (cervix, 36; vagina, eight) who were treated with concomitant chemotherapy and radiotherapy. Chemotherapy consisted of 5-fluorouracil (5-FU) 1g/m2 given by continuous intravenous infusion on days 1 through 4 and mitomycin C 10 mg/m2 given intravenously on day 1. External-beam irradiation was started on day 1 with a total calculated dose of 5000 cGy in 25 fractions employed. This was followed by brachytherapy. With a mean follow-up of 30.3 months and a median of 28 months, local control has been achieved in 32 of 44 patients (73%). The overall response rate was 88% (3-month partial response, 43%; 3-month complete response, 45%; 8-month partial response, 15%; 8-month complete response, 73%). Analysis of complications by Radiation Therapy Oncology Group (RTOG) criteria did not demonstrate an increase in acute or late complications.

Primary malignant extragonadal germ cell tumors. An analysis of the effect of the effect of radiotherapy.

A retrospective analysis was performed on all patients diagnosed with biopsy-proven extragonadal germ cell tumors at the University of Virginia (Charlottesville, VA), The Medical University of South Carolina (Charleston, SC), the Bethesda Naval Hospital (Bethesda, MD), and The Medical College of Virginia (Richmond, VA) for the time period of January 1965 to December 1984. A total of 54 patients were treated with the initial sites of presentation observed: mediastinum, 26; central nervous system, 14; retroperitoneum, eight; and sacrococcygeal region, six. Megavoltage irradiation was used in 44 patients with a dose range of 2400 to 5580 cGy (mean, 4213 cGy). With a minimum follow-up of 4.0 years and a mean follow-up of 10.8 years, the 5-year actuarial survival for the entire population was 57.8%. Local control was achieved in 26 of 44 (59%) of the irradiated population. Factors of prognostic significance included histologic type at presentation, site of presentation, and radiation doses greater than or equal to 4000 cGy. Radiotherapy appears to be an effective modality in patients with extragonadal seminomas; however, the nonseminomatous tumors do not appear to be as radioresponsive.

Early glottic carcinoma: patterns and predictors of relapse after definitive radiotherapy.

Although definitive radiotherapy in the management of early glottic carcinomas continues to offer excellent control, a small proportion of patients will have relapse. Between January 1972 and December 1984, 148 patients with squamous cell carcinoma of the glottis (stage I in 95 patients and stage II in 53 patients) had definitive radiotherapy at the University of Virginia Medical Center. We retrospectively analyzed patient data in an attempt to identify patients at risk for relapse and the patterns of failure. The three-year determinate survival for the entire population was 94.5% (stage I--100%, stage II--86%). Twenty of the 148 patients (14%) had relapse after radiotherapy. Failure in the primary site alone was observed in 17 patients (11%), two patients (1%) had relapse in the lymphatics of the neck without evidence of primary recurrence, and one patient (0.7%) had both neck and distant disease. Of the 19 patients who had definitive surgery after recurrence, 13 (68%) were successfully salvaged. Multivariate analysis was done to identify independent factors on relapse and survival. Statistically significant factors included persistent hoarseness after radiotherapy (P = .00005), impaired cord mobility (P = .00002), subglottic extension (P = .02), anterior commissure extension (P = .001), and multifocal involvement in stage I disease (P = .0008). We conclude that a majority of the small patient population with recurrent glottic carcinoma after radiotherapy may be salvaged with surgery, and we have identified patients at increased risk for recurrence.

Definitive radiotherapy in the management of stage I and II carcinomas of the glottis.

Definitive radiotherapy for early glottic carcinoma continues to offer excellent control and the advantage of voice preservation. In the 13 years from January 1972 through December 1984, there were 187 patients diagnosed with squamous cell carcinoma of the glottis at the University of Virginia Medical Center. One hundred forty-eight patients were treated with definitive radiotherapy as the initial management. The 3-year disease-free survival for the irradiated population was 93.6% in stage I and 75.5% in stage II. Twenty patients had recurrences following radiotherapy, and 13 of 20 were successfully surgically salvaged for an overall determinate survival of 100% in stage I and 85.7% in stage II at 3 years. These statistics are comparable to those from our previous 16-year review of 147 patients from 1956 through 1971. Factors of prognostic significance were persistent hoarseness after radiotherapy, impaired cord mobility, subglottic extension, and multiple sites of involvement in stage I. We conclude that definitive radiotherapy offers excellent survival and that a majority of the small number of treatment failures can be managed with surgical salvage.

Concomitant 5-fluorouracil, mitomycin-C, and radiotherapy for advanced gynecologic malignancies.

Advanced gynecologic neoplasms continue to pose major therapeutic problems; 22,500 deaths were estimated for 1987. Between December 1983 and October 1985, there were 25 patients evaluated at our institution who on joint evaluation by the radiation oncologist and gynecologic oncologists were found to have extensive disease not amenable to standard therapy. Patients were to be treated by a combined modality approach with Mitomycin-C and 5-Fluorouracil given concomitantly with radiotherapy. Nineteen patients were treated definitively and six patients were treated with palliative intent (24 primary, 1 recurrent). The patients ranged in age from 27 to 90 years with a mean of 57.3 and a median of 57. Primary sites at presentation were: cervix--14 patients, vagina--7 patients, and vulva--4 patients. The initial FIGO stages at time of the initial diagnosis were: Stage I--1 (recurrent), Stage II--4, Stage III--15, and Stage IV--5. Chemotherapy consisted of 5-fluorouracil 1 gm/m2 given continuous infusion for 4 days with Mitomycin-C 10 mg/m2 IV push on day 1. Radiation therapy was started on day 1. Only 2 of 25 patients (8%) required chemotherapy reductions. All 25 patients received mega-voltage irradiation. The external beam dose range was 2000-6500 cGy and 14/25 patients received intracavitary or interstitial therapy. In the definitive patient group, there was no reduction in the therapeutic dose. Only four patients underwent surgical therapy. With a minimum follow-up of 8 months and a median follow-up of 28 months, the survival for the entire population was 56%. Fourteen of the 19 patients (74%) treated definitively are surviving with 12 patients having no evidence of disease. Survival by site in the definitive therapy group was cervix--70%, vulva--100%, and vagina--66%. The overall response rate was 84% at 3 and 9 months (3 months; CR--36%, PR--48%, and 9 months; CR--60%, PR--24%). There were no local recurrences in the 12 patients who achieved a complete response. Three patients died of metastatic disease alone and the overall local control was 60%. Evaluation of therapeutic side effects was performed. Hematologic analysis by the Southeastern Oncology Group criteria showed neutropenia in 14 patients (1--life-threatening, 2--severe, and 11 patients--mild/moderate) and thrombocytopenia was observed in 11 patients (all mild or moderate). All hematologic complications resolved. Acute complications did not appear increased except for the addition of mild oral mucositis (12 patients). Six patients demonstrated late effects with only 2 patients felt to have severe complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Whole abdominal radiotherapy following cytoreductive surgery and chemotherapy in ovarian carcinoma.

Persistent or recurrent disease following surgery and chemotherapy in ovarian carcinoma remains a major therapeutic dilemma. Between January 1980 and December 1985, there were 26 patients who had previously undergone cytoreductive surgery and chemotherapy and were treated with external beam radiotherapy. Twenty-one of these patients had been treated with platinum-adriamycin-cytoxan (PAC) regimen and 5 were treated with other combinations. Surgical reevaluation was performed in 21 of the 26 patients and only 4/21 (19%) patients were free of disease. All 26 patients were irradiated with a planned dose of 2500 cGy/100 cGy/day or 2280 cGy/120 cGy/day to the whole abdomen and a final calculated dose to the pelvis of 4500 cGy. Initial evaluation showed a 3-year actuarial survival rate of 51% and a disease-free survival rate of 42%. Follow-up analysis yields survivals of 45 and 35%, respectively. Severe gastrointestinal complications were observed in 3/26 patients and all hematologic complications resolved. Variables of prognostic significance were chemotherapy tolerance, grade, and volume of residual disease. We conclude that a proportion of patients with disease following cytoreductive surgery and chemotherapy may be salvaged with abdominopelvic irradiation.

Primary central nervous system germ cell tumors. Effect of histologic confirmation on radiotherapy.

Primary malignant intracranial germ cell tumors are rare lesions responsible for only 0.5% of all central nervous system (CNS) malignancy. With stereotactic localization these lesions can be safely biopsied, and histologic confirmation will affect the ultimate prognosis. This report is a multi-institutional retrospective analysis of 33 patients diagnosed with a primary CNS germ cell tumor. Tumors in 14 patients (42%) were histologically confirmed (13 germinoma and one embryonal cell carcinoma); 19 patients were treated with a presumptive diagnosis. All patients were irradiated with a dose range of 3950 cGy to 6000 cGy to the primary lesions. Eight patients received craniospinal irradiation, and 25 patients were locally treated. The 5-year actuarial survival for the entire population was 64%. The survival rate in patients with histologic confirmation was 79% versus 53% in the unbiopsied population. Radiation doses greater than 5000 cGy, radiotherapy volume, and age were prognostic factors in determining survival.

Prognostic value of vocal cord fixation with respect to treatment in cancers of the supraglottis and pyriform sinus.

Vocal cord fixation in supraglottic and pyriform sinus cancers has, in the past, precluded management by radiotherapy alone. Ninety-eight patients were reviewed to determine the prognostic effect of vocal cord fixation. The predictive value of cord mobility status after 50 Gy was evaluated with respect to treatment modality. For patients treated with radiotherapy alone, cord mobility status was predictive of recurrence, yielding 3 year recurrence rates of 33.3% (mobile) versus 80% (fixed) [p = 0.04]. Mobile cords after 50 Gy had similar recurrence rates (33.3% vs. 40.0%, p = 0.60) whether treated by radiotherapy or radiotherapy/surgery. Radiotherapy alone may be used in cases when fixed cords become mobile after 50 Gy without compromising cure rates or laryngeal function. Combined modality provides the best results when cords remain fixed.

Primary malignant mediastinal germ-cell tumors and the contribution of radiotherapy: a southeastern multi-institutional study.

A retrospective review was performed by a multi-institutional study group to determine the contribution of radiotherapy to the management of primary malignant mediastinal germ-cell tumors. Twenty-seven patients diagnosed with a primary mediastinal germ-cell tumor between January 1965 and July 1985 form the basis of this study. Twenty-five of the 27 patients were male. Thirteen patients' tumors were diagnosed as seminoma and the remaining 14 patients' tumors had other germ-cell histologies. The single most important prognostic factor was histology, with a 5-year actuarial survival of 100% for the seminomas and only 8.8% for the remaining germ-cell varieties. If total surgical extirpation is not possible, biopsy may be adequate. Of the patients with seminoma, 11 of 12 had local control, and 3 of the 12 patients were treated with doses between 3,000 and 3,100 cGy. High doses for this variety of mediastinal germ-cell tumor might not be required. For the germ-cell tumors other than seminoma, no patient had local control with doses over the range of 3,000-4,750 cGy.

Malignant thymoma: role of radiation therapy in management.

Malignant thymoma is a rare tumor generally seen as an anterior mediastinal mass. Radiation therapy in ten patients with malignant thymoma diagnosed in 1968-1983 was reviewed retrospectively. Surgical therapy consisted of subtotal resection in four patients and biopsy only in six. Megavoltage irradiation in the dose range of 4,600-5,250 cGy was employed. In all symptomatic patients, palliation of presenting symptoms was achieved. In seven patients, a greater than 50% reduction in tumor mass followed radiation therapy. Local control was achieved in six patients. Three patients show no evidence of disease clinically, after a minimum follow-up study of 1 year. Radiation therapy is an important therapeutic modality in the control of malignant thymoma.