Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review.

PURPOSE: This study reports clinicopathological features and outcome of thymic tumors. Twenty-seven patients with invasive thymoma and 6 patients with thymic carcinoma who had received radiotherapy either primary or postoperatively were analyzed retrospectively. PATIENTS AND METHODS: All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) or biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. RESULTS: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77.4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p = 0.04). Considering local control, radiation dose was a significant prognostic factor (p = 0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5-year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p = 0.007) and DFS (p = 0.0007). CONCLUSION: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival.

A quality assurance program in stereotactic radiosurgery using the Gamma Knife unit.

Because of the large single-fraction dose in stereotactic radiosurgery it is important to guarantee a high geometric and dosimetric accuracy. The paper represent the quality assurance program for the Gamma Knife unit at the University Clinic of Neurosurgery in Graz. The program includes the following procedures: timer control, mechanical radiation isocenter coincidence, trunnion centricity, helmet microswitches test, radiation output and relative helmet factors, dose profile verification, safety interlocks checks and software quality assurance. In summary, the mechanical accuracy and reproducibility of the Gamma Knife unit are < 1 mm. The geometric failure in stereotactic Gamma Knife treatment is limited by the human error in setting the clinical target volume and the spatial accuracy of dose delivery to the patient is limited by the accuracy of modern target localization procedures.

Prognostic factors in patients with carcinoma of the uterine cervix treated with external beam irradiation and IR-192 high-dose-rate brachytherapy.

PURPOSE: Prognostic factors in cancer of the cervix for patients treated with external beam irradiation (EBR) and low-dose-rate (LDR) brachytherapy have been characterized. However, despite the increasing use of high-dose-rate (HDR) intracavitary placements (ICP), few studies with adequate follow-up have analyzed prognostic factors. This study investigates pretreatment and treatment factors for their correlation with treatment outcome after EBR and HDR-ICP. METHODS AND MATERIALS: Between September 1985 and December 1994, 181 patients with carcinoma of the cervix FIGO stages IB-IV received EBR and HDR brachytherapy. Hemoglobin (Hb) levels were maintained above a level of 11 g/dl during the treatment by transfusion. Patient age ranged from 34 to 84 years (median: 66). The median follow-up time for patients at risk is 69 months (range: 23-140). Pretreatment and treatment parameters analyzed to determine their prognostic value included age, FIGO stage, tumor size, tumor type and grade, pretreatment Hb level, number of HDR-ICP, total dose from HDR-ICP, overall dose to point A, and overall treatment time. Also evaluated was the prognostic value of enlarged lymph nodes noted on pretreatment CAT scan of the abdomen and pelvis. Endpoints studied in uni- and multivariate analyses were disease-specific survival (DSS), freedom from disease (FFD), pelvic control (PC), and probability of distant metastases (DM). RESULTS: At 5 years the DSS, FFD, and PC rates for all patients were 60%, 58%, and 67%, respectively. The 5-year FFD by stage was: IB: 94%; II: 63%; IIIB: 43%; and IV: 0%. The PC rates were 94%, 66%, 59%, and 0%, respectively. In univariate analysis the prognostic factors identified for FFD were FIGO stage, tumor size, initial Hb level, and enlarged pelvic and/or paraaortic nodes (all: p < 0.0001). Age was inversely correlated with outcome (p = 0.0081). The 5-year FFD rates for tumors (< 3, > or = 3 < 6, > or = 6 cm) were 97%, 65%, and 24%; patients with initial Hb levels < or = 11g/dl had a FFD of 26% versus 69% for patients with levels > 11g/dl; and those with pelvic and/or paraaortal nodes > or = 1 cm had a survival of 32% versus 68% in patients with negative readings. The same factors were also prognostically significant for DSS, PC, and DM. Patients with persistent disease or pelvic failures had a significantly higher incidence of DM than patients in whom pelvic disease was controlled (p < 0.0001).Histological and treatment parameters including overall treatment time were not of prognostic significance for any of the endpoints studied. In multivariate analysis tumor size was the most powerful parameter for DSS, FFD, PC (p < 0.0001) and DM (p = 0.0001), followed by low initial Hb level (DSS: p = 0.0004, FFD: p = 0.0009, PC: p = 0.0012, DM: p = 0.0265), and enlarged pelvic and/or paraaortic nodes which were predictive for DSS (p = 0.0210) and DM (p = 0.0011). CONCLUSION: This study confirms that prognostic factors for patients treated with HDR brachytherapy are similar to those reported in previous series that employed LDR brachytherapy. The significance of tumor size, pretreatment Hb level, and enlarged pelvic and/or paraaortic lymph nodes on CAT scan over FIGO stage of disease were demonstrated. Future prospective trials should be undertaken to confirm the validity of these factors and to elucidate their therapeutic implications.

Postoperative radiotherapy in radically resected non-small cell lung cancer.

PURPOSE: To evaluate the value of adjuvant postoperative external-beam radiation (EBR) in patients with radically resected non-small cell lung cancer (NSCLC) pT1-3 pN0-2 compared to patients with resected NSCLC without adjuvant EBR. MATERIALS AND METHODS: In 155 patients (121 male, 34 female; mean age, 59 years) 105 lobectomies, 12 bilobectomies, and 38 pneumonectomies with radical lymph node dissection of the contralateral [corrected] side were performed. Postoperative staging was done according to the TNM system and was as follows: pT1 (n=38), pT2 (n=89), pT3 (n=28); pN0 (n=39), pN1 (n=67) and pN2 (n=49). Histopathologic study revealed 68 squamous cell carcinomas, 53 adenocarcinomas, 21 large cell carcinomas, 6 adenosquamous cell carcinomas, and 7 bronchioloalveolar cell carcinomas. All patients were randomly assigned into two treatment groups: 72 patients with no further treatment (control group), and 83 patients (EBR group) with adjuvant postoperative EBR of the bronchial stump and mediastinum (50 to 56 Gy, 8 or 23 MV photons, 2 Gy/d, 5 d/wk) beginning 4 to 6 weeks after surgery. RESULTS: The overall 5-year survival rate (median observation time, 43 months) of all patients was 24.1% (EBR group, 29.7%; control group, 20.4%; p>0.05, not significant). The relative risk of the EBR group was 0.85 with a two-sided confidence interval of 0.66 to 1.09. The overall 5-year recurrence-free survival was 20.6% (EBR, 27.1%; control group, 15.6%; p=0.07). The relative risk of the EBR group was 0.80 with a confidence interval of 0.63 to 1.01. The rate of local recurrences at the bronchial stump and/or mediastinum was significantly smaller in the EBR group (n=5) than in the control group (n=17) (p<0.01). Multivariate analysis (chi2 test) demonstrated an independent influence of postoperative EBR on the incidence of local recurrences. The incidence of distant metastases was slightly but not significantly higher in patients without EBR (38 patients) compared to those who had EBR (32 patients). CONCLUSION: High-dose postoperative EBR to the mediastinum significantly reduces the risk of local recurrence at the bronchial stump and/or mediastinum. Age, sex, histologic subtype, tumor size, surgical approach, or extent of lymph node involvement had no prognostic value--only postoperative EBR had an independent influence on the risk of local recurrence. The effect of postoperative EBR was on the verge of significance with respect to recurrence-free survival and showed the same tendency in overall survival, however with an attenuated relative risk.

Carcinoma of the cervix: analysis of complications after primary external beam radiation and Ir-192 HDR brachytherapy.

BACKGROUND AND PURPOSE: There is still a concern that the use of HDR brachytherapy might result in an increase of late tissue damage. This restrospective study evaluates the incidence and severity of late complications in patients with carcinoma of the cervix who underwent combined external beam radiation (EBR) and Ir-192 HDR brachytherapy and attempts to identify pretreatment and treatment parameters correlating with late complications. MATERIAL AND METHODS: Between 1985 and 1992, 161 patients with carcinoma of the cervix (FIGO stages IB-IVB) received EBR to the pelvis (ave, max. dose 48.8 Gy) followed by 1-6 Ir-192 HDR placements (median 2). Doses to point A ranged from 8.5 to 38.7 Gy (median 17 Gy). Parameters examined included age, diabetes, obesity, history of inflammatory bowel disease or diverticulitis, prior surgery, hemoglobin level, FIGO stage, EBR dose, technique and daily dose fraction, number of HDR treatments and total dose to point A, maximum doses to bladder and rectum delivered by brachytherapy and cumulative dose to point A. Median follow-up for all patients was 37 months. Complications were rated using an in-house scoring system and according to the French-Italian Glossary (FIG). RESULTS: Actuarial 5-year survival was 93%, 57%, 46%, and 0% for stages IB, II, IIIB, and IV, respectively. Of 161 patients, 11% developed moderate and 3.7% severe sequelae (FIG: 2.5%, 3.7%). Since some patients experienced more than one complication, the overall incidence was 13.6% and 4.9% (FIG: 3.1%, 4.9%) with respective 5-year actuarial rates of 14% and 5% for moderate, and 2% and 8% for severe bowel and genitourinary tract complications (FIG: 3.5%, 0, and 2%, 8%). All severe bowel complications occurred within 1.5 years whereas urinary tract sequelae continued to develop throughout the follow-up period. FIGO stage was associated with a significant increase in late sequelae (P = 0.015). Analysis of the remaining pretreatment and treatment parameters failed to reveal any statistically significant correlation with moderate or severe sequelae. CONCLUSION: In our series using HDR brachytherapy, complication and survival rates were comparable with other series employing either LDR or HDR procedures. Of all parameters analysed, stage of disease was the only parameter significantly correlated with complications in univariate and multivariate analysis.

Dosimetry of intracavitary placements for uterine and cervical carcinoma: results of orthogonal film, TLD, and CT-assisted techniques.

A total of 720 192Ir high-dose-rate (HDR) applications in 331 patients with gynecological tumors were analyzed to evaluate the dose to normal tissues from brachytherapy. Based on the calculations of bladder base, bladder neck, and rectal doses derived from orthogonal films the planned tumor dose or fractionation was altered in 20.4% of intracavitary placements (ICP) for cervix carcinoma and 9.2% of ICP for treatment of the vaginal vault. In 13.8% of intracervical and 8.1% of intravaginal treatments calculated doses to both the bladder and rectum were greater than or equal to 140% of the initially planned dose fraction. Doses at the bladder base were significantly higher than at the bladder neck (p less than 0.001). In 17.5% of ICP the dose to the bladder base was at least twice as high as to the bladder neck. The ratio of bladder base dose to the bladder neck was 1.5 (+/- 1.19 SD) for intracervical and 1.46 (+/- 1.14 SD) for intravaginal applications. The comparison of calculated doses from orthogonal films with in-vivo readings showed a good correlation of rectal doses with a correlation coefficient factor of 0.9556. CT-assisted dosimetry, however, revealed that the maximum doses to bladder and rectum were generally higher than those obtained from films with ratios of 1-1.7 (average: 1.44) for the bladder neck, 1-5.4 (average: 2.42) for the bladder base, and 1.1-2.7 (average: 1.37) for the rectum. When doses to the specified reference points of bladder neck and rectum from orthogonal film dosimetry were compared with the corresponding points on CT scans, similar values were obtained for both methods with a maximum deviation of +/- 10%. Despite the determination of multiple reference points our study revealed that this information was inadequate to predict doses to the entire rectum and bladder. If conventional methods are used for dosimetry it is recommended that doses to the bladder base should be routinely calculated, since single point measurements at the bladder neck seriously underestimate the dose to the bladder. Also the rectal dose should be determined at several points over the length of the implant due to the wide range of anatomic variations possible.

Bladder and rectal dose of gynecologic high-dose-rate implants: comparison of orthogonal radiographic measurements with in vivo and CT-assisted measurements.

Bladder and rectal doses were retrospectively reviewed in 281 patients who underwent implantation of 575 gynecologic iridium-192 high-dose-rate devices. Dose measurements obtained with orthogonal radiography, in vivo thermoluminescent dosimetry, and computed tomography (CT)-assisted planning were compared. Measurements of bladder dose derived from radiographs revealed a significant difference between bladder neck dose and bladder base dose (P less than .0001). In 17% of cases, the dose to the bladder base was at least double the dose to the bladder neck. The mean dose to the rectum calculated from radiographs was 85.9% (cervix) and 90.2% (vaginal vault) of the prescribed fraction dose. The correlation coefficient factor between doses determined with orthogonal radiographs and doses determined with in vivo measurements was .9694. The dose to the bladder neck and to four rectal points determined with corresponding CT images revealed a deviation of 4% and 7%, respectively. However, calculations at the rectal wall cephalic to the specified rectal points showed higher doses to the rectum, with a ratio of 1-1.6. CT-assisted calculations at the bladder base also revealed doses that were higher than those obtained with radiographs alone by a ratio of 1.4-2.2. CT-assisted dosimetry is the method of choice.