Course Of External Beam Radiotherapy Research Articles

Endobronchial brachytherapy and optimization of local disease control in medically inoperable non-small cell lung carcinoma: a matched-pair analysis

Purpose External beam radiation therapy (EBRT) alone for early stage, medically inoperable non-small cell lung cancer (MILC) can produce local disease control and sometimes cure. We have previously reported that higher EBRT doses result in improved disease control and, for patients with tumors ≥3.0 cm, improved survival. This report describes the impact of dose escalation with endobronchial brachytherapy boost during or following EBRT upon local disease control. Methods and materials Medical records of 404 patients with MILC treated with radiotherapy alone were reviewed. Thirty-nine patients received a planned endobronchial brachytherapy boost during or following a course of EBRT. A matched-pair analysis of disease control and survival was performed by matching each brachytherapy patient to 2 EBRT patients from a reference group of the remaining patients. Results Endobronchial brachytherapy boost significantly improved local disease control over EBRT alone (58% vs. 32% at 5 years). The local control benefit for brachytherapy was found to be limited to patients with T 1–2 disease or tumors ≤5.0 cm. Among these patients treated with endobronchial boost, EBRT doses of ≥6500 cGy were necessary to optimize local disease control. No overall survival differences were observed at 3 years. Excess toxicity with brachytherapy was not observed. Conclusion Endobronchial brachytherapy boost enhances local disease control rates in MILC treated with EBRT. Local control outcome is optimized when radical EBRT doses are used in conjunction with brachytherapy.

Results of definitive irradiation in a series of 305 epidermoid carcinomas of the anal canal

Purpose To evaluate our data concerning the prognostic factors for locoregional control, survival, late complications, and sphincter conservation in a series of epidermoid cancers of the anal canal without clinical evidence of metastasis. Methods and materials Between June 1972 and January 1997, 305 patients were treated with curative-intent radiotherapy (RT). The T stage according to the 1987 International Union Against Cancer classification was T1 in 26, T2 in 141, T3 in 104, and T4 in 34. Forty-nine patients had nodal involvement at presentation. The pretreatment anal function score, according to our in-house system, was 0 for 22 patients, 1 for 182, 2 for 74, 3 for 7, and 4 for 11 patients; for 9 patients, scores were unavailable. The treatment started with external beam radiotherapy (EBRT) in 303 patients (median dose 45 Gy). After a rest period of 4–6 weeks, a boost of 20 Gy was delivered by EBRT in 279 patients and by interstitial 192Ir brachytherapy in 17 patients. Seven patients received only one course of EBRT (mean dose 49.5 Gy), and 2 patients were treated with interstitial 192Ir brachytherapy alone (55 Gy and 60 Gy). Concomitant chemotherapy (5-fluorouracil and either mitomycin C or cisplatin) was delivered to 19 patients. The mean follow-up was 103 months (median 84). Results At the end of RT, the local tumor clinical complete response rate was 96% for T1, 87% for T2, 79% for T3, and 44% for T4. Of the 61 locally progressive tumors, 27 (44%) were salvaged with abdominoperineal resection. The rate of local tumor relapse was 12%. Among 37 local tumor relapses, 20 (54%) were salvaged with abdominoperineal resection and one with interstitial 192Ir brachytherapy. The overall local control rate (with or without salvage local therapy) was 84%. The local control rate with good anal function (score 0 or 1) was 56.5%. Of 181 available patients with their anus preserved, 94% had good anal function. For a subgroup of 15 patients with a tumor length of <2 cm and without nodal involvement, the clinical complete response rate after RT completion was 100%, the local control rate with or without local salvage treatment was 100%, and among 13 available patients with their anus preserved, the anal function score was good in 12 patients (92%). The 10-year disease-free survival rate was 74%. After multivariate analysis, three independent predictive factors significantly influenced disease-free survival: the interval between the two courses of RT (>38 days vs. ≤38 days, p = 0.0025), pretreatment anal function score (0 vs. 1 vs. 2 vs. 3 vs. 4, p = 4.4.10 −6), and clinical complete response after RT completion (no complete response vs. complete response, p = 2.5.10 −14). Conclusion We confirm the excellent results with RT in T1 and T2 lesions. However, to improve survival without colostomy with good anal sphincter function, chemoradiotherapy should be preferred for tumors ≥2 cm in length and for locally advanced tumors.

Results of high dose rate afterloading brachytherapy boost to conventional external beam radiation therapy for initial and locally advanced prostate cancer.

To evaluate the impact on biochemical control (bNED), acute and late gastro-intestinal (GI) and urological (GU) morbidity of initial and locally advanced prostate cancer treated with fractionated transrectal ultrasound-guided (TRUS) high dose rate after loading brachytherapy (HDR-B) as a boost to conventional external beam radiation therapy (EBRT). From March 1997 to February 2000 a total of 119 patients with any of the following characteristics were eligible for study entry: biopsy proven adenocarcinoma Gleason scored (GS), initial prostatic specific antigen (PSA) level dosage 1992 AJCC clinical stage T3a or less, and prostatic volume <60 cc. All patients had prior to HDR-B a course of EBRT 6 MV photons to a median dose of 45 Gy, in 1.8 Gy fractions, to the prostate and seminal vesicles only. HDR-B treatment planning and dosimetric calculations were generated with the Nucletron Planning System. Patients were grouped into two groups, according to their risk for biochemical failure: low-risk group without (LR) or with neoadjuvant total androgen deprivation (AD) prior to EBRT (LR+AD) and high-risk group without (HR) or with neoadjuvant AD (HR+AD), for bNED and dose-escalation protocol. LR encompassed patients who presented GS<6, T1 or T2a and or initial PSA<10 ng/ml, who were treated with 16 Gy (4 Gy fractions, b.i.d.) HDR-B. The remaining patients were grouped into HR or HR+AD and received 20 Gy (5 Gy fractions, b.i.d.) HDR-B. The planning was optimized using the standard geometric optimization. Biological effective doses (BED) for tumor control and late responding tissue were calculated using a alpha/beta ratio of 1.5 and 3 Gy, respectively. They were matched with bNED, acute and late gastrointestinal (GI) and urological (GU) morbidity, according to the RTOG/EORTC scoring criteria. Median age of patients was 68 years (range 47-83), with a median follow-up of 41 months (range 18-48). The crude and actuarial biochemical controls (bNED) in 48 months for all patients were 69.5 and 75.3%, respectively. When grouped into LR, LR+AD, HR and HR+AD the actuarial bNED were 78.2, 76, 76 and 72.3% (P=0.89), respectively. Acute GU and GI morbidity G1-2 were seen in 18.5% (20/108) and 10.2% (11/108) of patients with spontaneous regression. Late GI and GU morbidity G1-2 were seen in 12% (13/108) and 4.6 (5/108) of patients, with no need of intervention. No acute or late G3-4 GU or GI morbidity was seen. There are many advantages in HDR-B, but the most important ones are the capability of on-line dosimetry, quality control and the procedure being very conformal. There is a low incidence of GU and GI acute and late morbidity with acceptable bNED when treating initial and locally advanced prostate cancer with HDR-B as a boost to EBRT, but we still need to wait for results of phase III open trials that analyze HDR-B and conformal therapy.

Interstitial low-dose-rate brachytherapy as a salvage treatment for recurrent head-and-neck cancers: long-term results

Purpose: Recurrent cancers of the head and neck within previously irradiated volume pose a serious therapeutic challenge. This study evaluates the response and long-term tumor control of recurrent head-and-neck cancers treated with interstitial low-dose-rate brachytherapy.Methods and Materials: Between 1979 and 1997, 220 patients with prior radiation therapy with or without surgery for primary tumors of the head and neck were treated for recurrent disease or new primary tumors located within previously irradiated volumes. A majority of these patients had inoperable diseases with no distant metastasis. There were 136 male and 84 female patients, and median age was 56 years. All patients had previously received radiation therapy as the primary treatment or adjuvant treatment following surgery, with a median dose of 57.17 cGy (range, 39–74 cGy). The salvage brachytherapy consisted of a low-dose-rate, afterloading Iridium192 implant, which delivered a median minimum tumor dose of 53 Gy to a mean tumor volume of 68.75 cm2. Sixty percent of the patients also received interstitial hyperthermia, and 40% received concurrent chemotherapy as a radiosensitizing and potentiating agent.Results: At a minimum 6-month follow-up, local tumor control was achieved in 77% (217/282) of the implanted tumor sites. The 2, 5, and 10-year disease-free actuarial survival rates for the entire group were 60%, 33%, and 22%, respectively. The overall survival rate for the entire group at 5 years was 21.7%. Moderate to severe late complications occurred in 27% of the patients.Conclusion: It has been estimated that approximately 20–30% of head-and-neck cancer patients undergoing definitive radiation therapy have recurrence within the initial treatment volume. Furthermore, similar percentages of patients who survive after successful irradiation develop new primary tumors of the head and neck or experience metastatic neck disease. A majority of such patients cannot be treated with a repeat course of external beam irradiation because of limited normal tissue tolerance, leading to unacceptable morbidity. However, in a select group of these patients, salvage interstitial brachytherapy may play an important role in providing patients with durable palliation and tumor control, as well as a chance for cure.

Intraluminal Brachytherapy for Malignant Endobronchial Tumors: An Update on Low-Dose Rate Versus High-Dose Rate Radiation Therapy

Although the evolution from low-dose rate (LDR) to high-dose rate (HDR) brachytherapy for malignant endobronchial tumors was presumably based on economy, patient convenience, and radiation protection, our experience with both modalities permits assessment of the pros and cons of each technique. In November 1991, our HDR remote afterloading brachytherapy unit became operational. By that time, we had treated 110 patients (group 1) with malignant endobronchial obstruction with LDR brachytherapy. Since then, all patients have been treated with HDR brachytherapy. The outcome of our first 110 patients (group 2) treated with HDR brachytherapy is presented in this communication, using group 1 as the historic control group. In group 1, patients were treated with 1 or 2 sessions of 30-60 Gy, each calculated at a 1-cm radius. In group 2, patients received 3 or 4 weekly treatments of 7 Gy, each calculated at a 1-cm radius. The majority of patients in each group had previously received a full course of external beam irradiation, and a history of laser bronchoscopy was also similar for the 2 groups. Differences in bronchoscopic response rate (82% vs. 96%, respectively) and complications (3.6% vs. 2.7%, respectively) were statistically insignificant between the LDR group and the HDR group. We believe HDR brachytherapy is the state-of-the-art modality in intraluminal therapy for endobronchial malignancies.

Ionizing radiation induces CD20 surface expression on human B cells.

The CD20 surface antigen is expressed on the great majority of B-cell lymphoma cases. The expression of this antigen ranges from moderate to bright, and it is neither internalized nor shed. These characteristics make CD20 a common target for antibody directed lymphoma therapy. The development of strategies to significantly increase CD20 expression on lymphoma cells is therefore of great interest as a means of increasing specific targeting and cell kill in antibody therapy and radio-immunotherapy. We present here data demonstrating that relatively low doses of external beam radiotherapy are capable of significant and consistent increases in CD20 surface expression in vitro. The effect is dose related up to approximately 10 Gy and is maximal in the first day after radiotherapy. We believe that these data may suggest a potent way to combine a short pretreatment course of external beam radiotherapy with a subsequent course of immunotherapy using either an unlabeled antibody or a radio-immunotoxin.

CONSERVATIVE TREATMENT OF RECTAL ADENOCARCINOMA

Endocavitary radiotherapy and transrectal excision are highly effective treatments for properly selected patients with favorable early-stage rectal adenocarcinoma. The likelihood of local control and survival after treatment with either modality is similar, and differences among various series probably reflect selection. The parameter most predictive of local control and survival in the authors' series was tumor configuration. As has been previously observed, "selection is the silent partner of success." Suitable candidates for endocavitary radiotherapy or wide local excision are patients whose tumors are 3 cm or less in diameter, well-to-moderately differentiated, exophytic, mobile, limited to the submucosa on transrectal ultrasound, and within 10 cm of the anal verge. The advantages of endocavitary irradiation are (1) it is an outpatient procedure, (2) it does not require anesthesia, and (3) it is less expensive than transrectal excision. The advantages of transrectal excision are (1) it may be performed during one brief hospitalization (as opposed to four outpatient visits), and (2) a small subset of patients will have pathologic findings predicting an increased risk of regional lymph node involvement, revealing the need to treat the nodes with external-beam radiotherapy. A disadvantage of wide local excision is that some patients who would be suitable for a local procedure alone must be subjected to a course of external-beam radiotherapy when they are found to have equivocal or positive margins. Patients who are treated with transrectal excision and external-beam radiotherapy have less favorable lesions and are not comparable with patients who are treated with endocavitary radiotherapy or wide local excision alone. They are best compared with patients who have undergone major surgery consisting of abdominoperineal resection or low anterior resection. Because the risk of positive nodes is significantly increased with adverse pathologic findings such as poor differentiation, invasion of the muscularis propria, and endothelial-lined space invasion, a subset of these patients treated with wide local excision would have positive nodes. This subset of patients is not comparable with patients with stage pT1N0 and pT2N0 tumors treated with major surgery. The latter group of patients undergo complete surgical staging, whereas the pathologic staging for patients who undergo wide local excision and radiotherapy is limited to the extent of the primary tumor. With this caveat in mind, wide local excision and radiotherapy seem to result in locoregional control and survival rates similar to the rates obtained with major surgery for patients with pT1 and pT2 cancers (Table 5). Patients who should receive postoperative irradiation have tumors that exhibit one or more of the following characteristics: size greater than 3 cm in diameter, poorly differentiated, invasion of the muscularis propria, endothelial-lined space invasion, fragmented resection, equivocal or positive margins, or perineural invasion. Patients with gross residual disease are not suitable candidates for radiotherapy and require further surgery. The authors' policy is to treat these patients with chemoradiation followed by resection. Patients thought to have transmural invasion before treatment are probably best treated with preoperative chemoradiation combined with major surgery, although a subset of patients can be downstaged and rendered suitable for a wide local excision.

Retrospective stratification of a consecutive cohort of prostate cancer patients treated with a combined regimen of external-beam radiotherapy and brachytherapy

Purpose: The evaluation of clinical variables that influence biochemical relapse-free survival in a cohort of patients treated by combined radiotherapy over a fixed interval. Methods and Materials: Three hundred forty-eight patients diagnosed with clinical Stage T1–T3a prostate cancer were treated with a course of 103Pd or 125I brachytherapy followed by a limited course of external beam radiation formed the basis for study. All censored patients had a minimum 2-year follow-up. Biochemical relapse-free survival (BRFS) was estimated using a modified American Society for Therapeutic Radiology and Oncology consensus definition. Discrete “risk groups” were developed based on BRFS as influenced by pretreatment parameters. Results: Significant risk factors contributing to biochemical failure were serum prostate-specific antigen (PSA) greater than 20 ng/mL, Gleason sum of 7 or greater, or clinical stage T2c or greater. Five-year biochemical control for those exhibiting no risk factor was 88%; one risk factor, 75%; two or more risk factors, 51%. The differences in BRFS among all three risk groups were statistically significant. Outcomes for patients presenting with PSA 10 to 20 ng/mL, but otherwise low-risk disease, fared no differently from those low risk patients presenting with PSA less than 10 ng/mL. Conclusions: Combined radiotherapy with 103Pd or 125I followed by external beam radiotherapy achieves a high rate of biochemical and clinical control in patients with low- to intermediate-risk clinically organ confined disease.

57 The role of brachytherapy in the treatment of breast cancer: The American Brachytherapy Society Recommendations

Whole-breast external-beam radiation therapy (EBRT) involves a 6-week course of fractionated treatments. In contrast, brachytherapy can be completed in a 4- to 5-day treatment course. Because of this shortened time frame, there has been interest in breast brachytherapy as a sole modality after lumpectomy. The American Brachytherapy Society (ABS) has issued guidelines specifically for the use of brachytherapy in breast carcinoma. In these guidelines, the ABS addresses important areas of controversy related to the indications, execution, and evaluation of breast implants when utilized in the following settings: as the sole treatment modality following lumpectomy, as an alternative to a 6-week course of EBRT following lumpectomy, as a boost following whole-breast irradiation, and for the treatment of local recurrences following breast-conservation treatment. The ABS recommends a precise definition and meticulous delineation of the clinical target volume. In addition, the Society recommends the routine use of dose-volume histograms and a dose-homogeneity index as tools to ensure reproducible brachytherapy and to allow interinstitutional comparisons. Brachytherapy as a sole modality is currently considered investigational and should be performed in the context of a controlled clinical trial. Practitioners and cooperative groups are encouraged to use these guidelines to formulate treatment and dose-reporting policies, but responsibility for medical decisions ultimately rests with the treating radiation oncologist.

Carcinoma of the external auditory canal and middle ear

Purpose: To evaluate therapeutic modalities used at our institutions regarding local control, disease-free survival and actuarial survival in carcinoma of the external auditory canal and middle ear, in an attempt to provide guidelines for therapy. Methods and Materials: A series of 27 patients with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions were analyzed with particular reference to tumor size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques employed. Clinical endpoints were freedom from local failure, overall survival, and disease-free survival. The median follow-up was 2.7 years (range 0.1–17.9 years). Results: Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 61%. According to the Pittsburgh classification, the actuarial 5-year survival rate for early disease (T1 and T2 tumors) was 86%, for T3 tumors 50%, and T4 stages 41%. Patients with tumors limited to the external auditory canal had a 5-year survival rate of 100%, patients with tumor invasion of the temporal bone 63%, and patients with tumor infiltration beyond the temporal bone 38%. The rate of freedom from local recurrence was 50% at 5 years. Unresectability by dural and cerebral infiltration, and treatment factors such as complete resection or resection with tumor beyond surgical margins are of prognostic relevance. All patients with dural invasion died within 2.2 years. The actuarial 5-year survival rate of patients with complete tumor resection was 100%, but 66% in patients with tumor beyond surgical margins. 192Iridium high-dose-rate (HDR) afterloading brachytherapy based on three-dimensional computed tomography (3D CT)-treatment planning was an effective tool in management of local recurrences following surgery and a full course of external beam radiotherapy. Conclusion: Surgical resection followed by radiotherapy adapted to stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

Anesthesia for pediatric external beam radiation therapy

Background: For very young patients, anesthesia is often required for radiotherapy. This results in multiple exposures to anesthetic agents over a short period of time. We report a consecutive series of children anesthetized for external beam radiation therapy (EBRT).Methods: Five hundred twelve children ≤ 16 years old received EBRT from January 1983 to February 1996. Patient demographics, diagnosis, anesthesia techniques, monitoring, airway management, complications, and outcome were recorded for the patients requiring anesthesia.Results: One hundred twenty-three of the 512 children (24%) required 141 courses of EBRT with anesthesia. Anesthetized patients ranged in age from 20 days to 11 years (mean 2.6 ± 1.8 ). The frequency of a child receiving EBRT and requiring anesthesia by age cohort was: ≤ 1 year (96%), 1–2 years (93%), 2–3 years (80%), 3–4 years (51%), 4–5 years (36%), 5–6 years (13%), 6–7 years (11%), and 7–16 years (0.7%). Diagnoses included: primary CNS tumor (28%), retinoblastoma (27%), neuroblastoma (20%), acute leukemia (9%), rhabdomyosarcoma (6%), and Wilms’ tumor (4%). Sixty-three percent of the patients had been exposed to chemotherapy prior to EBRT. The mean number of anesthesia sessions per patient was 22 ± 16. Seventy-eight percent of the treatment courses were once daily and 22% were twice daily. Anesthesia techniques included: short-acting barbiturate induction + inhalation maintenance (21%), inhalation only (20%), ketamine (19%), propofol only (12%), propofol induction + inhalation maintenance (7%), ketamine induction + inhalation maintenance (6%), ketamine or short-acting barbiturate induction + inhalation maintenance (6%). Monitoring techniques included: EKG (95%), O2 saturation (93%), fraction of inspired O2 (57%), and end-tidal CO2 (55%). Sixty-four percent of patients had central venous access. Eleven of the 74 children with a central line developed sepsis (15%): 6 of the 11 were anesthetized with propofol (55%), 4 with a short-acting barbiturate induction plus inhalation maintenance (36%), and 1 with inhalation alone (9%). Eight of the 11 (73%) received prior chemotherapy.Conclusion: Anesthesia was generally necessary at ≤ 3 years, and rarely required at > 5 years of age. Sepsis associated with frequent use of the central venous access line was seen in 15% of the patients with these lines.

ANESTHESIA AND PEDIATRIC EXTERNAL BEAM RADIATION THERAPY-A REVIEW OF 512 PATIENTS

S296 INTRODUCTION: The use of general anesthesia to produce immobility and to reduce emotional stress in pediatric patients undergoing external beam radiation therapy (EBRT) has been gaining in popularity over the past decade. We review our experience with a large series of pediatric patients undergoing multiple anesthetics for EBRT. METHODS: 512 children <or=to 16 yrs old received EBRT at Duke from 1/83 to 2/96. The charts of children anesthetized for EBRT during this period were reviewed. Patient demographics, diagnosis, anesthesia techniques, and complications were recorded. RESULTS: Of the 512 children, 123 (24%) required anesthesia for 141 courses of EBRT. These patients ranged in age from 20 days to 11 years, and consisted of 71 males (58%) and 52 females (42%). Among the patients were 95 Caucasians (77%), 26 African-Americans (21%), and 2 Native Americans (2%). Children under three were the most likely to require anesthesia for EBRT - 90% vs 28% of children from 3-7 yrs of age vs 0.7% over age 7. The most common diagnoses were: primary CNS tumor (28%), retinoblastoma (26%), and neuroblastoma (18%). The mean number of treatments per child was 22 +/- 16 with a median of 24, and a range of 1 to 65. 78% of the treatments were Q.D. and 22% were B.I.D. Treatment position was supine for 114 courses (81%), prone for 23 (16%), and combined for 4 (3%). In 88 of the courses (62%), the child had a prior or simultaneous exposure to cytotoxic/immunosuppressive chemotherapy. The most commonly used chemotherapeutic agents were vincristine, cyclophosphamide, VP16, cisplatin, adriamycin, and prednisone or dexamethasone. Anesthesia techniques consisted of ketamine alone (19%), propofol infusion (12%), halogenated inhalation agent alone (20%), intravenous induction (ketamine, barbiturate, or propofol) + halogenated inhalation maintenance (43%), midazolam alone (2%), and other (4%). The airway was maintained with either a standard mask (82%), a laryngeal mask (4%), or with intubation (14%). Intubation was typically used only at the time of radiation simulation. Complications included laryngeal spasm or airway obstruction occurring at least once during a course of EBRT (13%), and infected central venous line (occurring in 11 of the 74 children with a central line for an incidence of 15%). In ten of the children with CVP line sepsis, the line had been accessed for anesthesia use, utilizing propofol in 6 patients and barbiturate in 4. No child experienced signs or symptoms of aspiration, or clinically detectable hepatic dysfunction. CONCLUSIONS: Over a 13 yr period 123 children were anesthetized multiple times over a short time period for EBRT. Satisfactory conditions for EBRT were achieved with a variety of anesthetic techniques. The incidence of adverse events was low. Mask or laryngeal mask airway was adequate in the vast majority of patients. Despite the multiple exposures to anesthetic agents, including halogenated anesthetics, and hepatotoxic chemotherapeutic agents, no child developed hepatic dysfunction severe enough to be clinically detectable. The most common complications were airway obstruction and CVP line sepsis. The incidence of CVP line sepsis appears to be unrelated to to the anesthetic agent used and emphasizes the need to follow strict sterile protocols in accessing these lines. (Table 1)Table 1: Types of Anesthesia Used in 141 Courses of Pediatric EBRT

Contemporary brachytherapy approaches in non–small-cell lung cancer

Brachytherapy has the ability to deliver a higher tumor dose compared to external beam irradiation, while sparing normal tissue outside the tumor; it is the most effective means of delivering conformal radiation and can be tailored to clinical circumstances, either at open surgery or in an ambulatory setting, which is currently the preferred method. Intraoperative lung and/or endobronchial brachytherapy in the management of non-small-cell lung cancer offers a good curative potential in patients with accessible localized tumors, well defined and small to moderate in size, that have not metastasized to the lymph nodes and are technically or medically inoperable. Effective palliation can be frequently obtained by endobronchial brachytherapy on an outpatient procedure basis. Brachytherapy administered simultaneously with chemotherapy is better tolerated than a course of external beam irradiation and chemotherapy.

Target position variability throughout prostate radiotherapy

Purpose: To quantify the variability in prostate and seminal vesicle position during a course of external beam radiotherapy, and to measure the proportion of target variability due to setup error.Methods and Materials: Forty-four weekly planning computerized tomography (CT) studies were obtained on six patients undergoing radiotherapy for prostate cancer. All patients were scanned in the radiotherapy treatment position, supine with an empty bladder, with no immobilization device. All organs were outlined on 3-mm-thick axial CT images. Anterior and lateral beam’s eye view digitally reconstructed radiographs and multiplanar reformatted images were generated. The position of the prostate and seminal vesicles relative to the isocenter location as set that day was recorded for each CT study. Target position relative to a bony landmark was measured to determine the relative contribution of setup error to the target position variability.Results: The seminal vesicle and prostate position variability was most significant in the anterior–posterior (AP) direction, followed by cranial–caudal (CC) and mediolateral (ML) directions. Setup error contributed significantly to the total target position variability. Rectal filling was associated with a trend to anterior movement of the prostate, whereas bladder filling was not associated with any trends. Although most deviations from the target position determined at the initial planning CT scan were within 10 mm, deviations as large as 15 mm and 19 mm were seen in the prostate and seminal vesicles respectively. Target position variations were evenly distributed around the initial target position for some patient studies, but unpredictable patterns were also seen. From a simulation based on the observed variability in target position, the AP, CC, and ML planning target volume (PTV) borders around the clinical target volume (CTV) required for target coverage with 95% certainty are 12.4 mm, 10.3 mm, and 5.6 mm respectively for the prostate and 13.8 mm, 8.6 mm, and 3.9 mm respectively for the seminal vesicles.Conclusion: Target position variability is significant during prostate radiotherapy, requiring large PTV borders around the CTV. This target position variability may be potentially reduced by improving the setup accuracy.

Contemporary brachytherapy approaches in non–small‐cell lung cancer

Brachytherapy has the ability to deliver a higher tumor dose compared to external beam irradiation, while sparing normal tissue outside the tumor; it is the most effective means of delivering conformal radiation and can be tailored to clinical circumstances, either at open surgery or in an ambulatory setting, which is currently the preferred method. Intraoperative lung and/or endobronchial brachytherapy in the management of non–small-cell lung cancer offers a good curative potential in patients with accessible localized tumors, well defined and small to moderate in size, that have not metastasized to the lymph nodes and are technically or medically inoperable. Effective palliation can be frequently obtained by endobronchial brachytherapy on an outpatient procedure basis. Brachytherapy administered simultaneously with chemotherapy is better tolerated than a course of external beam irradiation and chemotherapy. J. Surg. Oncol. 1998;69:258–264. © 1998 Wiley-Liss, Inc.

Conservative treatment of anorectal tumors

Our purpose was to evaluate the results of interstitial radiotherapy of anorectal tumors. From 1972 to 1993, one of the authors treated 45 patients by an interstitial implant for anorectal tumors. Of these, 33 patients suffered from primary tumors, 19 from squamous carcinoma, 2 from basaloid carcinoma of the anus and the other 12 from primary adenocarcinoma of the rectum. Of 12 patients treated for local recurrence, 10 had adenocarcinoma and 2 squamous cell carcinoma. Of the 33 patients with primary tumors, 27 received a course of external-beam radiotherapy before the implant. The median follow-up was 35 months.

The relationship between biochemical failure and time to nadir in patients treated with external beam therapy for T1-T3 prostate carcinoma

Purpose and background: To determine a prostatic-specific antigen (PSA) nadir value and time to nadir that predict a high probability of freedom from biochemical failure in men treated with external beam therapy for prostate cancer. Materials and methods: Between January 1990 and March 1994, 228 men with T1-T3 adenocarcinoma of the prostate received a radical course of external beam irradiation with no prior or adjuvant hormonal therapy. All men had pre- and post-treatment serum PSA evaluations, and were followed up for at least 24 months, to ensure PSA nadir was reached. Biochemical failure was defined as three successive post-treatment rises in serum PSA, regardless of the magnitude of elevation. Results: Overall, 4-year biochemical disease-free survival (BDFS) was 42%. PSA nadir was predictive of subsequent BDFS. For those whose serum PSA nadir was ≤1 ng/ml, 4-year BDFS was 70%, versus 12% for those with serum PSA nadir >1 ng/ml ( P=<0.001). The 4-year BDFS for patients with time to nadir ≤1 year, was 28%, versus 58% for those with time to nadir >1 year ( P<0.001). For patients with PSA nadir ≤1 ng/ml, 4-year BDFS was 75% for those with time to nadir >1 year, versus 61% for those with time to nadir ≤1 year ( P<0.021). In multivariate analysis, PSA nadir (≤1 ng/ml versus >1 ng/ml, and time to nadir (≤1 year versus >1 year) were independent predictors of BDFS alone with pre-treatment PSA and Gleason score. Conclusion: Only those who achieved PSA nadir ≤1 ng/ml following external beam therapy have a favourable chance of lasting biochemical disease control, while those with nadir >1 ng/ml have a high subsequent failure rate. The prognosis is better in patients with late time to nadir. In addition to PSA nadir, time to nadir, pretreatment PSA, and Gleason score were of independent prognostic significance.

Is prostate specific antigen density an important prognostic indicator for patients with prostate cancer treated with external beam therapy?

The purpose of this study was to determine if prostate specific antigen density (PSAD) is a predictor of outcome following external beam radiotherapy for prostate cancer, and to compare it with other prognostic factors. Between January 1990 and December 1993, 205 patients with T1-T3 adenocarcinoma of the prostate received a radical course of external beam irradiation, with no prior or adjuvant hormonal therapy. All patients had pre- and post-treatment serum prostate specific antigen (PSA) evaluation. They were followed up for at least 24 months. PSAD was defined as the ratio of pre-treatment serum PSA to the prostate volume, as determined from CT treatment planning scans. Prostate volumes were calculated using the prostate ellipse formula. Median PSA density was 0.37, with a range 0.01-6.7. Biochemical failure was defined as three consecutive rises in serum PSA, regardless of the magnitude of elevation. 4-year biochemical disease-free survival (BDFS) for patients with PSAD < or = 0.3 was 60%, compared with 22% for patients with PSAD > 0.3 (p = < 0.001). In a multivariate analysis, pre-treatment PSA (p = < 0.001), Gleason score (p = 0.002), and stage (p = 0.03) were independent predictors of BDFS, while PSAD was not an important prognosticator (p = 0.62). Pre-treatment serum PSA is the most important prognosticator of BDFS, following external beam radiotherapy, for patients with prostate cancer. PSA density did not predict treatment outcome.

Conservative treatment of anorectal tumors.

To evaluate the results of interstitial radiotherapy of anorectal tumors. From 1972 to 1993, one of the authors treated 45 patients by an interstitial implant for anorectal tumors. Of these, 33 patients suffered from primary tumors, 19 from squamous carcinoma, 2 from basaloid carcinoma of the anus and the other 12 from primary adenocarcinoma of the rectum. Of 12 patients treated for local recurrence, 10 had adenocarcinoma and 2 squamous cell carcinoma. Of the 33 patients with primary tumors, 27 received a course of external-beam radiotherapy before the implant. The median follow-up was 35 months. Local response depended on the tumor volume treated. All 21 anal tumors showed complete response, 5 patients developed local recurrence and 4 distant metastases: 3 died from their disease. Of 12 rectal adenocarcinomas, 9 responded completely, 4 patients developed local recurrence and 4 distant metastases; 6 died from active disease. In the last group of 12 patients who were treated for recurrent tumors, 7 responded completely. One patient developed local recurrence and 9 distant metastases, only 4 are alive. A combination of external-beam and interstitial radiotherapy is a relatively simple, non-mutilating, but well-tolerated and very effective method of treatment for early carcinoma of the lower rectum and anus.

Craniopharyngioma: Improving outcome by early recognition and treatment of acute complications

Purpose : To assess the frequency, mode of presentation, treatment, and outcome of acute complications in patients with craniopharyngioma around the time of radiotherapy. Methods and Materials : A review was made of 188 patients with craniopharyngioma treated with conservative surgery and external beam radiotherapy at the Royal Marsden Hospital between 1950 and 1992. Results : Twenty six (14%)(95% confidence interval: 9–19%) patients with craniopharyngioma developed acute deterioration immediately before, during and 2 months after radiotherapy with visual deterioration (19 patients), hydrocephalus (7 patients), and global deficit (7 patients). Cystic enlargement with or without hydrocephalus was the most common cause of deterioration. No patient or disease characteristics were predictive of deterioration on univariate or multivariate analysis. Eighteen patients had surgical intervention at the time of deterioration and survived the immediate period. Six of seven patients who did not have surgical intervention died. All patients who survived the postcomplication period completed the full course of external beam radiotherapy. The 10-year progression-free survival of 162 patients without deterioration was 86%, and of 18 patients with acute deterioration who recovered after surgery, 77%. Conclusion : Patients with craniopharyngioma develop acute deterioration around the time of radiotherapy owing to cystic enlargement and/or hydrocephalus which does not represent tumor progression. Early recognition and appropriate surgical treatment followed by conventional full-dose radiotherapy are associated with good longterm outcome.