Ted N. Roman

The prediction of late rectal complications in patients treated with high dose-rate brachytherapy for carcinoma of the cervix

PURPOSE The aim of this work is to investigate an unusually high rate of late rectal complications in a group of 43 patients treated with concomitant irradiation and chemotherapy for carcinoma of the cervix between December 1988 and April 1991, with a view to identifying predictive factors. METHODS AND MATERIALS The biologically effective dose received by each patient to the rectal reference point defined by the International Commission of Radiation Units and Measurements, Report 38, were calculated. Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose-rate intracavitary treatments of 10 Gy each prescribed to point A. Cisplatin 30 mg/m2 was given weekly throughout the duration of the irradiation. The results have been compared to data from 119 patients treated with irradiation alone to assess the confounding effect of the cisplatin. RESULTS The relationship between the biologically effective dose delivered to the rectal reference point and the development of late complications shows a strong dose-response with a threshold for complications occurring at approximately 125 Gy3 corresponding to a brachytherapy dose of approximately 8 Gy per fraction. This value is approximately the same biologically effective dose threshold as that found for external beam irradiation in the head and neck region. The data from the group of patients treated without cisplatin is comparable to the data from the first group of patients in the lower dose ranges; the higher doses were not used and thus are not available for comparison. CONCLUSION Using the linear quadratic model applied to our clinical results, we have established a threshold for late rectal complications for patients treated with external beam irradiation and high dose-rate brachytherapy for carcinoma of the cervix. This threshold is consistent with similar data for external beam irradiation in the head and neck region.

Weekly cisplatin plus external beam radiotherapy and high dose rate brachytherapy in patients with locally advanced carcinoma of the cervix.

PURPOSE Prospective, single arm, Phase I/II trial performed to assess the efficacy and toxicity of the concomitant use of weekly cisplatin and pelvic radiotherapy in patients with locally advanced carcinoma of the cervix. METHODS AND MATERIALS Between December 1988 and April 1991, 50 previously untreated patients with bulky, locally advanced, squamous cell carcinoma entered the study. All patients were evaluated by a gynecologist and a radiation oncologist and were submitted to standard pre-treatment staging procedures. The International Federation of Gynecology and Obstetrics stage distribution was as follows: IIA three patients, IIB seventeen, IIIA two, IIIB 25, and IVA three. Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose rate intracavitary treatments given on a weekly basis to a total dose of 30 Gy to point A. Cisplatin 30 mg/m2 was also given weekly starting on day 1 of radiotherapy. RESULTS With a median follow-up time of 27 months, complete response was seen in 88% (44/50) of the patients. The actuarial survival rate at 44 months was 65%. Total pelvic failure rate was 26% (13/50). Of the 44 patients who achieved a complete remission, only seven have failed in the pelvis. Distant disease was observed in 24% of the cases. Treatments were well tolerated with no patient requiring an interruption in the radiotherapy. However, the incidence of late gastrointestinal toxicity was high, with 10 patients developing a rectal ulcer (four colostomies for severe bleeding), two patients a small bowel obstruction, and two patients a recto-vaginal fistula. Moreover, gastrointestinal complications appeared sooner than expected, at a median follow-up time of 11 months after completion of treatment. CONCLUSION The combination of weekly cisplatin and radiotherapy appears to be a very effective regimen for patients with locally advanced carcinoma of the cervix, but resulted in a relatively high frequency of late gastrointestinal complications.

Rectal complications in patients with carcinoma of the cervix treated with concomitant cisplatin and external beam irradiation with high dose rate brachytherapy: A dosimetric analysis

PURPOSE This paper reports a dosimetric study of 43 patients treated with a combination of concomitant radiotherapy and chemotherapy (cisplatin) for locally advanced carcinoma of the cervix with the aim of investigating the correlation between the radiation dose to the rectum and the incidence of late rectal complications. METHODS AND MATERIALS Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose rate intracavitary treatments given weekly, concurrent with the last 3 weeks of external beam therapy, to a total dose of 30 Gy to point A. Cisplatin 30 mg/m2 was given weekly throughout the duration of the external beam irradiation. The brachytherapy irradiated volume was reconstructed from the orthogonal treatment radiographs to accurately locate the reference points defined by the International Commission of Radiation Units and Measurements (ICRU), report 38. The doses calculated at these points were compared to in vivo dose measurements performed immediately prior to treatment. RESULTS The group of patients who were calculated to have received a dose to the rectal reference point greater than the prescribed point A dose (9/13) had a significantly greater probability of development of late rectal complications compared to the group of patients who were calculated to have received less than the prescribed point A dose at this rectal point (7/30), p = 0.003. There was no correlation of rate of complication with the in vivo measured dose in the rectum, stage of disease, or age. At 40 months post treatment, the group of patients receiving the higher dose to the rectal reference point had an actuarial rate of serious (Grade 3 and 4) rectal complications of 46% compared to a rate of 14% in the remainder. In terms of survival, the group of patients receiving the higher dose to the rectal reference point have all survived, whereas the group of patients receiving the lower dose to the rectal reference point have a significantly different rate of survival of 72%, p = 0.046. CONCLUSION This investigation has revealed a significant correlation between the dose calculated at the rectal point defined by the ICRU and the incidence of late rectal complications in patients with carcinoma of the cervix undergoing concomitant radiotherapy and chemotherapy. Thus, this rectal reference point appears to be a useful prognostic indicator of late rectal complications in these patients and we recommend that the brachytherapy dose delivered to this rectal point be limited to the dose prescribed to point A for treatment regimens using three fractions of 8-10 Gy each, limiting the total dose to this point, including the external beam component, to 76 Gy. Further study will be required to determine whether this rule should be applied to patients receiving irradiation alone.

High dose rate afterloading intracavitary therapy in carcinoma of the cervix

From January 1984 through December 1986, 87 patients with previously untreated carcinoma of the cervix received external beam pelvic irradiation and high dose rate intracavitary therapy (HDRT). There were 18 Stage IIA patients, 39 Stage IIB, and 30 Stage IIIB. The median age was 60 years and the median follow-up time was 42 months for patients at risk. Radiotherapy consisted of external megavoltage irradiation to the whole pelvis (median dose 4600 cGy) combined with one (6 patients), two (51 patients), or three (30 patients) HDRT insertions. A high dose rate remote afterloading unit with 60Co sources was used to deliver the HDRT. The prescribed dose to point A was between 800 and 1000 cGy per treatment. The dose rate at point A initially was approximately 150 cGy/min and dropped to approximately 100 cGy/min during the duration of the study. Treatments with multiple fractions were given at weekly intervals. The overall actuarial survival at 5 years was 88% for Stage IIA, 64% for Stage IIB and 32% for Stage IIIB patients. Pelvic recurrence remained the major cause of failure. Grade III and IV late complications included proctitis and bowel obstruction in six patients each. We conclude that HDRT results are similar to those obtained with conventional low dose rate intracavitary systems. HDRT is cost effective and minimizes exposure to personnel. Several questions, such as the total number of insertions required, dose per HDRT insertion, and optimal HDRT insertion schedule remain unanswered and further experience is needed to better clarify these issues.

Surface applicators for high dose rate brachytherapy in aids-related Kaposi's sarcoma

PURPOSE The development of commercially available surface applicators using high dose rate remote afterloading devices has enabled radiotherapy centers to treat selected superficial lesions using a remote afterloading brachytherapy unit. The dosimetric parameters of these applicators, the clinical implementation of this technique, and a review of the initial patient treatment regimes are presented. METHODS AND MATERIALS A set of six fixed-diameter (1, 2, and 3 cm), tungsten/steel surface applicators is available for use with a single stepping-source (Ir-192, 370 GBq) high dose rate afterloader. The source can be positioned either in a parallel or perpendicular orientation to the treatment plane at the center of a conical aperture that sits at an SSD of approximately 15 mm and is used with a 1-mm thick removable plastic cap. The surface dose rates, percent depth dose, and off-axis ratios were measured. A custom-built, ceiling-mounted immobilization device secures the applicator on the surface of the patients lesion during treatment. RESULTS Between November 1994, and September 1996, 16 AIDS-related Kaposis sarcoma patients having a total of 120 lesions have been treated with palliative intent. Treatment sites were distributed between the head and neck, extremity, and torso. Doses ranged from 8 to 20 Gy, with a median dose of 10 Gy delivered in a single fraction. Treatments were well tolerated with minimal skin reaction, except for patients with lesions treated to 20 Gy who developed moderate/severe desquamation. CONCLUSION Radiotherapy centers equipped with a high dose rate remote afterloading unit may treat small selected surface lesions with commercially available surface applicators. These surface applicators must be used with a protective cap to eliminate electron contamination. The optimal surface dose appears to be either 10 or 15 Gy depending upon the height of the lesion.

Treatment results of high dose rate brachytherapy in patients with carcinoma of the cervix.

PURPOSE The combination of external beam irradiation and low-dose-rate brachytherapy is known to be an effective form of treatment in carcinoma of the cervix and any change from this well-established therapeutic combination must be able to equal or improve the treatment results. Since 1984 we have been using high dose rate brachytherapy in conjunction with external beam irradiation for patients with carcinoma of the cervix. This paper reports our long term treatment results in terms of local disease control, survival, and complications. METHODS AND MATERIALS Between January 1984 and December 1989, 187 previously untreated patients with carcinoma of the cervix underwent combined external beam irradiation and high dose rate brachytherapy. The International Federation of Gynecology and Obstetrics stage distribution of patients was as follows: I B = 15, II A = 35, II B = 68, III A = 9, III B = 54, IV A = 6. External beam irradiation to the whole pelvis was delivered by megavoltage irradiation with once-a-day fractionation, to a median dose of 4600 cGy. High dose rate brachytherapy was delivered by a high-dose-rate remote controlled afterloading unit, containing 20 spherical Cobalt 60 sources with a nominal activity of 19 GBq (0.5 Ci) at the time of installation, giving a typical dose rate to point A of 160 cGy/min, decreasing to about 80 cGy/min at the end of the 5-year study. One to 3 high dose rate brachytherapy treatments delivering 800 to 1000 cGy to point A were given weekly concurrently with the last 2 to 3 weeks of radiation therapy, or following its completion. Maximum rectal and bladder doses were routinely measured for each treatment. RESULTS Overall 5-year actuarial survivals were as follows: I B = 72%, II A = 65%, II B = 66%, III A = 66%, III B = 45%. Five-year actuarial pelvic control rates were as follows: I B = 66%, II A = 83%, II B = 78%, III A = 88%, III B = 40%. At a median follow-up time of 54 months for patients at risk, 23 patients developed 25 complications attributable to radiotherapy (13 rectal, 3 bladder, 8 small bowel, 1 fistula) at a median time of 18 months following completion of treatment. Thirteen complications (7.6%) were grades 3 or 4. Patients with Stage II disease had a higher incidence of complications than patients with Stages I and III disease (p < 0.05). Rectal complications were significantly higher in patients who received a total rectal dose > 5400 cGy (p = 0.045). CONCLUSION High-dose-rate brachytherapy treatment results are comparable to those obtained with low dose rate brachytherapy techniques. The use of three high dose rate brachytherapy insertions is a practical, economical, and safe treatment for patients with carcinoma of the cervix.

Para-aortic irradiation only appears to be adequate treatment for patients with stage I seminoma of the testis

PURPOSE Results of treatment of patients with Stage I seminoma with orchiectomy and radiotherapy are excellent. Even without adjuvant radiotherapy, the relapse rate is only 15-20%; most of the patients fail in the retroperitoneum, with rare failures observed in the pelvis (0.5-2%). In 1991, we began a prospective study evaluating para-aortic lymph node radiation as the only adjuvant treatment for such patients. This paper reports our preliminary results. MATERIALS & METHODS Between March 1991 and January 1996, 35 patients with histologically proven Stage I seminoma were entered in the study. Median age was 37.9 years (range: 27-65 years). A radical inguinal orchiectomy was performed in all patients. Staging workup consisted of a chest X-ray; B-HCG, alpha-fetoprotein, and CT scan of the abdomen and pelvis in all patients. Lymphangiogram was done in 23 (66%) of 35 patients for further evaluation of the retroperitoneal lymph nodes. Radiotherapy consisted of treatment to the para-aortic region only. Parallel opposed fields extending from the top of T11 to the bottom of L5 were used. The median field size was 8.7 x 21.8 cm (range: 7-11 x 18-26 cm). The median total dose, prescribed at midpoint, was 25 Gy given in 15 daily fractions of 1.66 Gy. Follow-up was performed every 3 months for the first year, every 4-5 months for the second and third years, and every 6 months thereafter. Chest X-ray, tumor markers, and CT scan of the pelvis were performed routinely as part of the follow-up investigation. RESULTS At a median follow-up of 39.7 months (range: 16-74 months), 34 (97.1%) of 35 patients are alive with no evidence of disease for an overall actuarial survival rate of 97.1% at 5 years and a cause-specific actuarial survival rate of 100%. Treatment morbidity was limited to Grade I-II acute side effects in 18 (51.4%) of 35 patients. No late side effects were seen. CONCLUSION From our preliminary results, adjuvant radiation treatment limited to the para-aortic lymph node region, without ipsilateral pelvic irradiation, appears to be adequate treatment for Stage I seminoma. Such an approach in our patients resulted in minimal toxicity and excellent disease-free survival.

Radiation therapy of testicular seminoma: a 15-year survey.

A retrospective review of 69 patients with testicular seminoma, stage I and II, treated by orchiectomy and adjuvant irradiation at McGill University Hospitals from 1972 to 1987 was performed. All patients underwent either lymphangiogram or computed axial tomography scan for evaluation of retroperitoneal disease. There were 52 stage I (75%), 13 stage IIA (11%), 2 stage IIB (3%), and 2 stage IIC (Royal Marsden Hospital staging criteria). Median follow-up time was 6.2 years. The 10-year actuarial survivals were 94% and 93% for stages I and II, respectively. Only two stage I patients failed treatment, and both died from metastatic disease. Interestingly, both developed biopsy-proven metastatic brain disease and had no evidence of intra-abdominal recurrence. In stage II disease, only one patient failed the treatment. There was no serious acute toxicity and no late complications have been encountered. Radiation therapy following orchiectomy is the treatment of choice for stage I and for most stage II patients with testicular seminoma. The controversial aspects of radiographie retroperitoneal staging, the use of prophylactic mediastinal irradiation for stage II patients, and the role of surveillance only for stage I patients are discussed.

Is post-operative intracavitary therapy a necessary component of treatment for carcinoma of the endometrium ?

The role of intracavitary therapy in combination with external pelvic radiotherapy for endometrial carcinoma remains controversial. To determine the pelvic failure rate in patients receiving only external pelvic radiotherapy following total abdominal hysterectomy and bilateral salpingo-oophorec-tomy (TAHBSO) for carcinoma of the endometrium, we undertook a retrospective review of all patients referred to the Radiation Oncology Department from January 1977 through December 1984. Patients with grade I, superficially invading tumors were excluded from this analysis. 52 patients were eligible for the study. Three patients who were lost to follow-up immediately after completion of external beam irradiation were excluded, leaving a total of 49 evaluable patients. The median follow-up time is 61 months. Pelvic failure was seen in only 2 patients (4%), both of them occurring concurrent with distant disease. No vaginal vault failures were observed. Overall actuarial survival at 5 years was 82%. We conclude that external beam pelvic radiotherapy alone without intracavitary boost appears to be an adequate treatment for patients undergoing TAHBSO for carcinoma of the endometrium.