Does pelvic lymph nodes irradiation using intensity modulated radiation therapy increase rectal and bladder toxicities in patients with prostate carcinoma?

PURPOSE: this study compared the radiation-related rectal (R) and bladder (B) toxicities in prostate carcinoma patients receiving additional pelvic lymph nodes (PLN) irradiation with those receiving prostate (P) and seminal vesicle (SV) irradiation only. METHODS: thirty-three patients treated with intensity modulated radiation therapy (IMRT) were included. RT doses ranged between 60- 66.6 Gy to SV, 74-77.7 Gy to P and 50.4- 60 Gy to PLN. Max acute R toxicity was graded by a physician according to the RTOG side effect criteria during the period from the initiation of therapy until the end of the third month. Max late R and B toxicities were graded 3 months after the completion of RT by a physician using the RTOG GI and urogenital toxicity score and by patients using EORTC QLQ - PR25 self questionnaire separately. The effects of R and B doses and additional PLN irradiation on acute and late R and B toxicities and compatibility of patient- and physician-graded toxicity scores were investigated. RTOG GI and urogenital toxicity scores and EORTC QLQ - PR25 self questionnaire results were correlated. RESULTS: significant factors for acute R toxicity were: max R; R volume receiving ≥ 68 Gy; and PLN irradiation. PLN irradiation was marginally significant for late R toxicity; the mean B dose was a significant factor for late B toxicity. CONCLUSION: the results of this study suggest that although PLN irradiation increased acute R toxicity, it has no effect on late R and B toxicity. Patient- and physician-evaluated late R and B toxicity scores were concordant.

Dosimetric comparison of ring and ovoid applicators.

PURPOSE: To compare the dosimetry of different vaginal applicators used in the postoperative vaginal cuff irradiation. MATERIALS AND METHODS: In this model dosimetric study, standard ovoid applicator sets with 3 cap sizes (small/15 mm, medium/20 mm, and large/25 mm), and ring applicator sets with 3 diameter sizes (small/26 mm, medium/30 mm, large/34 mm) each with 3 different angles (30, 45, and 60 degrees) were used. Calculations were performed in Plato TPS (Treatment Planning System) as dwell positions of 2.5 mm step and equal dwell time for the sources. For ovoid applicators, the source positions 1-5 were loaded as active on each catheter, and in ring applicators the source positions 1-12, and 18-29; 1-14, and 19-32; 1-17, and 22-37 were loaded for small, medium and large ones, respectively. In addition to ICRU rectum reference point (R(1)), 4 different rectum reference points (RP(s)) (R(2)-R(5)) were defined 1 cm apart. The vaginal cuff RP (V(c)) was defined at 5 mm depth from the vaginal surface. The reference volume dose distribution was obtained according to the V(c) (100%) reference point. The width (w), max-min length (h, h'), and max-min thickness (t, t') of the reference isodoses were measured and max-min reference volume (v, v') was calculated. RESULTS: R(1) dose was higher for ovoids (43.1%) than ring (28.6%), in all applicators. The increase of R(1) dose was parallel to the increase of ovoid/ring size (70-89%). As the applicator (ovoid-ring) size increased, max thickness of the reference isodose also increased (19-50%). For the largest size, the max increase was 62% (74.1-119.88 cm(3)) and 93% (59.15-114.24 cm(3)) for v and v', respectively. However, the magnitude of the reference volume was independent of the ring angle. CONCLUSION: In the present study it was found that when ring applicators were used according to recommended dwell positions, max rectum reference dose decreased in comparison to ovoid applicators; on the other hand, it should be noted that the size of the reference volume also decreased significantly.

Optimisation techniques in vaginal cuff brachytherapy.

The aim of this study was to explore whether an in-house dosimetry protocol and optimisation method are able to produce a homogeneous dose distribution in the target volume, and how often optimisation is required in vaginal cuff brachytherapy. Treatment planning was carried out for 109 fractions in 33 patients who underwent high dose rate iridium-192 (Ir(192)) brachytherapy using Fletcher ovoids. Dose prescription and normalisation were performed to catheter-oriented lateral dose points (dps) within a range of 90-110% of the prescribed dose. The in-house vaginal apex point (Vk), alternative vaginal apex point (Vk'), International Commission on Radiation Units and Measurements (ICRU) rectal point (Rg) and bladder point (Bl) doses were calculated. Time-position optimisations were made considering dps, Vk and Rg doses. Keeping the Vk dose higher than 95% and the Rg dose less than 85% of the prescribed dose was intended. Target dose homogeneity, optimisation frequency and the relationship between prescribed dose, Vk, Vk', Rg and ovoid diameter were investigated. The mean target dose was 99+/-7.4% of the prescription dose. Optimisation was required in 92 out of 109 (83%) fractions. Ovoid diameter had a significant effect on Rg (p = 0.002), Vk (p = 0.018), Vk' (p = 0.034), minimum dps (p = 0.021) and maximum dps (p<0.001). Rg, Vk and Vk' doses with 2.5 cm diameter ovoids were significantly higher than with 2 cm and 1.5 cm ovoids. Catheter-oriented dose point normalisation provided a homogeneous dose distribution with a 99+/-7.4% mean dose within the target volume, requiring time-position optimisation.

Effect of bladder distention on bladder base dose in gynaecological intracavitary high dose rate brachytherapy.

The purpose of this study was to assess the impact of bladder volume on bladder base doses during gynaecological intracavitary high dose rate (HDR) brachytherapy. 42 different intracavitary HDR brachytherapy applications (tandem and ovoid, 25; ovoid, 17) were performed in 41 patients treated for cervical (n = 29) and endometrial (n = 12) cancer. The International Commission on Radiation Units and Measurements (ICRU) bladder reference point (BRP) dose and doses of 17 points selected on the bladder base were calculated using planning orthogonal radiographs taken after applicator placement with 100 ml and 270 ml bladder volumes. The effect of bladder volume on ICRU BRP and bladder base maximum point (BBMP) doses were analysed for both types of applications. Median ICRU BRP doses (in percentage of prescription dose) were 36.2% (18.2-69.8%) and 40.0% (21.0-61.8%) for ovoid applications (p = 0.13) and 34.9% (15.7-81.0%) and 33.8% (16.5-88.1%) for tandem and ovoid applications (p = 0.48) in 100 ml and 270 ml bladder volumes, respectively. Median BBMP doses were 75.1% (33.8-141.0%) and 104.0% (62.8-223.0%) for ovoid applications (p<0.001) and 116% (51.2-242.0%) and 124.0% (62.0-326%) for tandem and ovoid applications (p = 0.018) in 100 ml and 270 ml bladder volumes, respectively. Although the BBMP dose significantly increases, the ICRU BRP dose does not change with increasing bladder volume in gynaecological intracavitary HDR brachytherapy. Increasing bladder volume increases bladder base maximum dose in intracavitary gynaecological brachytherapy.

Changes in applicator positions and dose distribution between high dose rate brachytherapy fractions in cervix carcinoma patients receiving definitive radiotherapy.

This study examines the change of applicator geometry and its effect on rectal/rectum (R) and bladder (B) doses, and obtained radiobiological equivalent doses (RED), between each high dose rate (HDR) brachytherapy (BT) fraction in cervical carcinoma patients. BT using a tandem (T) and two ovoids (O) is included, and any discrepancies in applicator positions among the fractions were calculated. Whether the change of applicator position had an effect on the calculated R and B doses was analysed. Furthermore, the relationship between the size of tumour, the magnitude of displacement and the change in R and B doses was also investigated. Lastly, the changes in R and B RED were noted. The average magnitude of displacement was between 2.0 mm and 16.9 mm, showing time trend. There was no relationship between tumour size and the magnitude of discrepancy of Left O, Right O, T, R, B, and neither change in R and B doses (p>0.05). The mean differences of R and B doses were between 49-78 cGy, and 70-84 cGy, respectively. The magnitude of discrepancy and changes in doses showed no correlation (p>0.05). There were no significant differences in REDs for bladder (p = 0.8) and rectum (p = 0.2). In conclusion, there were significant differences in the applicator positions R and B and R and B doses among the fractions, which confirm the necessity of treatment planning in each HDR BT fraction. However, the total calculated R and B REDs did not show a remarkable difference.

Spinal cord ependymomas in adults: analysis of 15 cases.

This retrospective analysis was performed to examine the outcome of patients with spinal cord ependymomas treated with surgery and postoperative radiation therapy between 1982 and 1998. There were 10 male and 5 female patients, ranging from 16 to 74 years of age with a median age of 38 years. Surgery was gross total resection in 2 patients, subtotal resection in 10, biopsy in 3. All patients received radiation therapy with a total dose of 40-56 Gy. The 5 and 10 year overall survival rates were 83.3 and 83.3%, respectively. Twelve patients are still alive at a median follow-up period of 70 months. Of the 15 patients, 6 developed recurrent disease on follow-up. The median time to recurrence was 45 months (range: 24-80 months). Local failure within the initial irradiated volume occurred in 3 out of 6 patients who received less than 45 Gy and 2 out of 8 patients treated with more than 45 Gy. Four out of the six failures were salvaged with additional treatment. Re-irradiation was used as a part of salvage or sole treatment in 3 cases. The patient who was salvaged with radiation therapy only died of disease progression 41 months following recurrence and the other two who received a combination of surgery, radiotherapy or chemotherapy were still alive 57 and 30 months following relapse. The present study shows that surgery and post-operative radiation treatment for spinal ependymoma patients resulted in high survival rates. Patients with residual disease after surgery should be treated with radiation therapy with a dose of more than 45 Gy. Re-irradiation may be the treatment of choice for recurrent patients having less than complete resection or no surgery.

Adding concurrent low dose continuous infusion of cisplatin to radiotherapy in locally advanced cervical carcinoma: a prospective randomized pilot study.

The tolerability and efficacy of the continuous infusion of cisplatin during radiotherapy was studied by tumour response, survival and pelvic control, in carcinoma of the cervix. 44 patients with stage IIB-IIIB cervical carcinoma were prospectively randomized into two groups: radiation alone (control group) versus radiation plus cisplatin (study group). While there was no significant difference in diarrhoea and urinary complication scores, emesis and appetite changes were significantly greater in the study group. Tumour responses were no different at the end of the treatment and 3 months after completion of treatment. After 40 months median follow-up, 40/44 patients were assessed (one had a second primary tumour and three were lost to follow-up). Persistent disease was found in 3 patients: one in the study arm and two in the control arm. Recurrence was seen in 10 patients in the first 2 years. 5-year pelvic control rates were; 69.4% and 63.9% (p=0.7), survival rates were 52.0% and 48.9% (p=0.7) and disease-free survival rates were 67.5% and 58.7% (p=0.3) for the control and the study groups, respectively. Although the continuous infusion of cisplatin during radiotherapy was well tolerated, this additional treatment did not appear to show an improvement in pelvic control, survival, or disease-free survival.

The role of technetium-99m methoxyisobutyl isonitrile scintigraphy in suspected recurrent breast cancer.

The aim of this study was to determine the role of technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) scintigraphy in the evaluation of recurrence and metastases in breast cancer patients with mastectomy and/or radiotherapy. A prospective study was designed to assess the accuracy of 99mTc-MIBI scintigraphy in 36 patients (mean age 49 years) with suspected recurrent breast cancer. The scintigraphic studies were correlated with radiological findings and/or with histopathology. At 10-15 min after 740MBq 99mTc-MIBI injection, standard planar images were obtained in prone lateral and anterior supine views and then single-photon emission computed tomography (SPECT) imaging was performed. A whole body imaging was also performed to demonstrate distant metastatic lesions. Totally 52 lesions were evaluated which 19 of them in 9 patients were malignant, while 33 lesions in 27 patients were benign. The sensitivity was 33%, 88% and the specificity was 96%, 93% for planar and SPECT imaging, respectively in loco-regional lesions. Overall, the sensitivity and the specificity of MIBI imaging including whole body were 89%, 81%, in other conventional radiological imaging methods were 95%, 65%, respectively. 99mTc-MIBI scintigraphy using SPECT imaging may provide useful complementary information in patients with suspected recurrence breast cancer.

The role of lung perfusion imaging in predicting the direction of radiation-induced changes in pulmonary function tests.

BACKGROUND: The aim of this study was to determine whether preradiation (pre-RT) single photon emission computed tomography (SPECT) lung perfusion scans can be used to predict RT-induced changes in pulmonary function tests (PFTs). METHODS: Ninety-four patients irradiated for thoracic tumors had pre-RT SPECT lung perfusion scans. The presence of SPECT hypoperfusion distal to a central mediastinal tumor was qualitatively assessed visually without knowledge of PFT changes. Patients were grouped based on whether the diffusion capacity (DLCO) ever increased post-RT. Comparisons of patient groups were performed using 1-tailed Fisher exact tests. Patient follow-up was 6-56 months (mean, 30 months). To assess SPECT hypoperfusion objectively, the average dose to the computed tomography (CT)-defined lung was compared with the weighted-average dose (based on relative perfusion) to the SPECT-defined lung. The ratio between the CT- and SPECT-defined mean lung dose provided a quantitative assessment of hypoperfusion. The mean ratio for patients with central tumor and adjacent hypoperfusion was compared with that of the others (Wilcoxon rank-sum one-sided test). RESULTS: In patients with central tumors, 41% (9 of 22) with adjacent hypoperfusion had improvements in DLCO following radiation, versus 18% (3 of 17) of those without hypoperfusion (P = 0.11). In patients with lung carcinoma, the corresponding ratios were 40% (8 of 20) and 10% (1 of 10), respectively (P = 0.10). The mean ratio of CT dose to SPECT dose was 1.35 for patients with central tumors and adjacent hypoperfusion versus 1.16 for others (P = 0.017). CONCLUSIONS: The presence of SPECT hypoperfusion adjacent to a central mediastinal mass may identify patients likely to have improved PFTs following RT. Thus, SPECT imaging may be useful in models for predicting radiation-induced changes in PFTs.

Benefit of adjuvant radiotherapy in surgically staged stage I-II endometrial carcinoma.

AIMS AND BACKGROUND: This study was performed to determine the treatment outcomes and patterns of failure following external beam therapy in patients with pathological stage I-II endometrial carcinoma. STUDY DESIGN: Eighty-three patients with stage I-II endometrial carcinoma surgically staged who were found to have high risk factors and who received postoperative radiation therapy are the subject of this report. High risk factors were: histologic grade II-III, depth of myometrial invasion (DMI) > or =1/2, stage II, poor prognostic histology (clear cell, papillary serous cell) and lymphovascular invasion. RESULTS: Recurrences were observed in six patients. The recurrences were located in the vagina (1), lung (2), liver (1), and paraaortic lymph nodes (1). Five of the six recurrences were stage IC and II. The overall survival (OS), cause-specific survival (CSS) and disease-free survival (DFS) at five years were 82.9%, 85.0% and 81.3%, respectively. DMI, grade, age and cervical stromal invasion had a significant impact on CSS. CONCLUSION: Adjuvant radiotherapy decreases the rate of relapse in pathologically staged high-risk stage I-II endometrial carcinoma patients. After reviewing the other studies on this subject we conclude that vaginal cuff brachytherapy alone could be used in stage IA grade III and stage IB grade I-II patients because the recurrence rate is low; pelvic radiotherapy + vaginal cuff brachytherapy should be used for stage IC-II disease. Distant metastases occurred in five of our patients and represent a significant type of failure.

The effect of patient-specific factors on radiation-induced regional lung injury.

PURPOSE: To assess the impact of patient-specific factors on radiation (RT)-induced reductions in regional lung perfusion. METHODS: Fifty patients (32 lung carcinoma, 7 Hodgkin's disease, 9 breast carcinoma and 2 other thoracic tumors) had pre-RT and > or = 24-week post-RT single photon emission computed tomography (SPECT) perfusion images to assess the dose dependence of RT-induced reductions in regional lung perfusion. The SPECT data were analyzed using a normalized and non-normalized approach. Furthermore, two different mathematical methods were used to assess the impact of patient-specific factors on the dose-response curve (DRC). First, DRCs for different patient subgroups were generated and compared. Second, in a more formal statistical approach, individual DRCs for regional lung injury for each patient were fit to a linear-quadratic model (reduction = coefficient 1 x dose + coefficient 2 x dose2). Multiple patient-specific factors including tobacco history, pre-RT diffusion capacity to carbon monoxide (DLCO), transforming growth factor-beta (TGF-beta), chemotherapy exposure, disease type, and mean lung dose were explored in a multivariate analysis to assess their impact on the coefficients. RESULTS: None of the variables tested had a consistent impact on the radiation sensitivity of regional lung (i.e., the slope of the DRC). In the formal statistical analysis, there was a suggestion of a slight increase in radiation sensitivity in the dose range >40 Gy for nonsmokers (vs. smokers) and in those receiving chemotherapy (vs. no chemotherapy). However, this finding was very dependent on the specific statistical and normalization method used. CONCLUSION: Patient-specific factors do not have a dramatic effect on RT-induced reduction in regional lung perfusion. Additional studies are underway to better clarify this issue. We continue to postulate that patient-specific factors will impact on how the summation of regional injury translates into whole organ injury. Refinements in our methods to generate and compare SPECT scans are needed.

Prognostic factors in stage IB-IIA cervical carcinomas treated with postoperative radiotherapy.

PURPOSE: This study investigated the prognostic significance of age, stage, tumor size, pelvic lymph node metastasis (PLM), surgical margin invasion, overall radiotherapy time (ORT), and interval between radiotherapy and surgery (IRS) in stage IB-IIA cervical carcinoma. METHOD AND MATERIALS: 100 patients treated with radical hysterectomy and postoperative radiotherapy were evaluated retrospectively. RESULTS: The 5-yr overall survival (OS), disease-free survival (DFS), and pelvic control rate (PC) were 83.6%, 82.8%, and 91.8%, respectively. PLM (p=0.008), IRS (p=0.01), ORT (p=0.007), and tumor size (p=0.028) were found to be significant on PC. PLM (p=0.04), ORT (p=0.04), and IRS (p=0.001) were significant on OS. PLM was significant (p=0.04) and IRS was marginally significant (p=0.06) on DFS. After multivariate analysis, PLM was significant on OS, DFS and PC. Recurrences were seen in 14 patients. CONCLUSION: According to this study PLM, IRS, and ORT are the most important prognostic factors. Recurrences outside the radiation volume leads to treatment failure.

Treatment results and prognostic factors in inoperable carcinoma of the cervix treated with external plus high dose brachytherapy.

Patients with inoperable carcinoma of the cervix treated with external plus high dose rate brachytherapy (HDRB), between 1988 and 1995 were evaluated retrospectively. According to stage, 5 year survival rates were 67.3% in stage IIb and 52.6% in stage III (P = 0001) and disease free survival (DFS) rates were 54.0% in stage IIb and 43.9% in stage III (P = 0.01). The following parameters were studied: age; stage; external beam dose; brachytherapy dose; total dose to point A; tumor mass; tumor response rate; bilateral or unilateral invasion of parametria in stage IIb; and bilateral or unilateral invasion of pelvic wall in stage IIIb; and the existence of hydronephrosis. The only significant parameter of 5 year survival and local control was tumor mass (P = 0.003).

Factors affecting long-term outcome of irradiation in carcinoma of the vagina.

OBJECTIVE: This report evaluates prognostic and technical factors affecting outcome of patients with primary carcinoma of the vagina treated with definitive radiation therapy. METHODS AND MATERIALS: A retrospective analysis was performed on records of 212 patients with histologically confirmed carcinoma of the vagina treated with irradiation. RESULTS: Tumor stage was the most significant prognostic factor; actuarial 10-year disease-free survival was 94% for Stage 0 (20 patients), 80% for Stage I (59 patients), 55% for Stage IIA (63 patients), 35% for Stage IIB (34 patients), 38% for Stage III (20 patients), and 0% for Stage IV (15 patients). All in situ lesions except one were controlled with intracavitary therapy. Of the patients with Stage I disease, 86% showed no evidence of vaginal or pelvic recurrence; most of them received interstitial or intracavitary therapy or both, and the addition of external-beam irradiation did not significantly increase survival or tumor control. In Stage IIA (paravaginal extension) and IIB (parametrial involvement) 66% and 56% of the tumors, respectively, were controlled with a combination of brachytherapy and external-beam irradiation; 13 of 20 (65%) Stage III tumors were controlled in the pelvis. Four patients with Stage IV disease (27%) had no recurrence in the pelvis. The total incidence of distant metastases was 13% in Stage I, 30% in Stage IIA, 52% in Stage IIB, 50% in Stage III, and 47% in Stage IV. The dose of irradiation delivered to the primary tumor or the parametrial extension was of relative importance in achieving successful results. In patients with Stage I disease, brachytherapy alone achieved the same local tumor control (80-100%) as in patients receiving external pelvic irradiation (78-100%) as well. In Stage II and III there was a trend toward better tumor control (57-80%) with combined external irradiation and brachytherapy than with the latter alone (33-50%) (p = 0.42). The incidence of grade 2-3 complications (12%) correlated with the stage of the tumor and type of treatment given. CONCLUSION: Radiation therapy is an effective treatment for patients with vaginal carcinoma, particularly Stage I. More effective irradiation techniques, including optimization of dose distribution combining external irradiation and interstitial brachytherapy in tumors beyond Stage I, are necessary to enhance locoregional tumor control. The high incidence of distant metastases emphasizes the need for earlier diagnosis and effective systemic cytotoxic agents to improve survival in these patients.

Irradiation in carcinoma of the vulva: factors affecting outcome.

PURPOSE: This report reviews the increasing role of radiation therapy in the management of patients with histologically confirmed vulvar carcinoma, based on a retrospective analysis of 68 patients with primary disease (2 in situ and 66 invasive) and 18 patients with recurrent tumor treated with irradiation alone or combined with surgery. METHODS AND MATERIALS: Of the patients with primary tumors, 14 were treated with wide local excision plus irradiation, 19 received irradiation alone after biopsy, 24 were treated with radical vulvectomy followed by irradiation to the operative fields and inguinal-femoral/pelvic lymph nodes, and 11 received postoperative irradiation after partial or simple vulvectomy. The 18 patients with recurrent tumors were treated with irradiation alone. Indications and techniques of irradiation are discussed in detail. RESULTS: In patients treated with biopsy/local excision and irradiation, local tumor control was 92% to 100% in Stages T1-3N0, 40% in similar stages with N1-3, and 27% in recurrent tumors. In patients treated with partial/radical vulvectomy and irradiation, primary tumor control was 90% in patients with T1-3 tumors and any nodal stage, 33% in patients with any T stage and N3 lymph nodes, and 66% with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for T1N0, 62% for T2-3N0, 30% for T1-3N1 disease, and 11 % for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 tumors. Four of 18 patients (22%) treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and irradiation. In patients with T1-2 tumors treated with biopsy/wide tumor excision and irradiation with doses under 50 Gy, local tumor control was 75% (3 of 4), in contrast to 100% (13 of 13) with 50.1 to 65 Gy. In patients with T3-4 tumors treated with local wide excision and irradiation, tumor control was 0% with doses below 50 Gy (3 patients) and 63% (7 of 11) with 50.1 to 65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and irradiation, local tumor control was 83% (14 of 17), regardless of dose level, and in T3-4 tumors, it was 62% (5 of 8) with 50 to 60 Gy and 80% (8 of 10) with doses higher than 60 Gy. The differences are not statistically significant. There was no significant dose response for tumor control in the inguinal-femoral lymph nodes; doses of 50 Gy were adequate for elective treatment of nonpalpable lymph nodes, and 60 to 70 Gy controlled tumor growth in 75% to 80% of patients with N2-3 nodes when administered postoperatively after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess. CONCLUSIONS: Irradiation is playing a greater role in the management of patients with carcinoma of the vulva; combined with wide local tumor excision or used alone in T1-2 tumors, it is an alternative treatment to radical vulvectomy, with significantly less morbidity. Postradical vulvectomy irradiation in locally advanced tumors improves tumor control at the primary site and the regional lymphatics in comparison with reports of surgery alone.