Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer.

PURPOSE: The purpose of this work was to compare toxicity and cancer control between patients with prostate cancer treated using three-dimensional conformal radiotherapy (3D-CRT) and those treated using intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: A total of 553 patients with prostate cancer were treated with 3D-CRT 70-74 Gy (3D-CRT 70, 3D-CRT 74) or IMRT 78-82 Gy (IMRT 78, IMRT/SIB 82). Late toxicity was scored according to FC-RTOG/LENT criteria. Biochemical failure was defined using the Phoenix and ASTRO definitions. RESULTS: The 5-year risk of grade 2-4 genitourinary toxicity was 26.3 % (3D-CRT 70), 27.2 % (3D-CRT 74), 17.3 % (IMRT 78), and 25.1 % (IMRT/SIB 82) without statistical differences. The 5-year risk of grade 2-4 gastrointestinal toxicity was 19.4 % (3D-CRT 70), 42.1 % (3D-CRT 74), 20.5 % (IMRT 78), and 26.6 % (IMRT/SIB 82). The differences between 3D-CRT 74 and 3D-CRT 70 and between 3D-CRT 74 and IMRT 78 were statistically significant (log rank p = 0.03). The 5-year Phoenix PSA relapse-free survival (PSA-RFS) in low-risk, intermediate-risk, and high-risk patients treated using 3D-CRT were 89.4, 65.5, and 57.8 %, respectively. Patients treated with IMRT achieved the following results: 90.9, 89.4, and 83.9 %. Clinical relapse-free survival (C-RFS) in patients treated using 3D-CRT vs. IMRT for the aforementioned groups were 94.7 vs. 100 %, 86.8 vs. 98.6 %, and 84.4 vs. 94.5 %. Disease-free survival (DFS) for patients treated using 3D-CRT were 83.1, 70.9, and 71.5 %. The IMRT group reached 95.8, 89.1, and 87.6 %. The PSA-RFS for intermediate- and high-risk patients were statistically significant, while C-RFS and DFS were marginally better. CONCLUSION: Dose escalation with IMRT was associated with improved cancer control in intermediate- and high-risk patients in comparison with 3D-CRT, without compromising toxicity.

Utilization of cone beam CT for reconstruction of dose distribution delivered in image-guided radiotherapy of prostate carcinoma - bony landmark setup compared to fiducial markers setup.

The purpose of this study was to compare two different styles of prostate IGRT: bony landmark (BL) setup vs. fiducial markers (FM) setup. Twenty-nine prostate patients were treated with daily BL setup and 30 patients with daily FM setup. Delivered dose distribution was reconstructed on cone-beam CT (CBCT) acquired once a week immediately after the alignment. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed 1 cm safety margin. Alternative plans assuming smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with initial ones. While the margin reduction in case of BL setup makes the prostate coverage significantly worse (p = 0.0003, McNemar's test), in case of FM setup with the reduced 7 mm margin, the prostate coverage is even better compared to BL setup with 10 mm margin (p = 0.049, Fisher's exact test). Moreover, partial volumes of organs at risk irradiated with a specific dose can be significantly lowered (p < 0.0001, unpaired t-test). Reducing of safety margin is not acceptable in case of BL setup, while the margin can be lowered from 10 mm to 7 mm in case of FM setup.

Utilization of cone-beam CT for offline evaluation of target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment.

AIM: To assess target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment and to assess possibility of safety margin reduction. BACKGROUND: Implementation of IGRT should influence safety margins. Utilization of cone-beam CT provides current 3D anatomic information directly in irradiation position. Such information enables reconstruction of the actual dose distribution. MATERIALS AND METHODS: Seventeen prostate patients were treated with daily bony anatomy image-guidance. Cone-beam CT (CBCT) scans were acquired once a week immediately after bony anatomy alignment. After the prostate, seminal vesicles, rectum and bladder were contoured, the delivered dose distribution was reconstructed. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed a 1 cm safety margin. Alternative plans assuming a smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with the initial ones. Rectal and bladder volumes irradiated with doses higher than 75 Gy, 70 Gy, 60 Gy, 50 Gy and 40 Gy were analyzed. RESULTS: In 12% of reconstructed plans the prostate coverage was not sufficient. The prostate underdosage was observed in 5 patients. Coverage of seminal vesicles was not satisfactory in 3% of plans. Most of the target underdosage corresponded to excessive rectal or bladder filling. Evaluation of alternative plans assuming a smaller 7 mm margin revealed 22% and 11% of plans where prostate and seminal vesicles coverage, respectively, was compromised. These were distributed over 8 and 7 patients, respectively. CONCLUSION: Sufficient dose coverage of target volumes was not achieved for all patients. Reducing of safety margin is not acceptable. Initial rectal and bladder volumes cannot be considered representative for subsequent treatment.

Dose escalation in prostate radiotherapy up to 82 Gy using simultaneous integrated boost: direct comparison of acute and late toxicity with 3D-CRT 74 Gy and IMRT 78 Gy.

PURPOSE: To compare acute and late toxicity after three-dimensional conformal radiotherapy to the prostate to 74 Gy (3D-CRT) with intensity-modulated radiotherapy to 78 Gy (IMRT 78) and IMRT using simultaneous integrated boost to 82 Gy (IMRT/SIB 82). PATIENTS AND METHODS: 94 patients treated with 3D-CRT to the prostate and base of seminal vesicles to 74 Gy represented the first group. The second group consisted of 138 patients subjected to IMRT covering the prostate and base of seminal vesicles to 78 Gy. The last group was treated with IMRT using SIB. The prescribed doses were 82 Gy and 73.8 Gy in 42 fractions to the prostate and seminal vesicles. Late toxicity was prospectively scored according to the RTOG/FC-LENT scale. RESULTS: Acute gastrointestinal toxicity >or= grade 2 occurred in 35.1% of patients treated with 3D-CRT, in 16% subjected to IMRT 78, and in 7.7% receiving IMRT/SIB 82. Acute genitourinary toxicity >or= grade 2 was observed in 26.6% (3D-CRT), 33% (IMRT 78), and 30.7% (IMRT/SIB 82). At 3 years, the estimated cumulative incidence of grade 3 late gastrointestinal toxicity was 14% for 3D-CRT, 5% for IMRT 78, and 2% for IMRT/SIB 82. The difference became significant (log rank p = 0.02). The estimated cumulative incidence of grade 3 late genitourinary toxicity was 9% (3D-CRT), 7% (IMRT 78), and 6% (IMRT/SIB 82) without statistical differences (log rank p = 0.32) CONCLUSION: SIB enables dose escalation up to 82 Gy with a lower rate of gastrointestinal toxicity grade 3 in comparison with 3D-CRT up to 74 Gy.

Late toxicity after conformal and intensity-modulated radiation therapy for prostate cancer: impact of previous surgery for benign prostatic hyperplasia.

OBJECTIVES: To retrospectively compare late toxicity of conventional-dose three-dimensional conformal radiation therapy (3D-CRT) and high-dose intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODS: A total of 340 patients with T1-3 prostate cancer were treated with 3D-CRT (n = 228) and IMRT (n = 112). The median follow-up time was 5.9 years and 3.0 years, respectively. The prescription dose was 70 Gy for 3D-CRT and 78 Gy for IMRT. Late gastrointestinal (GI) and genitourinary (GU) toxicities were graded according to the Fox Chase modification of the Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. RESULTS: There was no difference between 3D-CRT and IMRT in the incidence of GI and GU toxicity at 3 years. On multivariate analysis, transurethral resection of prostate/open transvesical prostatectomy (TURP/TVPE) for benign prostatic hyperplasia, carried out before radiotherapy, significantly increased the risk of Grade >or=2 GU toxicity (risk ratio 1.88). Among patients who experienced TURP/TVPE, the 5-year actuarial likelihood of Grade 2-3 urinary incontinence was 23%, compared with 9% for those without prostate surgery (P = 0.01). CONCLUSIONS: Tolerance of 3D-CRT and IMRT was similar, despite the use of high radiation dose with IMRT. Previous TURP/TVPE increased the risk of GU toxicity.

Solitary extramedullary plasmacytoma in the oropharynx: advantages of intensity-modulated radiation therapy.

We report a case of a 59-year-old man with solitary extramedullary plasmacytoma in his oropharynx. Because the diagnosis is rare and there is only limited experience in the literature based on retrospective data, the optimal planning target volume and optimal dose of radiation therapy (RT) are still controversial. The frequently discussed problem is the necessity of first echelon lymph node irradiation because it is associated with a higher rate of complications such as xerostomia caused by damage to salivary glands. In order to prevent late toxicity, intensity-modulated RT with the use of simultaneous integrated boost and parotid salivary gland sparing was used in this patient's treatment. The RT was performed in 23 identical fractions, the primary tumor region was irradiated with a dose of 46 Gy and the first echelon lymph node region with the risk of subclinical disease with a dose of 41.4 Gy; the dose per fraction was 2 Gy and 1.8 Gy, respectively. The patient is alive and well > 20 months after the irradiation, without any evidence of disease. Parotid gland function remained intact, and no xerostomia occurred. This is the first report of the use of intensity-modulated RT with parotid gland sparing in the treatment of solitary extramedullary plasmacytoma in the head and neck region.

The technique of intensity-modulated radiotherapy in the treatment of cholangiocarcinoma.

AIMS AND BACKGROUND: Conventional radiotherapy in inoperable cholangiocarcinoma is limited by radiotolerance of the surrounding tissues. The aim of our dosimetric study was an evaluation of intensity-modulated radiotherapy in the treatment of inoperable bile duct carcinoma. METHODS: Four patients with inoperable cholangiocarcinoma treated by self-expandable stent placed to the biliary tree and radiotherapy were studied. The rotational technique, conformal 3D BOX technique and intensity-modulated radiotherapy plan were compared. Dose volume histograms and the normal tissue complication probability concept were used for comparison. The stent was used for target motion verification. RESULTS: The intensity-modulated radiotherapy plans showed favorable dose distribution in planning target volume and remarkable sparing of organs at risk. CONCLUSIONS: The intensity-modulated radiotherapy technique in bile duct carcinomas deserves further research and clinical evaluation.

IMRT with the use of simultaneous integrated boost in treatment of head and neck cancer: acute toxicity evaluation.

Acute toxicity has been evaluated in head and neck cancer patients treated with intensity-modulated radiotherapy using simultaneous integrated boost (SIB-IMRT). The basis of the treatment protocol is an irradiation in 30 fractions with a total dose: 66 Gy to the region of macroscopic tumor, 60 Gy to the region of high-risk subclinical disease and 54 Gy to the region of low-risk subclinical disease. Between December 2003 and September 2005, 38 patients with carcinoma of different locations in the head and neck region were irradiated. Five patients underwent concurrent chemotherapy (weekly cisplatin). Acute toxicity was evaluated according to Radiation Therapy Oncology Group toxicity scale for skin, mucous membrane, salivary glands, pharynx and esophagus and larynx. All 38 patients completed the therapy without urgency of interruption due to acute toxicity of radiotherapy. No patient experienced grade 4 toxicity. More severe toxicity was observed in patients with concurrent chemotherapy. The results confirm that the irradiation according to our SIB-IMRT protocol is a therapy with acceptable toxicity and there is a space for radiobiological enhancement of this regimen by concurrent chemotherapy, e.g. weekly cisplatin.

Comparison of rectal dose-volume constraints for IMRT prostate treatment planning.

The purpose of this paper is to compare different sets of rectal dose-volume constraints and to develop input criteria for the intensity-modulated radiation therapy (IMRT) of prostate cancer. The IMRI treatment plans were created using Varian planning system (CadPlan with Helios module) for ten patients with localized prostate cancer (isocenter dose 78 Gy). The posterior portion of rectum was contoured as an extra volume (help volume). Three sets of input parameters for rectum with gradually increasing priorities (25-50-75-90) were designed for the inverse treatment planning: 1. dose-volume constraints allowing no more than 50, 40, 20 and 10% of the rectum volume be irradiated to 50, 60, 70, and 75 Gy, respectively-volume-based plans, priorities 25-90 (V25-90 plans); 2. maximum dose constraint of 74.1 Gy for rectum-plans with limited maximum reactal dose, priorities 25-90 (M25-90 plans); 3. maximum dose constraint of 50 Gy for the help volume-plans with limited maximum dose for the help volume, priorities 25-90 (H25-90 plans). Dose homogeneity in the planning target volume (PTV) and the rectal volumes (RV) irradiated to 50, 60, 70, and 75 Gy (RV 50-75 Gy) were recorded. Rectum sparing improved for all the plans with increasing priority. While the M plans had the lowest RV 75 Gy values, the H plans gave the minimum RV 50-70 Gy values. Plans were considered acceptable if at least 98% of the PTV was treated to 95% of the prescribed dose. In particular plan groups, the V75, M75, and H50 plans, together with the V50+M75 and H50+M75 combined plans, satisfied this condition and yielded the lowest rectal doses. The H50+M75 combined plan allowed optimal sparing of rectum (RV 50 Gy 51.6%, RV 60 Gy 38.5%, RV 70 Gy 26.0%, and RV 75 Gy 9.1%, respectively). An optima set of dose-based rectal constraints (maximum rectal dose 74.1 Gy, maximum help volume dose 50 Gy) has been developed for Varian planning software. These parameters will constitute a starting point for the prostate IMRT plan optimization.

[Intensity-modulated radiotherapy in the treatment of thyroid cancer]. / Radioterapie s modulovanou intenzitou v lécbe karcinomu stítné zlázy.

The main problem of the conventional radiotherapy in postoperative or curative irradiation in thyroid cancer is to achieve a sufficient dose in the planning target volume with acceptable dose distribution homogeneity and at the same time not to exceed tolerance doses in the organs of risk. Our study presents the advantages of intensity-modulated radiotherapy over conventional radiotherapy on an example of dosimetric comparisons of isodose plans of three patients treated at our department. The intensity-modulated radiotherapy in thyroid cancer offers an improvement of dose homogeneity and better sparing of organs at risk (spinal cord and lungs). Furthermore, dose escalation is feasible in the whole initial planning target volume up to 60 Gy with a simultaneous sparing of healthy tissues and organs at risk.

High-dose rate brachytherapy in the treatment of penile carcinoma--first experience.

PURPOSE: Interstitial low-dose rate brachytherapy (BRT) allows a conservative treatment of T1-T2 penile carcinoma. High-dose rate (HDR) BRT is often considered as a dangerous method for interstitial implants because of higher risk of complications. However, numerous reports suggest that results of HDR-BRT may be comparable to low-dose rate BRT. There are no data available in the literature regarding HDR interstitial BRT for carcinoma of the penis. METHODS AND MATERIALS: Ten patients with early penile carcinoma were treated by interstitial hyperfractionated HDR-BRT at the dose of 18 times 3Gy twice daily between years 2002 and 2009. Breast interstitial BRT template was used for fixation and precise geometry reconstruction of stainless hollow needles. RESULTS: Median followup was 20 months. Our BRT technique and fractionation schedule was well tolerated by all patients. Acute reaction consisted predominantly of penis edema and Grade 2 radiation mucositis that dissolved during 8 weeks after the treatment. We neither observed any postradiation necrosis nor urethral stenosis. The worst late side effects recorded were mild telanagiectasias in the treatment region. At the last followup, all patients were alive without evidence of the tumor and with fully functional organ. CONCLUSIONS: Hyperfractionated interstitial HDR-BRT with 18 times 3 Gy per fraction twice daily is a promising method in selected patients of penile carcinoma and deserves further evaluation in a larger prospective study.

High-dose-rate interstitial brachytherapy for the treatment of penile carcinoma.

BACKGROUND: Interstitial low-dose-rate (LDR) brachytherapy allows conservative treatment of T1-T2 penile carcinoma. High dose-rate (HDR) is often considered to be dangerous for interstitial implants because of a higher risk of complications, but numerous reports suggest that results may be comparable to LDR. Nevertheless, there are no data in the literature available regarding HDR interstitial brachytherapy for carcinoma of the penis. CASE REPORT: A 64-year-old man with T1 N0 M0 epidermoid carcinoma of the glans is reported. Interstitial HDR brachytherapy was performed using the stainless hollow needle technique and a breast template for fixation and good geometry. The dose delivered was 18 x 3 Gy twice daily. RESULTS: After 232 days from brachytherapy, the patient was without any evidence of the tumor, experienced no serious radiation-induced complications, and had a fully functional organ. CONCLUSION: HDR interstitial brachytherapy is feasible in selected case of penis carcinoma, when careful planning and small single fractions are used.

Prognostic impact of hemoglobin level prior to radiotherapy on survival in patients with glioblastoma.

PURPOSE: To evaluate prognostic factors in patients with glioblastoma treated with postoperative or primary radiotherapy. PATIENTS AND METHODS: From 1989 to 2000, a total of 100 patients underwent irradiation as part of their initial treatment for glioblastoma. All patients had undergone surgery or biopsy followed by conventional external-beam radiotherapy. 85 patients who received the planned dose of irradiation (60 Gy in 30 fractions) were analyzed for the influence of prognostic factors. 73/85 (86%) of patients were given postoperative irradiation, while 12/85 (14%) of patients were primarily treated with radiotherapy after biopsy. RESULTS: The median overall survival was 10.1 months (range, 3.7-49.8 months), the 1- and 2-year survival rates were 41% and 5%, respectively. Univariate analysis revealed age < or = 55 years (p < 0.001), pre-radiotherapy hemoglobin (Hb) level > 12 g/dl (p = 0.009), and pre-radiotherapy dose of dexamethasone < or = 2 mg/day (p = 0.005) to be associated with prolonged survival. At multivariate analysis, younger age (p < 0.001), higher Hb level (p = 0.002), lower dose of dexamethasone (p = 0.026), and a hemispheric tumor location (p = 0.019) were identified as independent prognostic factors for longer survival. The median survival for patients with an Hb level > 12 g/dl was 12.1 months compared to 7.9 months for those with a lower Hb level. Contingency-table statistics showed no significant differences for the two Hb groups in the distribution of other prognostic factors. CONCLUSION: The results indicate that lower Hb level prior to radiotherapy for glioblastoma can adversely influence prognosis. This finding deserves further evaluation.