Hyperthermia combined with radiation in treatment of locally advanced prostate cancer is associated with a favourable toxicity profile.

PURPOSE: Hyperthermia is used to treat several pelvic tumours. An important step in establishing a broader role for hyperthermia in treatment of prostate cancer is verification of an acceptable toxicity profile. In this report, short- and long-term toxicity profiles of a completed phase II trial of transrectal ultrasound hyperthermia combined with radiation in treatment of locally advanced prostate cancer are presented. METHODS AND MATERIALS: Thirty-seven patients enrolled on a phase II study of external beam radiation +/- androgen suppression with two transrectal ultrasound hyperthermia treatments were assessed for short- and long-term toxicity. Prostatic and anterior rectal wall temperatures were monitored. Rectal wall temperatures were limited to 40 degrees C (19 patients), 41 degrees C (three patients) and 42 degrees C (15 patients). Univariate logistic regression was used to estimate the log hazard of developing NCI CTC Grade 2 toxicity based on temperature parameters. Hazard ratios, 95% confidence intervals, p-values for statistical significance of each parameter and proportion of variability explained for each of the parameters were calculated. RESULTS: Median follow-up was 42 months. Both short- and long-term GI toxicity were limited to grade 2 or less. Acute grade 2 proctitis was greater for patients with allowable rectal wall temperature of >40 degrees C. Eleven of 18 patients in this group had acute grade 2 proctitis vs three of 19 patients with rectal wall temperatures limited to 40 degrees C (p = 0.004). Long-term grade 2 GI and GU toxicity occurred in 5% and 19% of patients. No late grade 3 or greater toxicity occurred. Late GI and GU toxicity were not associated with the allowable rectal wall temperature. CONCLUSION: Transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer is safe and well tolerated.     

A new phase III trial for treatment of carcinoma of the cervix

This report describes patient tolerance and toxicity of a transrectal ultrasound hyperthermia system used with external beam radiation therapy in treatment of locally advanced prostate cancer. Nine patients with clinical T2B-T3B (4^th edition AJCC criteria) disease received external beam radiation therapy, with two hyperthermia treatments scheduled at least 1 week apart during the first 4 weeks of radiation. Five patients also received hormonal therapy. Interstitial and anterior rectal wall thermometry were performed. Median temperature for each treatment (T₅₀) was 40.8°C and mean CEM T₉₀ = 43°C was 3.4 min. Rectal wall temperature was maintained at ≤40°C. Treatment duration was limited in three of 17 sessions due to positional discomfort which was alleviated with light IV sedation and use of a `New Life' mattress (Comfortex, Inc. Winoba, MN, USA). Acute toxicity was limited to NCI common toxicity criteria grade 1 and no excess toxicity was noted with full course radiation therapy +/? hormonal therapy. These findings are consistent with those reported in a previous phase I trial assessing this device. Given the favourable toxicity profile demonstrated to date, modification of treatment parameters for this ongoing phase II study have been instituted that should further the efficacy of transrectal ultrasound hyperthermia for treatment of prostate cancer.     

Association of rectal toxicity with thermal dose parameters in treatment of locally advanced prostate cancer with radiation and hyperthermia

PURPOSE: Although hyperthermia has been used for more than two decades in the treatment of pelvic tumors, little is known about the potential impact of heat on rectal toxicity when combined with other treatment modalities. Because rectal toxicity is a concern with radiation and may be exacerbated by hyperthermia, definition of the association of thermal dose parameters with rectal toxicity is important. In this report, we correlate rectal toxicity with thermal dose parameters for patients treated with hyperthermia and radiation for prostate cancer. METHODS AND MATERIALS: Thirty patients with T2b-T3b disease (1992 American Joint Committee On Cancer criteria) enrolled in a Phase II study of external beam radiation +/- androgen-suppressive therapy with two transrectal ultrasound hyperthermia treatments were assessed for rectal toxicity. Prostatic and anterior rectal wall temperatures were monitored for all treatments. Rectal wall temperatures were limited to 40 degrees C in 19 patients, 41 degrees C in 3 patients, and 42 degrees C in 8 patients. Logistic regression was used to estimate the log hazard of developing National Cancer Institute Common Toxicity Criteria Grade 2 toxicity based on temperature parameters. The following were calculated: hazard ratios, 95% confidence intervals, p values for statistical significance of each parameter, and proportion of variability explained for each parameter. RESULTS: Gastrointestinal toxicity was limited to Grade 2. The rate of acute Grade 2 proctitis was greater for patients with an allowable rectal wall temperature of >40 degrees C. In this group, 7 of 11 patients experienced acute Grade 2 proctitis, as opposed to 3 of 19 patients in the group with rectal wall temperatures limited to 40 degrees C (p = 0.004). Preliminary assessment of long-term toxicity revealed no differences in toxicity. Hazard ratios for acute Grade 2 proctitis for allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax were 9.33 (p = 0.01), 3.66 (p = 0.03), and 2.29 (p = 0.08), respectively. A model combining these three parameters explained 48.6% of the variability among groups. CONCLUSION: Rectal toxicity correlates with maximum allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax for patients undergoing transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer. Further definition of this association of thermal dose parameters with rectal toxicity in treatment of pelvic malignancies with hyperthermia should advance the goal of delivering thermal therapy in an effective yet safe manner.     

Feasibility and patient tolerance of a novel transrectal ultrasound hyperthermia system for treatment of prostate cancer.

This report describes patient tolerance and toxicity of a transrectal ultrasound hyperthermia system used with external beam radiation therapy in treatment of locally advanced prostate cancer. Nine patients with clinical T2B-T3B (4th edition AJCC criteria) disease received external beam radiation therapy, with two hyperthermia treatments scheduled at least 1 week apart during the first 4 weeks of radiation. Five patients also received hormonal therapy. Interstitial and anterior rectal wall thermometry were performed. Median temperature for each treatment (T50) was 40.8 degrees C and mean CEM T90 = 43 degrees C was 3.4 min. Rectal wall temperature was maintained at < or = 40 degrees C. Treatment duration was limited in three of 17 sessions due to positional discomfort which was alleviated with light IV sedation and use of a 'New Life' mattress (Comfortex, Inc. Winoba, MN, USA). Acute toxicity was limited to NCI common toxicity criteria grade 1 and no excess toxicity was noted with full course radiation therapy +/- hormonal therapy. These findings are consistent with those reported in a previous phase I trial assessing this device. Given the favourable toxicity profile demonstrated to date, modification of treatment parameters for this ongoing phase II study have been instituted that should further the efficacy of transrectal ultrasound hyperthermia for treatment of prostate cancer.     

Intensity-modulated radiation therapy (IMRT) for prostate cancer with the use of a rectal balloon for prostate immobilization: acute toxicity and dose-volume analysis

PURPOSE: To report acute toxicity and to evaluate the relationship between dose-volume effects and acute toxicity in patients with localized prostate cancer, treated with intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Acute toxicity (both lower gastrointestinal [GI] and genito-urinary [GU]) in 100 patients treated with IMRT definitively to a prescribed dose of 70 Gy were assessed using RTOG scoring criteria. A rectal balloon was used for prostate immobilization. Mean doses to seminal vesicles, prostate, bladder, and rectum were recorded. Average irradiated bladder and rectal volumes above 65, 70, and 75 Gy were assessed. A relationship between dose volume and clinical toxicity was evaluated. All patients completed the full duration of acute toxicity assessment. RESULTS: Mean doses to the prostate and seminal vesicles were 75.8 and 73.9 Gy. This represents a moderate dose escalation. Acute GI toxicity profile was very favorable. Eleven percent and 6% of the patients had grade 1 and 2 GI toxicity, respectively, while 83% had no GI complaint. For GU complaints, 38% and 35% had grade 1 and 2 toxicity, respectively, while 27% had no complaints. There was no grade 3 or higher acute GI or GU toxicity. Mean doses to the bladder were 22.8, 23.4, and 26.1 Gy for grade 0, 1, and 2 GU toxicity, respectively (p = 0.132). There is no statistically significant relationship between acute GU toxicity and the bladder volume receiving > 65 Gy, > 70 Gy, or > 75 Gy. In evaluating acute GI toxicity, there are very few grade 1 and 2 events. No relationship was found between acute rectal toxicity and mean rectal dose or irradiated rectal volumes receiving more than 65, 70, and 75 Gy. CONCLUSION: The findings are important with regard to the safety of IMRT, especially in reducing acute GI toxicity. Dose escalation with IMRT using a prostate immobilization technique is feasible. The findings are also important because they contribute to the clinical and dosimetric correlation aspect in the use of IMRT to treat prostate cancer. A larger cohort may be needed to determine if there is a relationship between acute GU toxicity and (a) mean bladder dose and (b) irradiated bladder volume receiving > 65 Gy, > 70 Gy, or > 75 Gy. A larger cohort of patients treated to a higher dose may be needed to show a relationship between dose volume and acute GI toxicity.     

前列腺癌大分割调强放疗副反应初步分析

目的 分析前列腺癌大分割照射患者的早期和晚期副反应,初步探讨副反应的影响因素.方法 2006-2008年间37例前列腺痛患者接受大分割调强放疗(IMRT).13例临床靶体积(CTV)包括前列腺±精囊或术后瘤床,24例包括前列腺、精囊(或术后瘤床)和盆腔淋巴引流区.分次照射剂量为2.3～2.8 Gy(2.7 Gy占26例).95%PTV处方剂量前列腺精囊为62.5～75.0 Gy,盆腔为50.0 Gy.结果 全组中位随访时间为14个月.早期胃肠反应发生率0级38%,1级2,4%,2级35%,3级3%;直肠V50>27%与V55>20%的≥1级早期直肠反应发生率不同(P<0.05).早期泌尿系统反应发生率0级30%,1级68%,2级0和3级3%;膀胱V60<10%与V60>10%的≥1级泌尿系统反应发生率也不同(X2=6.02,P=0.038).晚期直肠反应发生率0级70%,1级24%,2级5%,无3、4级反应;直肠V65<10%与V65>10%的≥1级晚期胃肠反应发生率不同(X2=5.58,P=0.020).晚期泌尿系统反应发生率0级38%,1级49%,2级11%,3级3%,无4级反应;膀胱平均剂量>40Gy、V40>32%与V50>29%的≥2级晚期泌尿系统反应发生率均不同.结论 前列腺癌大分割IMRT初步研究结果 显示急件和晚期副反应均在可接受范围内.     

Late toxicity after intensity modulated and image guided radiation therapy for localized prostate cancer and post-prostatectomy patients

PurposeTo examine late gastrointestinal (GI) and genitourinary (GU) toxicity profiles of patients treated for prostate cancer either definitively or post-prostatectomy with both intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT).Methods and MaterialsA total of 333 patients treated definitively and 104 patients treated postoperatively with IMRT and varying IGRT techniques were retrospectively examined to evaluate GI and GU toxicity profiles > 1 year from treatment. Available dosimetric data were used for correlative analysis.ResultsThe median follow-up time for the definitive patients was 41 months and the median follow-up time for the post-prostatectomy patients was 33 months. No late grade 4 or 5 GI or GU toxicities were observed. For definitive patients, the rates of grade ≥ 2 GI and GU toxicity at 3 years were 4.9% and 4.5%, respectively. In the postoperative cohort the rate of grade > 2 GU toxicity was 11.6%, with no grade ≥ 2 GI toxicity. In the definitive cohort's Cox proportional hazards regression univariate analysis, use of anticoagulation was significantly associated with GI toxicity and age, bladder V50 and IGRT modality were associated with GU toxicity, and only age remained significant in the multivariate model. In univariate analysis for the postoperative cohort, no dosimetric value correlated with GU toxicity, nor did age or time from radical prostatectomy to radiation.ConclusionsIMRT with IGRT achieved low rates of GI and GU toxicity in the definitive and postoperative setting.     

Diabetes mellitus: a predictor for late radiation morbidity

PURPOSE: Given the high frequency of diabetes, as well as prostate cancer in the elderly population, we sought to determine whether diabetic patients treated with three-dimensional conformal external-beam radiotherapy (3DCRT) had an increased risk of late gastrointestinal (GI) or genitourinary (GU) complications. METHODS AND MATERIALS: Nine-hundred forty-four prostate cancer patients were treated between April 1989 and October 1996 using 3DCRT. Median patient age was 69 years (range 48-89), median center of prostate dose was 7211 cGy (range 6211-8074) and median follow-up was 36 months (range 2-99). Patients were evaluated every 6 months with digital rectal examinations, serum PSAs and symptom questionnaires. Radiation morbidity was quantified using Radiation Therapy Oncology Group (RTOG) and modified Late Effects Normal Tissue Task Force (LENT) scales. Patients with a preexisting history of either Type I or Type II diabetes mellitus were coded as diabetics. RESULTS: One hundred twenty-one patients had diabetes (13% of total). Rates of acute morbidity did not differ between diabetics and nondiabetics; however, diabetics experienced significantly more late grade 2 GI toxicity (28% vs. 17%, p = 0.011) and late grade 2 GU toxicity (14% vs. 6%, p = 0.001). There was a trend toward increased late grade 3 and 4 GI complications in diabetics, but not for late grade 3 and 4 GU complications; however, the total number of recorded events for these categories was small. Examining the onset of late toxicity, diabetics developed GU complications earlier than nondiabetics (median: 10 months vs. 24 months, p = 0.02). Considering age, dose, rectal blocking, field size, and history of diabetes in a stepwise multivariate regression model for late grade 2 GI toxicity, dose (p = 0.0001), diabetes (p = 0.0110), and rectal blocking (p = 0.0163) emerged independently predictive for complications. For late grade 2 GU toxicity, only the presence of diabetes remained independently significant (p = 0.0014). CONCLUSION: Diabetes mellitus is common in the elderly prostate cancer population. Diabetics are at a significant risk for the development of late grade 2 GI and GU complications after external-beam radiotherapy for prostate cancer. While diabetes, radiation dose, and rectal blocking predict for late GI complications, only the presence of diabetes influences late GU morbidity. Physicians may consider treatment modifications for diabetic patients, particularly those patients wishing to enter dose-escalation studies. Further study of the relationship between diabetes and late radiation complications is needed.     

Hypofractionated helical tomotherapy using 2.5–2.6 Gy daily fractions for localized prostate cancer

Background

The purpose of this study is to evaluate the tolerability of hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer.

Materials and methods

We evaluated 48 patients with primary adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at 2.6 Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system.

Results

Thirty-two patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy. The median age at diagnosis was 69 years (range 49–87) and the median follow-up 11 months (range 7–40). Grade 2 acute GI toxicity occurred in 9 patients (19 %). No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU toxicities occurred in 19 and 6 % of patients, respectively. The incidence of late grade 2 GI and GU toxicity was 4 and 2 %, respectively. No grade 3 or higher late toxicities were observed. Multivariate analysis showed that patients treated at 2.6 Gy/fraction or those who received a total radiation dose ≥70 Gy had higher rates of grade ≥2 acute GU toxicity (P = 0.004 and P = 0.048, respectively).

Conclusion

Hypofractionated HT in the treatment of localized prostate cancer is well tolerated with no grade 3 or higher early or late GI and GU toxicities. Further research is needed to assess definitive late toxicity and tumor control.     

Thermal therapy of pancreatic tumours using endoluminal ultrasound: Parametric and patient-specific modelling

Purpose: The aim of this study is to investigate endoluminal ultrasound applicator configurations for volumetric thermal ablation and hyperthermia of pancreatic tumours using 3D acoustic and biothermal finite element models. Materials and methods: Parametric studies compared endoluminal heating performance for varying applicator transducer configurations (planar, curvilinear-focused, or radial-diverging), frequencies (1–5 MHz), and anatomical conditions. Patient-specific pancreatic head and body tumour models were used to evaluate feasibility of generating hyperthermia and thermal ablation using an applicator positioned in the duodenal or stomach lumen. Temperature and thermal dose were calculated to define ablation (>?240 EM_43?°C) and moderate hyperthermia (40–45?°C) boundaries, and to assess sparing of sensitive tissues. Proportional-integral control was incorporated to regulate maximum temperature to 70–80?°C for ablation and 45?°C for hyperthermia in target regions.

Results: Parametric studies indicated that 1–3 MHz planar transducers are the most suitable for volumetric ablation, producing 5–8?cm³ lesion volumes for a stationary 5-min sonication. Curvilinear-focused geometries produce more localised ablation to 20–45?mm depth from the GI tract and enhance thermal sparing (T_max?<?42?°C) of the luminal wall. Patient anatomy simulations show feasibility in ablating 60.1–92.9% of head/body tumour volumes (4.3–37.2?cm³) with dose?<?15 EM_43?°C in the luminal wall for 18–48 min treatment durations, using 1–3 applicator placements in GI lumen. For hyperthermia, planar and radial-diverging transducers could maintain up to 8?cm³ and 15?cm³ of tissue, respectively, between 40–45?°C for a single applicator placement. Conclusions: Modelling studies indicate the feasibility of endoluminal ultrasound for volumetric thermal ablation or hyperthermia treatment of pancreatic tumour tissue.     

Prognostic factors for acute toxicity in prostate cancer patients treated with high-dose hypofractionated radiotherapy

Purpose

To prospectively study acute genitourinary (GU) and gastrointestinal (GI) toxicity during hypofractionated radiotherapy.

Patients and materials

One-hundred and seventy-one consecutive men with cT1-T3cN0cM0 prostate cancer were treated at 2.6 Gy/fraction to a total dose of 67.6 for low risk (EQD2 = 79 Gy) and 70.2 Gy for intermediate–high risk (EQD2 = 82 Gy) over 5.2–5.4 weeks (α/β 1.5). Acute toxicity was scored according to RTOG/EORTC toxicity extended criteria after completing a 22-item questionnaire (basal, weekly, at 6 months).

Results

Minimum and median follow-up were 36 and 54.2 months, respectively. GU toxicity grades 0, 1, 2 and 3 were found in 30.4, 37, 32 and 0.6 % of patients, respectively. The figures for grades 0, 1, 2 and 3 GI toxicity were 66, 24, 10 and 0 %. The highest degree of acute reactions was reached at 4–5 weeks. At 6 months, 15 % of patients had GU toxicity (11 % grade 1, 4 % grade 2) and 5.8 % GI toxicity (5.3 % grade 1, 0.5 % grade 2). Multivariate analysis shows that bladder volume receiving ≥65 Gy (V ₆₅) is associated with an increased risk of GU complications (p = 0.017, HR = 1.143, 95 % CI = 1.025–1.276), while history of TURP is linked to lower risk (p = 0.002, HR = 0.310, 95 % CI 0.004–0.370). Mean rectal dose (p = 0.013, HR = 1.089, 95 % CI 1.018–1.116) and total dose (p = 0.019, HR = 0.734, 95 % CI 0.567–0.950) are significantly related to GI toxicity.

Conclusions

This 5-week dose-escalation hypofractionated radiotherapy schedule that uses 3D-conformal radiotherapy without IGRT has resulted in <1 % grade 3 acute complications. Our study suggests that reducing the mean rectal dose and the bladder V ₆₅ helps prevent acute toxicity. TURP before radiotherapy was associated with lower acute GU toxicity.     

Phase 1/2 study of hypofractionated intensity-modulated radiation therapy for prostate cancer including simultaneously integrated boost

Purpose

This study evaluates the safety and efficacy of moderately hypofractionated radiation therapy (RT) with simultaneous integrated boost (HSIB) intensity modulated RT (IMRT) that includes coverage of the seminal vesicles (SVs) and pelvic lymph nodes (LNs).

Clinical hyperthermia of prostate cancer using magnetic nanoparticles: Presentation of a new interstitial technique

The aim of this pilot study was to evaluate whether the technique of magnetic fluid hyperthermia can be used for minimally invasive treatment of prostate cancer. This paper presents the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated while rectum and urethra were spared. Nanoparticle suspensions were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans, using an alternating current magnetic field with a frequency of 100?kHz and variable field strength (0–18?kA?m^?1). Invasive thermometry of the prostate was carried out in the first and last of six weekly hyperthermia sessions of 60?min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive estimation of temperature values in the prostate, based on intra-tumoural distribution of magnetic nanoparticles, can be performed and correlated with invasively measured intra-prostatic temperatures. Using a specially designed cooling device, treatment was well tolerated without anaesthesia. In the first patient treated, maximum and minimum intra-prostatic temperatures measured at a field strength of 4.0–5.0?kA?m^?1 were 48.5°C and 40.0°C during the 1st treatment and 42.5°C and 39.4°C during the 6th treatment, respectively. These first clinical experiences prompted us to initiate a phase I study to evaluate feasibility, toxicity and quality of life during hyperthermia using magnetic nanoparticles in patients with biopsy-proven local recurrence of prostate cancer following radiotherapy with curative intent. To the authors’ knowledge, this is the first report on clinical application of interstitial hyperthermia using magnetic nanoparticles in the treatment of human cancer.     

Pilot study of conformal intensity modulated radiation therapy for localized prostate cancer]

PURPOSE:- To report our experience on treatment planning and acute toxicity in 16 patients suffering from clinically localized prostate cancer treated with high-dose intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: - Between March 2001 and October 2002, 16 patients with clinically localized prostate cancer were treated with IMRT. Treatment planning included an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. All patients received the entire treatment course with IMRT to a prescribed dose of 78 Gy. All IMRT treatment plans were compared with a theoretical conventional three-dimensional conformal radiation therapy (3D-CRT). Acute lower gastro-intestinal (GI) and genito-urinary (GU) toxicity was evaluated in all patients and graded according to the Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE v. 3.0). A relationship between dose volume and clinical toxicity was evaluated. RESULTS: - Ninety-five percent of the PTV2 received more than 76 Gy using IMRT or 3D-CRT with no difference between both methods. The dose-volume histogram mean obtained for the PTV2 was not different between IMRT and 3D-CRT. IMRT improved homogeneity of the delivered dose to the PTV2 as compared with 3D-CRT (7.5 vs 9%, respectively). Ninety-five percent of the PTV1 received 5 Gy more using IMRT with protection of the bladder and the rectum walls. The benefit was considered below 75 and 70 Gy for the wall of the bladder and the rectum, respectively. Grade 2 GI and GU toxicity was observed in four (25%) and five (31%) patients, respectively. No grade 3 toxicity was observed. There was a trend towards a relationship between the mean rectal dose and acute rectal toxicity but without statistical significant difference (P =0.09). CONCLUSION: - Dose escalation with IMRT is feasible with no grade 3 or higher acute GI or GU toxicity. Examination of a larger cohort and longer-term follow-up are warranted in the future.     

Radiation therapy,cisplatin and hyperthermia in combination in management of patients with recurrent carcinomas of the head and neck with metastatic cervical lymph nodes

Twenty-one patients with recurrent carcinomas of the head and neck with metastatic cervical lymph nodes were treated with radiation therapy, cisplatin and hyperthermia in combination, in an attempt to investigate any potential contribution in terms of safety, response, duration of palliation and quality of life. Patients not initially treated with radiation therapy were treated with a median dose of 70Gy and patients initially treated with radiation therapy with a median dose of 30Gy. The median number of weekly cisplatin courses was five and the median number of twice weekly local external ultrasound hyperthermia sessions was five. Average T₉₀, Average T₅₀ and Average T₁₀ were 39.9±1.2°C, 42.4±1.3°C and 44.5±0.8°C, respectively, and Average CEM 43°C T₉₀, Average CEM 43°C T₅₀ and Average CEM 43°C T₁₀ were 7.8±9.6min, 22.6*plusmn;18.8 min and 39.3±25.1 min, respectively. Mean follow-up was 1 year. Nodal complete response was achieved in eight patients and palliation of presenting symptoms in 19. Overall survival was 39% at 1 year. Grade 3 acute skin toxicity was observed in one patient and Grade 3 acute haematological toxicity in one. Radiation therapy, cisplatin and hyperthermia in combination appear to be safe and might improve response, prolong duration of palliation and reinstate quality of life in patients with recurrent carcinomas of the head and neck with metastatic cervical lymph nodes.     

Volume and hormonal effects for acute side effects of rectum and bladder during conformal radiotherapy for prostate cancer

PURPOSE: To identify dosimetric variables predictive of acute gastrointestinal (GI) and genitourinary (GU) toxicity and to determine whether hormonal therapy (HT) is independently associated with acute GI and GU toxicity in prostate cancer patients treated with conformal radiotherapy (RT). METHODS AND MATERIALS: This analysis was performed on 336 patients participating in a multicenter (four hospitals) randomized trial comparing 68 Gy and 78 Gy. The clinical target volume consisted of the prostate with or without the seminal vesicles, depending on the risk of seminal vesicle involvement. The margin from the clinical target volume to the planning target volume was 1 cm. For these patients, the treatment plan for a total dose of 68 Gy was used, because nearly all toxicity appeared before the onset of the 10-Gy boost. Acute toxicity (<120 days) was scored according to the Radiation Therapy Oncology Group criteria. The dosimetric parameters were obtained from the relative and absolute dose-volume/surface histograms derived from the rectal wall (rectal wall volume receiving > or =5-65 Gy) and the bladder surface (bladder surface receiving > or =5-65 Gy). Additionally, relative and absolute dose-length histograms of the rectum were created, and the lengths of rectum receiving more than a certain dose over the whole circumference (rectal length receiving > or =5-65 Gy) were computed. The clinical variables taken into account for GI toxicity were neoadjuvant HT, hospital, and dose-volume group; for GU toxicity, the variables pretreatment GU symptoms, neoadjuvant HT, and transurethral resection of the prostate were analyzed. The variable neoadjuvant HT was divided into three categories: no HT, short-term neoadjuvant HT (started < or =3 months before RT), and long-term neoadjuvant HT (started >3 months before RT). RESULTS: Acute GI toxicity Grade 2 or worse was seen in 46% of the patients. Patients with long-term neoadjuvant HT experienced less Grade 2 or worse toxicity (27%) compared with those receiving short-term neoadjuvant HT (50%) and no HT (50%). The volumes of the prostate and seminal vesicles were significantly smaller in both groups receiving neoadjuvant HT compared with those receiving no HT. In multivariate logistic regression analysis, including the two statistically significant clinical variables neoadjuvant HT and hospital, a volume effect was found for the relative, as well as absolute, rectal wall volumes exposed to intermediate and high doses. Of all the length parameters, the relative rectal length irradiated to doses of > or =5 Gy and > or =30 Gy and absolute lengths receiving > or =5-15 and 30 Gy were significant. Acute GU toxicity Grade 2 or worse was reported in 56% of cases. For patients with pretreatment GU symptoms, the rate was 93%. The use of short-term and long-term neoadjuvant HT resulted in more GU toxicity (73% and 71%) compared with no HT (50%). In multivariate analysis, containing the variables pretreatment symptoms and neoadjuvant HT, only the absolute dose-surface histogram parameters (absolute surface irradiated to > or =40, 45, and 65 Gy) were significantly associated with acute GU toxicity. CONCLUSION: A volume effect was found for acute GI toxicity for relative, as well as absolute, volumes. With regard to acute GU toxicity, an area effect was found, but only for absolute dose-surface histogram parameters. Neoadjuvant HT appeared to be an independent prognostic factor for acute toxicity, resulting in less acute GI toxicity, but more acute GU toxicity. The presence of pretreatment GU symptoms was the most important prognostic factor for GU symptoms during RT.     

Acute and late complications after radiotherapy for prostate cancer: results of a multicenter randomized trial comparing 68 Gy to 78 Gy

PURPOSE: To compare acute and late gastrointestinal (GI) and genitourinary (GU) side effects in prostate cancer patients randomized to receive 68 Gy or 78 Gy. METHODS AND MATERIALS: Between June 1997 and February 2003, 669 prostate cancer patients were randomized between radiotherapy with a dose of 68 Gy and 78 Gy, in 2 Gy per fraction and using three-dimensional conformal radiotherapy. All T stages with prostate-specific antigen (PSA) <60 ng/mL were included, except any T1a and well-differentiated T1b-c tumors with PSA < or =4 ng/mL. Stratification was done for four dose-volume groups (according to the risk of seminal vesicles [SV] involvement), age, hormonal treatment (HT), and hospital. The clinical target volume (CTV) consisted of the prostate with or without the SV, depending on the estimated risk of SV invasion. The CTV-planning target volume (PTV) margin was 1 cm for the first 68 Gy and was reduced to 0.5 cm (0 cm toward the rectum) for the last 10 Gy in the 78 Gy arm. Four Dutch hospitals participated in this Phase III trial. Evaluation of acute and late toxicity was based on 658 and 643 patients, respectively. For acute toxicity (<120 days), the Radiation Therapy Oncology Group (RTOG) scoring system was used and the maximum score was reported. Late toxicity (>120 days) was scored according to the slightly adapted RTOG/European Organization for Research and Treatment of Cancer (EORTC) criteria. RESULTS: The median follow-up time was 31 months. For acute toxicity no significant differences were seen between the two randomization arms. GI toxicity Grade 2 and 3 was reported as the maximum acute toxicity in 44% and 5% of the patients, respectively. For acute GU toxicity, these figures were 41% and 13%. No significant differences between both randomization arms were seen for late GI and GU toxicity, except for rectal bleeding requiring laser treatment or transfusion (p = 0.007) and nocturia (p = 0.05). The 3-year cumulative risk of late RTOG/EORTC GI toxicity grade > or =2 was 23.2% for 68 Gy, and 26.5% for 78 Gy (p = 0.3). The 3-year risks of late RTOG/EORTC GU toxicity grade > or =2 were 28.5% and 30.2% for 68 Gy and 78 Gy, respectively (p = 0.3). Factors related to acute GI toxicity were HT (p < 0.001), a higher dose-volume group (p = 0.01), and pretreatment GI symptoms (p = 0.04). For acute GU toxicity, prognostic factors were: pretreatment GU symptoms (p < 0.001), HT (p = 0.003), and prior transurethral resection of the prostate (TURP) (p = 0.02). A history of abdominal surgery (p < 0.001) and pretreatment GI symptoms (p = 0.001) were associated with a higher incidence of late GI grade > or =2 toxicity, whereas HT (p < 0.001), pretreatment GU symptoms (p < 0.001), and prior TURP (p = 0.006) were prognostic factors for late GU grade > or =2. CONCLUSIONS: Raising the dose to the prostate from 68 Gy to 78 Gy resulted in higher incidences of acute and late GI and GU toxicity, but these differences were not significant, except for late rectal bleeding requiring treatment and late nocturia. Other factors than the studied dose levels appeared to be important in predicting toxicity after radiotherapy, especially previous surgical interventions (abdominal surgery or TURP), hormonal therapy, and the presence of pretreatment symptoms.     

Estimation of the Incidence of Late Bladder and Rectum Complications After High-Dose (70–78 Gy) Conformal Radiotherapy for Prostate Cancer,Using Dose–Volume Histograms

Purpose: To investigate whether Dose–Volume Histogram (DVH) parameters can be used to identify risk groups for developing late gastrointestinal (GI) and genitourinary (GU) complications after conformal radiotherapy for prostate cancer.Methods and Materials: DVH parameters were analyzed for 130 patients with localized prostate cancer, treated with conformal radiotherapy in a dose-escalating protocol (70–78 Gy, 2 Gy per fraction). The incidence of late (>6 months) GI and GU complications was classified using the RTOG/EORTC and the SOMA/LENT scoring system. In addition, GI complications were divided in nonsevere and severe (requiring one or more laser treatments or blood transfusions) rectal bleeding. The median follow-up time was 24 months. We investigated whether rectal and bladder wall volumes, irradiated to various dose levels, correlated with the observed actuarial incidences of GI and GU complications, using volume as a continuous variable. Subsequently, for each dose level in the DVH, the rectal wall volumes were dichotomized using different volumes as cutoff levels. The impact of the total radiation dose, and the maximum radiation dose in the rectal and bladder wall was analyzed as well.Results: The actuarial incidence at 2 years for GI complications ≥Grade II was 14% (RTOG/EORTC) or 20% (SOMA/LENT); for GU complications ≥Grade III 8% (RTOG/EORTC) or 21% (SOMA/LENT). Neither for GI complications ≥Grade II (RTOG/EORTC or SOMA/LENT), nor for GU complications ≥Grade III (RTOG/EORTC or SOMA/LENT), was a significant correlation found between any of the DVH parameters and the actuarial incidence of complications. For severe rectal bleeding (actuarial incidence at 2 years 3%), four consecutive volume cutoff levels were found, which significantly discriminated between high and low risk. A trend was observed that a total radiation dose ≥ 74 Gy (or a maximum radiation dose in the rectal wall >75 Gy) resulted in a higher incidence of severe rectal bleeding (p = 0.07).Conclusions: These data show that dose escalation up to 78 Gy, using a conformal technique, is feasible. However, these data have also demonstrated that the incidence of severe late rectal bleeding is increased above certain dose–volume thresholds.     

Incidence and clinical course of hemorrhagic radiation proctitis after iodine-125 prostate brachytherapy

PURPOSE: Hemorrhagic radiation proctitis (HRP) is a potential complication of prostate brachytherapy. We sought to determine the incidence and clinical course of hemorrhagic radiation proctitis after iodine-125 (125I) prostate brachytherapy. PATIENTS AND METHODS: Between 1995 and 2003, 221 consecutive patients were treated at the Barrett Cancer Center with permanent 125I seed implantation for presumed localized adenocarcinoma of the prostate. No patients received EBRT. All cases of HRP were confirmed by colonoscopy. Median follow-up was 52 months. All patients were evaluated for HRP using a 5-grade rectal bleeding scale developed by the Radiation Therapeutic Oncology Group. RESULTS: Thirty-three patients experienced grade>or=1 toxicity at some point after treatment. Twenty patients developed grade 2 toxicity, 9 developed grade 3, and 2 developed grade 4. The median time to onset of symptoms of HRP was 14 months. The incidence of HRP had a bimodal temporal onset, with a peak seen at 4 months and a second larger peak at 16 months. Peak toxicity occurred at 18 months after the onset of rectal bleeding, after which there was a sharp decline in toxicity. CONCLUSION: This study demonstrates tolerable rectal morbidity after transperineal prostate brachytherapy of the prostate. Hemorrhagic radiation proctitis occurring after brachytherapy for prostate cancer is usually self-limiting and frequently resolves without treatment or with minor medical treatment. Patients develop HRP soon after treatment or after a delay in treatment. Symptoms appear to peak 18 months after the onset of HRP.     

局限期前列腺癌大分割调强放疗临床Ⅱ期研究

目的 观察前列腺癌2.7 Gy 25次大分割调强适形放疗的疗效和不良反应。