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

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

Epidermoid carcinomas of the anal canal treated with definitive radiation therapy in a series of 305 patients]

PURPOSE: To identify prognostic factors and treatment toxicity in a serie of epidermoid cancers of the anal canal without evident metastasis. PATIENTS AND METHODS: Between June 1972 and January 1997, 305 patients (pts) were treated with curative-intent radiation therapy (RT). The T-stages according to the 1987 UICC classification were: 26 T1, 141 T2, 104 T3, and 34 T4. There were 49 pts with nodal involvement at presentation. Pretreatment anal function scoring according to our in-house system was: 22 scored 0, 182 scored 1, 74 scored 2, 7 scored 3, 11 scored 4, and 9 not available pts. The treatment started with external beam RT (EBRT) in 303 pts (median dose: 45 Gy). After a rest period of 4 to 6 weeks, a boost of 20 Gy was delivered by EBRT in 279 pts and by interstitial 192Ir brachytherapy (Bcy) in 17 pts. Seven pts received only one course of EBRT (mean dose: 49.5 Gy) and 2 pts were treated with interstitial 192Ir Bcy alone (55 and 60 Gy, respectively). Concomitant chemotherapy (5-fluoro-uracil and either mitomycin C or cisplatin) was delivered to 19 pts. Mean follow-up was 103 months. RESULTS: At the end of RT local tumor clinical complete response (cCR) rate was 80%. Out of 61 non responders or local progressive tumors 27 (44%) were salvaged with abdominoperineal resection (APR). The rate of local tumor relapse (LR) was 12%. Out of 37 LTR, 20 (54%) were salvaged with APR and one with interstitial 192Ir Bcy. The orevall local tumor control (LC) rate with or without salvage local treatment was 84%. LC rate with a good anal function scoring (score 0 and 1) was 56.5%. Among 181/186 available pts who preserved their anus, 94% had a good anal function scoring. For a subgroup of 15 pts with length tumor <2 cm-N0, the LC rate after the end of RT was 100%, the LC rate with or without local salvage treatment was 100%, and among 13 available pts who preserved their anus, the anal function scoring was good in 12 pts (92%). The 10-years disease-free survival was 74%. After multivariate analysis, 3 independent predicting factors significantly influenced the disease-free survival: gap duration between 2 courses of RT (>38 days vs < or =38 days, P =0.0025), pretreatment anal function scoring (0 vs 1 vs 2 vs 3 vs 4, P =4.4 10(-6)), and cCR after the end of RT (no complete response vs complete response, P =2.5 10(-14)). CONCLUSION: We confirm excellent results with RT in T1 and T2 lesions. However, chemoradiotherapy should be prefered to improve survival free of colostomy with a good anal sphincter function for tumors more than or equal to 2 cm in length and locally advanced tumors.     

Regional hyperthermia for advanced tumors: a clinical study of 353 patients

A Phase I study using deep regional hyperthermia (HT) with an annular phased array was conducted in 14 U.S. medical centers from 1980 through 1986. There were 353 patients whose average age was 57 years. All patients had advanced recurrent or persistent tumors. Prior frequently complex, multimodality anti-cancer therapy was received by 71% of the patients. Gastrointestinal adenocarcinoma was present in 146 (41%) patients, genitourinary tumors in 86 (24%), soft tissue sarcomas in 46 (13%), malignant melanoma in 21 (6%) and 15% had other tumors. The sites treated included: pelvis 55%, abdomen 21%, liver 14%, thorax 6%, and other sites 3%. All patients received deep regional HT with an average frequency of 55 MHz. A total of 1412 HT treatments was administered to these 353 patients with an aim to increase the temperature in the volume of interest to greater than 42 degrees C for greater than or equal to 30 minutes. Thermal dose (TD in equivalent minutes at 42.5 degrees C) was less than 50 in 104 (29%), greater than or equal to 50 less than 100 in 30 (11%), greater than or equal to 100 in 26 (7%), and greater than 200 in 34 (10%). The remaining 150 (42%) patients had TD = 0. In addition to HT, 260 (74%) received radiotherapy (RT). RT was given at 180 or 200 cGy daily with an average total dose of 33.4 Gy. A total of 42 (12%) patients were given chemotherapy (CT) with HT, and 15 (4%) CT + HT + RT/HT alone was given to 47 (13%) patients. Complete response (CR) was obtained in 35 (10%) and partial response (PR) in 59 (17%) patients. CR was 12% in patients who received RT, vs 2% in those who did not receive it, p = 0.003. Radiation dose was an important factor influencing response, p less than 0.001. Thermal dose was not an important parameter influencing tumor response. A duration of CR ranged from 4 to 73 weeks with an average duration of 31 weeks and the median duration of 28 weeks. The overall 2-year survival was 13% with the median survival of 42 weeks. Patients with CR and PR had a 2 year survival of 41%, and a median survival of 71 weeks. This compared with 8% 2-year survival and 24 weeks median survival in patients who did not have CR or PR, p less than 0.001. Of the patients presenting with significant pain, 62% had complete or partial pain relief.(ABSTRACT TRUNCATED AT 400 WORDS)     

Interstitial thermoradiotherapy for recurrent or persistent tumours

Between 1984 and 1986, 31 sites in 27 patients with biopsy proven tumours were treated with a combination of interstitial microwave hyperthermia (HT) and iridium 192 implants (RT). The 31 sites treated included fifteen (48 per cent) head and neck, six (20 per cent) breast, four (13 per cent) vagina and cervix, and six (20 per cent) others. All patients had prior surgery, RT, or chemotherapy. Of the 31 sites treated, 19 (61 per cent) had complete response (CR) with no recurrence in the volume treated. Additionally, eight patients remained free of tumour from 3 to 24 months. Partial response (PR) was seen in 11 (36 per cent) sites while one (3 per cent) had lesser degree tumour regression. Tumour control rate correlated well with the dose of radiation, p = 0.02, and tumour volume, p = 0.02, but not with thermal dose. Treatment complications of significance occurred in one (3 per cent) site, which developed soft tissue necrosis. This study again has demonstrated the effectiveness of RT-HT combination in treatment of recurrent tumours.     

Deep regional hyperthermia of the liver. A clinical study of 49 patients

From 1981 to 1986, six medical centers participated in feasibility studies of radiofrequency deep regional hyperthermia (HT) in the treatment of hepatic metastases. A total of 49 patients, 32 men and 17 women, were treated with an annular phased array. Colon was the primary site in 74% of the patients, and adenocarcinoma was the diagnosis in 80%. More than one half of the patients had been treated previously. This included chemotherapy (CT) in 17 patients and radiotherapy (RT) in 10 patients, with a mean RT dose of 24 Gy. Upper abdominal pain was the dominant presenting symptom in 53% of patients. In the study, treatment was administered as follows: 14 (28%) patients received HT alone, 17 (35%) received HT + RT, 14 (28%) received HT + CT, and 4 (8%) received HT + RT + CT. A total of 157 HT treatments was administered at a mean frequency of 55 MHz and a mean power of 780 watts. The number of HT sessions ranged from 1 to 8, with a mean of 3.2 treatments per patient. Temperature was monitored continuously throughout each treatment session. The treatment aim was to reach and maintain a temperature of 42.5 degrees C for 30 min. In practice, owing to the difficulty in reaching this temperature, an equivalent (lower) temperature from 40 to 42 degrees C was used, extending the duration of treatment sessions to 45-60 min. Thermal dose was defined as the number of minutes at 42.5 degrees C or its equivalent. In 21 (43%) patients, a temperature less than 40 degrees C was obtained and thermal dose = 0. Thermal dose was less than or equal to 50 in 17 (35%) patients, greater than 50 less than or equal to 100 in 7 (14%), and greater than 100 in 4 (8%). RT was given at a daily dose of 1.8 Gy to a total of less than 20 Gy in 14 patients, greater than 20 less than or equal to 30 Gy in 6, and greater than 30 Gy in 1. CT consisted of 5-Fluorouracil by way of Hepatic Artery Infusion (HAI) in 9 patients, i.v. cisplatin in 5, and doxorubicin HAI in 3. Objective tumor regression (CR + PR) was seen in 6 (12%) patients. An additional 10 (20%) patients had less than 50% greater than 25% tumor regression, and 10 (20%) had complete or partial pain relief. The median duration of CR and PR was 26 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)     

Long-term outcomes after external beam irradiation and brachytherapy boost for base-of-tongue cancers

PURPOSE: To assess long-term efficacy and toxicity associated with external beam irradiation (EBRT) and interstitial (192)Ir implantation for the treatment of squamous carcinoma of the base of tongue. METHODS AND MATERIALS: Between April 1975 and December 1993, 41 patients with base-of-tongue carcinomas were treated with (192)Ir interstitial implants after EBRT at Stanford University. One patient had Stage I, 6 had Stage II, 7 had Stage III, and 27 had Stage IV tumors. Twenty-eight patients had cervical lymph node involvement at diagnosis. All received EBRT to a median dose of 50 Gy (range 48.9-68 Gy) to the primary tumor and regional lymph nodes before brachytherapy. Interstitial implant was performed 2-4 weeks after EBRT. Intraoperatively, nylon catheters were placed via steel trocars into the base of tongue, glossotonsillar groove, and pharyngo-epiglottic fold using a catheter looping technique. Twenty-three of 28 node-positive patients also underwent simultaneous neck dissections. Postoperatively, the (192)Ir seeds were inserted and allowed to remain in place for approximately 35 h to achieve a median tumor dose of 26 Gy (range 20-34 Gy) to a median volume of 73 cc. Survival, local control, and complications were assessed. RESULTS: With a median follow-up of 62 months (range 9-215) for all patients and 90 months for alive patients, the 5-year Kaplan-Meier survival estimate was 66%. The 5-year local control rate was 82%, with 7 patients recurring locally, 2 of whom were salvaged with surgery. Nodal control was achieved in 93% of patients with either EBRT alone or in combination with neck dissection. The 5-year freedom from distant metastasis rate was 83%. Acute complications included transient bleeding (5%) and infection (8%). Late complication included soft-tissue necrosis/ulceration (7%), osteoradionecrosis (5%), and xerostomia. CONCLUSION: Base-of-tongue carcinoma can be effectively treated with EBRT and (192)Ir implant boost. Local control is excellent and complication rates are acceptable.     

Quality assurance problems in clinical hyperthermia and their impact on therapeutic outcome: a Report by the Radiation Therapy Oncology Group

Since February 1981, 300 patients with superficial measurable tumors were randomized on an RTOG protocol (81-04) involving fractionated radiation therapy (4.00 Gy twice weekly for a total of 32.00 Gy), either alone or followed immediately by hyperthermia (42.5 degrees C, 60 min). This is a report of 218 eligible patients with single lesions: 107 treated with radiotherapy alone (RT), 111 with radiotherapy plus hyperthermia (RT + HT). Only 56% of the 24 tumors less than 3 cm and 36% of the 53 lesions larger than 3 cm received what was felt to be "adequate" therapy (greater than or equal to 29 Gy and 8 heating sessions). Overall complete response (CR) was observed in 28% of the patients treated with RT, and 32% of the patients receiving RT and heat. Response has been found in previous analyses of this and other RTOG studies to be significantly related to both maximum tumor diameter (less than 3 or greater than or equal to 3 cm) and site/histology (breast/adenocarcinoma, head and neck/squamous, or other site/histologies). In the head and neck tumors less than 3 cm in diameter there was no difference in CR with irradiation alone or combined with hyperthermia (46% vs 43%). However, in the breast, and trunk and extremities a better CR rate was noted with irradiation and heat (55% and 67%) than with irradiation alone (33% and 0). In lesions less than 3 cm treated with irradiation and heat the probability of remaining in response was 80% compared with 15% with irradiation alone. In lesions larger than 3 cm no difference in CR was observed in either treatment group. It has been hypothesized that the response rate is higher in patients with smaller lesions (less than 3 cm) and in breast/chest wall, trunk/extremity lesions because these tumors and anatomical sites are easier to heat adequately. Problems encountered in correlating tumor response with quality of heating include less than optimal heating in larger lesions and the limited ability of current thermometry to accurately represent the temperature distribution in a tumor. Furthermore, differences in equipment and treatment practices among institutions add to the variability in heat administration data collected. In addition, tumor response may be difficult to judge because of short survival of some patients and occasionally rapid tumor regression that may cause necrosis which may be misinterpreted as persistent tumor.(ABSTRACT TRUNCATED AT 400 WORDS)     

高剂量率192铱后装机腔内加外照射治疗宫颈癌60例临床分析

目的:探讨高剂量率192铱后装腔内加体外照射治疗宫颈癌的疗效及副作用等。方法:2005年3月至2007年1月本院放疗中心共60例宫颈癌患者,采用8MV-X线直线加速器全盆照射,开始体外全盆腔照射,5次/周,2Gy/次,剂量25-40Gy;然后中间挡铅,4个野照射,5次/周,2Gy/次,宫旁剂量20-25Gy:同时腔内治疗,1次/周,6Gy/次,剂量为35-40Gy。腔内治疗采用ZL-HDR18铱高剂量率后装治疗机,全部病例均宫颈阴道同时进行。腔内治疗每周1次,A点剂量36-40GY/6-7F/6-7w,腔内治疗当日停体外照射,治疗时间56-77天。结果:CR+PR 100%,随访超过3年,随访率达95%,3年生存率Ⅱ期88.3%,Ⅲ期82.9%;早期放射性直肠反应发生率为12.4%,膀胱反应发生率5.2%;晚期放射性直肠炎发生率13.8%,膀胱炎3.8%。结论:高剂量率192铱后装机腔内加体外治疗宫颈癌的疗效满意,患者生存率较高,耐受好,并发症少。     

Long‐term outcome in localized extranodal mucosa‐associated lymphoid tissue lymphomas treated with radiotherapy

BACKGROUND:

This study was conducted to evaluate the long‐term outcomes in patients with stage IE and IIE mucosa‐associated lymphoid tissue (MALT) lymphomas treated with involved field radiotherapy (RT).

METHODS:

Between 1989 and 2004, 192 patients with stage I and II MALT lymphomas were treated. The report focuses on 167 patients who received RT. The median age of patients was 58 years with a female predominance (2:1). Presenting sites were as follows: orbital adnexa in 71 patients, salivary glands in 28 patients, stomach in 25 patients, thyroid in 21 patients, and other sites in 22 patients. The median dose to nonorbital sites was 30 grays (Gy) (range, 17.5‐35 Gy) and was 25 Gy for the orbit (range, 25‐35 Gy). The median follow‐up was 7.4 years (range, 0.67‐16.20 years).

RESULTS:

Complete response and complete response, unconfirmed (CR/CRu) was noted in 166 (99%) patients. The 10‐year recurrence‐free rate (RFR) was 76%, the disease‐free survival (DFS) rate was 68%, the overall survival (OS) rate was 87%, and the cause‐specific survival rate was 98%. According to presenting site, the 10‐year RFR was 95% for thyroid, 92% for stomach, 68% for salivary glands, and 67% for orbit. Patients with thyroid and gastric MALTs had better outcome compared with patients with MALTs diagnosed at other sites (P = .004). Among those patients who achieved CR, 19% developed disease recurrence (n = 31), chiefly in distant sites or untreated contralateral‐paired organs. At the time of disease recurrence, 7 patients (23%) had transformed to diffuse large B‐cell lymphoma, 2 of whom died of lymphoma. The 5‐year OS rate after treatment failure was 83%.

CONCLUSIONS:

Patients with localized MALT lymphomas are reported to have excellent clinical outcome after moderate‐dose RT, and some are likely cured. In the current study, thyroid and gastric MALTs were found to have significantly less risk of distant recurrence. Despite disease recurrence, the overall survival remains excellent in these patients. Cancer 2010. © 2010 American Cancer Society.     

Interstitial irradiation by 192Ir seed assemblies in fixed cervical lymph node metastases

Eleven patients with fixed cervical lymph node metastases were treated using external irradiation followed by interstitial implants, 137Cs needles were used for one patient and 192Ir seed-assemblies for 10 patients. The local tumor responses were 4 CR, 6 PR and 1 NC. Acute tolerance was good, and there were no major late injuries except for one case of severe subcutaneous fibrosis. No morbidities such as local infection, bleeding or pulmonary injuries were encountered. Clear-cut dose control relationships were demonstrated; the local control of the nodes treated with intervals of more than one month between external and interstitial irradiation was poor. It is considered that adequate treatment is to give 40 Gy over 4 weeks by external irradiation first, then, after an interval of 2 weeks, to give 40-50 Gy over 4-5 days using 192Ir interstitial implants. The interstitial implants appeared to provide an improvement in local control and in the therapeutic ratio of fixed cervical lymph node metastases.     

Brachytherapy with Ir as treatment of carcinoma of the tarsal structure of the eyelid

PURPOSE: Some eyelid tumors present a great challenge for surgical therapy because of the cosmetic and functional impairment. Interstitial radiation with (192)Ir is an optimal alternative treatment modality. The aim of this study was to evaluate the local tumor control and cosmetic results in patients with eyelid tumors treated by interstitial (192)Ir wires. METHODS AND MATERIALS: Twenty-four previously untreated carcinomas involving the eyelid tarsal structure in 23 patients were treated with (192)Ir wire implantation. The tumor location was in the lower eyelid in 22 cases and in the upper eyelid in 2. The mean tumor size was 1.33 cm. Of the 24 tumors, 79.2% were basal cell carcinoma, 16.7% were squamous cell carcinoma, and 4.2% were adenocarcinoma. The total radiation dose was 4000 cGy, delivered to 2-mm depth (mean dose rate, 73 cGy/h). RESULTS: The mean follow-up was 43 months. Local control was obtained in 22 (91.6%) of 24 tumors. Good functional results were achieved in all patients. CONCLUSION: (192)Ir interstitial brachytherapy in a braided silk filament appears to be an excellent method to treat carcinomas involving the eyelid tarsal structure for tumor control and functional and cosmetic results.     

鼻咽癌后程X刀分次推量放疗的疗效观察

 目的 探讨鼻咽癌的放射治疗疗效。方法 将1996年至2000年常规放疗及后程X刀分次推量放疗的患者，按入组条件分为二组，分组进行肿瘤区有效生物剂量估计，低剂量区剂量估计，正常组织（口腔黏膜、唾液腺）剂量估计，近期疗效评价及1，3，5年生存率。结果 两组肿瘤区放射治疗有效生物剂量估计分别为83.23 Gy，99.09 Gy；两组咽旁间隙、茎突、颈动、静脉区低剂量区放射剂量估计分别为54.96 Gy，76.8 Gy；正常组织（口腔黏膜、唾液腺）剂量估计为66.24 Gy，53.76 Gy；两组完全缓解（CR）率、部分缓解（PR）率分别88.4 %，100 %及96.4 %，100 %；两组1，3，5年生存率分别为92.8 %，71.4 %，53.5 %；96.2 %，84.6 %，76.6 %。结论 后程X刀分次推量放疗提高了鼻咽癌常规放疗肿瘤区及低剂量区的放疗剂量，降低了正常组织的损伤剂量，是提高近期疗效及1，3，5年生存率的主要因素。临床放疗应严格筛选适应证，选择侵犯咽旁间隙、茎突、颈动、静脉区的病例为主。     

Exclusive low-dose-rate brachytherapy in 279 patients with T2N0 mobile tongue carcinoma

PURPOSE: To evaluate the therapeutic results obtained with (192)Ir low-dose-rate interstitial brachytherapy in T2N0 mobile tongue carcinoma. PATIENTS AND METHODS: Between December 1979 and January 1998, 279 patients with T2N0 mobile tongue carcinoma were treated by exclusive low-dose-rate brachytherapy, with or without neck dissection. (192)Ir brachytherapy was performed according to the "Paris system" with a median total dose of 60 Gy (median dose rate, 0.5 Gy/h). RESULTS: Overall survival was 74.3% and 46.6% at 2 and 5 years. Local control was 79.1% at 2 years and regional control, respectively, 75.9% and 69.5% at 2 and 5 years (Kaplan-Meier method). Systematic dissection revealed 44.6% occult node metastases, and histologic lymph node involvement was identified as the main significant factor for survival. Complication rate was 16.5% (Grade 3, 2.9%). Half of the patients presented previous and/or successive malignant tumor (ear-nose-throat, esophagus, or bronchus). CONCLUSION: Exclusive low-dose-rate brachytherapy is an effective treatment for T2 tongue carcinoma. Regional control and survival are excellent in patients undergoing systematic neck dissection, which is mandatory in our experience because of a high rate of occult lymph node metastases.     

Interstitial thermoradiotherapy: thermal dosimetry and clinical results

From August 1977 to August 1986, 72 patients with advanced primary or recurrent cancers were treated using interstitial thermoradiotherapy. Sites treated included the pelvis in 49 patients, the head and neck in 15, and other sites in six. Median tumor volume was 52 cm3, and all but nine patients had received prior irradiation. In 69 patients, hollow stainless steel catheters were implanted and used as electrodes with a 0.5 MHz radiofrequency (RF) generator, whereas in three patients, standard plastic Henschke tubes were used with a commercially available interstitial microwave (MW) system operating at 915 MHz. Most patients were heated intraoperatively for 30 minutes, aiming for a minimum measured intratumoral temperature (Tmin) of 42 degrees C. The implant was occasionally preceded by external irradiation, and after hyperthermia, the catheters were afterloaded with 192Ir for brachytherapy. Tmin exceeded 42 degrees, 42.5 degrees, 43 degrees, and 44 degrees in 25, 16, 12, and 3, respectively, of 70 patients with temperature data available, and the probability of successful heating was independent of tumor volume or site. Twenty-five of 69 (36%) evaluable patients achieved a complete response (CR). Probability of CR demonstrated a significant univariate dependence upon Tmin, radiation dose, site treated, and tumor volume, but multivariate analysis showed only three significant predictor variables: tumor volume, radiation dose, and Tmin. The probability of a CR ranged from 95% for patients with small tumors receiving high doses of radiation and adequate heat, to 5% for patients with large tumors receiving low radiation doses and less than adequate heat. Of 25 patients with CR, 10 relapsed; median response duration was less than 18 months, depended marginally upon disease site, and was independent of Tmin, radiation dose, and tumor volume. Seventeen patients sustained a complication, of which nine were severe enough to require hospitalization or surgery. All severe complications occurred in patients with pelvic tumors. The probability of a complication of any severity had a significant univariate association with maximum intratumoral temperature (Tmax) and tumor size. We conclude that interstitial thermoradiotherapy offers the promise of heating large tumors in locations where externally applied hyperthermia has not been successful.     

Efficacy of irradiation and external hyperthermia in locally advanced, hormone-refractory or radiation recurrent prostate cancer: a preliminary report

PURPOSE: To present a preliminary report on the feasibility, efficacy, and toxicity of irradiation (RT) and hyperthermia (HT) in patients with locally advanced, hormone-refractory prostate cancer (LAHRPC) who may or may not have received prior RT. METHODS AND MATERIALS: Between 1997 and 2002, 13 consecutive patients with LAHRPC or RT-recurrent prostate cancer were treated with RT and HT on a Phase I-II protocol. Eight patients had RT-recurrent LAHRPC (Group A) and 5 had LAHRPC without prior RT (Group B). All patients had large and clinically symptomatic tumors. The median RT dose was 39.6 Gy and 66.6 Gy in Groups A and B, respectively. External deep HT was delivered using a BSD-2000 Sigma-60 applicator. The median number of HT treatments was 8 in group A and 10 in group B. RESULTS: The median follow-up was 14 and 13 months for Groups A and B, respectively. All patients achieved a complete or partial response (CR/PR) and complete palliation of symptoms. Eleven patients had follow-up CT scans that demonstrated a CR in six and a PR in five. Two patients, who died of metastasis, did not have CT scans and had a PR on digital rectal examination. Two patients demonstrated a biochemical CR. The median duration of the CR/PR among Group A patients was 12 months after therapy. Three patients in Group A developed tumor recurrence at 9, 17, and 27 months after repeat RT to doses of 39.6, 36, and 50 Gy, respectively. At last follow-up, no Group B patient developed local recurrence. Grade 1-2 rectal bleeding was noted in 3 patients. RT and HT were generally well tolerated by all patients who had not previously undergone RT. Of the 8 patients who had, 6 (75%) tolerated retreatment well with minimal or no complications. Two patients in the repeat RT group had severe complications. One patient with lymphoma and factor XI deficiency developed Grade 4 hemorrhagic cystitis. Another previously irradiated patient developed a rectovesical fistula 4 months after retreatment, after disappearance of a large, invasive, and necrotic tumor. CONCLUSION: This preliminary report demonstrates the feasibility and efficacy of RT and HT in patients with LAHRPC, who may or may not have received prior RT. Presently, such patients who have undergone previous RT have no effective treatment options. RT and HT were generally well tolerated by patients who were not previously undergone RT. Of those who had been, most (6 of 8) tolerated retreatment well with minimal or no complications. The high-risk factors for treatment- and tumor regression-related side effects include the presence of large necrotic tumors, previous RT with a large dose/fraction, and the presence of bleeding disorders. Despite the size of these large tumors, RT and HT resulted in significant tumor shrinkage, rapid serum prostate-specific antigen decline, durable treatment responses, and durable palliation of symptoms. Additional clinical studies are warranted.     

高剂量率^192铱后装机腔内加外照射治疗宫颈癌60例临床分析

目的：探讨高剂量率^192铱后装腔内加体外照射治疗宫颈癌的疗效及副作用等。方法：2005年3月至2007年1月本院放疗中心共60例宫颈癌患者,采用8MV-X线直线加速器全盆照射,开始体外全盆腔照射,5次/周,2Gy/次,剂量25-40Gy;然后中间挡铅,4个野照射,5次/周,2Gy/次,宫旁剂量20-25Gy：同时腔内治疗,1次/周,6Gy/次,剂量为35-40Gy。腔内治疗采用ZL-HDR18铱高剂量率后装治疗机,全部病例均宫颈阴道同时进行。腔内治疗每周1次,A点剂量36-40GY/6-7F/6-7w,腔内治疗当日停体外照射,治疗时间56-77天。结果：CR＋PR 100%,随访超过3年,随访率达95%,3年生存率Ⅱ期88.3%,Ⅲ期82.9%;早期放射性直肠反应发生率为12.4%,膀胱反应发生率5.2%;晚期放射性直肠炎发生率13.8%,膀胱炎3.8%。结论：高剂量率^192铱后装机腔内加体外治疗宫颈癌的疗效满意,患者生存率较高,耐受好,并发症少。     

Multimodality therapy for CNS mixed malignant germ cell tumors (MMGCT): results of a phase II multi-institutional study

In order to improve outcomes for CNS mixed malignant germ cell tumors (MMGCT) we sought to increase complete responses (CR) to initial therapy, through intensifying neoadjuvant chemotherapy (CHT1) with added ifosfamide, encouraging second-look surgery, and administering dose-intensive, stem cell-supported chemotherapy (CHT2) to patients with residual tumor, all prior to radiation therapy (RT). Diagnosis was confirmed by biopsy or elevated germ cell tumor markers. After tumor staging was completed, patients received four cycles of chemotherapy (cisplatin, etoposide and ifosfamide, “CHT1”). In patients with <CR, second-look surgery was encouraged. Patients with residual tumor received two cycles of high dose, sub-ablative chemotherapy with carboplatin and cyclophosphamide (“CHT2”) with peripheral stem cell support. All patients then received RT: for localized tumors with CR before RT, 36 gray (Gy) whole ventricular radiation therapy (WVRT) plus 50.4 Gy boost to primary; for disseminated tumors or < CR before RT, craniospinal irradiation (CSI) plus boosts to primary site(s) and bulky metastases. 26 patients (19 M0, 7 M+) were enrolled. The diagnosis was established by histology (20) or elevated markers (6). Objective responses to CHT1 were complete in 12/22 patients with evaluable disease and partial in 10; 8 additional tumors were rendered CR prior to RT (5 surgical CRs: 3 initial, 2 second-look; 3 CRs to CHT2). Thus, 20/26 patients (77 %) were free of disease (CR) prior to RT. Six-year relapse-free survival was 63 ± 10 %; overall survival was 68 ± 9 %. Of 16 M0 patients who received only WVRT, four relapsed in the spine, outside the radiation field. The relatively high frequency (25 %) of relapse outside the initial RT volume highlights the limitations of initial staging criteria and the curative potential of conventional and high dose chemotherapy. CSI remains the standard of care for CNS MMGCT, even for patients with localized disease.     

Brachytherapy: Results of two different therapy strategies for patients with primary glioblastoma multiforme

BACKGROUND: In the current study, the authors describe and compare two different strategies of brachytherapy for the treatment of patients with primary glioblastoma multiforme (GBM). METHODS: The study was comprised of 84 patients. Forty-five patients were implanted with permanent or temporary low activity iodine-125 ((125)I) seeds in Cologne and 21 patients were implanted with temporary iridium-192 ((192)Ir) wires in Amsterdam. Both groups received external beam radiation therapy (EBRT); the (125)I group received 10-30 grays (Gy) with the implant in situ and the (192)Ir group received 60 Gy before implantation. In Cologne, implantation was performed after a diagnostic stereotactic biopsy whereas in Amsterdam implantation took place after cytoreductive diagnostic surgery. In addition, 18 patients in Amsterdam served as a control group. This group received only EBRT after cytoreductive surgery. RESULTS: In both groups the mean age of the patients was between 50-55 years, with 80% of the patients age > 45 years. The mean implantation volume encompassed by the referenced isodose was 23 cm(3) for (125)I and 48 cm(3) for (192)Ir. Initial dose rates were 2. 5-2.9 centigrays (cGy)/hour for permanent (125)I, 4.6 cGy/hour for temporary (125)I, and 44-100 cGy/hour (mean, 61 cGy) for (192)Ir. A total dose of 50-60 Gy, 60-80 Gy, and 40 Gy, respectively, was administered at the outer margins of the tumor. The median survival was approximately 16 months for both the (125)I group and the (192)Ir group. This was 6 months longer than the median survival in the control group. Reoperations were performed in 4 patients in the (125)I group (9%) versus 7 patients in the (192)Ir group (33%). No complications or late reactions were reported in the (125)I group, whereas one case of hemorrhage and three cases of delayed stroke were observed in the (192)Ir group. CONCLUSIONS: The equal median survival times in these two brachytherapy groups with such different dose rate radiation schedules support the hypothesis that dose rate does not play a major role in the survival of patients with primary GBM.     

Local radiotherapy for patients with unresectable hepatocellular carcinoma

PURPOSE: To evaluate the response to local radiotherapy (RT) for unresectable hepatocellular carcinoma (HCC) and to analyze the dose-response relationship and the treatment-related morbidities. METHODS AND MATERIALS: Between 1998 and 2002, 59 patients who were treated with localized RT were evaluated. RT was delivered with a curative intent, and the radiation dose was 30-55 Gy (biologic effective dose of 39.0-70.2 Gy(10) using the alpha/beta ratio of 10 Gy) with 2-3 Gy as a daily dose. The tumor response was evaluated by the change in maximum tumor size on serial CT scans, and the morbidity was evaluated by the Common Terminology Criteria for Adverse Events v3.0. RESULTS: An objective tumor response was achieved in 39 of 59 patients (66.1%) with complete response (CR) in 5 patients and partial response (PR) in 34 patients. More than 50 Gy(10) had a significant response; CR or PR was 72.8% with >50 Gy(10) and 46.7% with < or =50 Gy(10) (p = 0.0299). The 2-year overall survival rate after RT was 27.4% (median survival time: 10 months), and this was affected by the tumor response (p = 0.0640); the 2-year overall survival rate after RT was 50.0% for CR and 21.8% for PR. There was no Grade 3 or 4 acute toxicity, and 3 patients (5.1%) developed gastric or duodenal ulcer. CONCLUSIONS: Radiotherapy for unresectable HCC resulted in 66.1% of tumor response with acceptable toxicity, and the radiation dose seems to be a significant prognostic factor in RT response for HCC.     

Microwave hyperthermia as an adjunct to radiation therapy: summary experience of 256 multifraction treatment cases

Results in 256 cases of malignant disease treated by multifraction combination hyperthermia-radiation therapy under the supervision of one physician are presented. The overall response rate was 94% including a 62% complete response. Complications specifically ascribed to hyperthermia were minor, and most side effects of combined treatment were radiation dose related. Tumor response was somewhat better for chest wall recurrence (72% CR) and for adenocarcinoma in general (64% CR), but no significant dependence on tumor site or type was found. Most patients were treated with low dose external radiation with hyperthermia given by air cooled microwave applicators or intracavitary antennae operating at 915 or 300 MHz, and some by interstitial microwave antennae plus 192 Ir. Results appeared to be independent of the microwave source employed. Response did depend on radiation dose: complete response rate with 4000 rad was 65%, and with 2000 rad was 42%.