Accelerated hyperfractionated radiotherapy for locally advanced cervix cancer.

PURPOSE: A phase II trial was designed to evaluate the toxicity and outcome of patients with locally advanced cervix cancer treated with accelerated hyperfractionated radiotherapy (AHFX). METHODS AND MATERIALS: In this prospective trial, AHFX doses of 1.25 Gy were administered twice daily at least 6 hours apart to a total pelvic dose of 57.5 Gy. A booster dose was then administered via either low-dose rate brachytherapy or external beam therapy to a smaller volume. All patients were accrued and treated at Peter MacCallum Cancer Institute (PMCI) between 1986 until April 1991. RESULTS: Sixty-one eligible patients were enrolled in this protocol; 2 (3.2%) had Stage IIB; 42 (68.9%) had Stage III; 8 (13.1%) had Stage IV and 9 (14.8%) had recurrent cervical cancer. Fifty-two patients (85%) completed the planned external beam without a treatment break. Thirty patients had acute toxicity that required regular medication. One patient died of acute treatment related toxicity. Fifty-five patients received booster therapy: 45 with intrauterine brachytherapy, 6 with interstitial brachtherapy, and 4 with external beam. The median follow-up of surviving patients was 6 years. Overall 5-year survival is 27% and 5-year relapse free survival is 36%. Nineteen patients died with pelvic disease and the actuarial local control rate was 66%. There were 8 severe late complications observed in 7 patients. Seven required surgical intervention (an actuarial rate of 27%). Five patients also required total hip replacement. CONCLUSIONS: The local control rate was favorable compared with other series that have used standard fractionation, although overall survival remained similar. The severe late complication rate was high for this protocol and higher than similar protocols reported in the literature.     

Accelerated fractionation radiotherapy for advanced head and neck cancer

Between 1981 and 1986, 89 patients with advanced head and neck squamous cancer were treated with a continuous accelerated fractionation radiotherapy (AFRT) regimen. Three fractions of 1.80 Gy, 4 h apart, were given on three treatment days per week (Monday, Wednesday, Friday), and the tumour dose was taken to 59.40 Gy in 33 fractions in 24-25 days. Acute mucosal reactions were generally quite severe, but a split was avoided by providing the patient with intensive support, often as an in-patient, until the reactions settled. Late radiation effects have been comparable to those obtained with conventional fractionation. The probability of local-regional control was 47% at 3 years for 69 previously untreated patients, whereas it was only 12% at one year for 20 patients treated for recurrence after radical surgery. Fifty-eight previously untreated patients with tumours arising in the upper aero-digestive tract were analysed in greater detail. The probability of local-regional control at 3 years was 78% for 17 Stage III patients and 15% for 31 Stage IV patients. This schedule of continuous AFRT is feasible and merits further investigation.     

Accelerated fractionation radiotherapy for laryngeal cancer, acute, and late toxicity.

The acute toxicity of an accelerated radiotherapy scheme was compared with a conventional schedule. Eighteen patients with squamous cell carcinoma of the larynx were treated with accelerated fractionation radiotherapy. An average reduction of overall treatment time of 11 days was accomplished by giving 2 fractions a day during the last part of the treatment. Total dose and fraction dose were left unchanged. Acute reactions of skin and mucosa in these patients were compared with those in 40 patients treated with a conventional fractionation scheme, that is, 2 Gy per fraction, 5 fractions per week, to a total dose of 64-70 Gy. Acute reactions were maximal between 5 and 7 weeks after the start of treatment. Complete healing occurred within 3 months in all patients. Mucosal reactions and, as a consequence, dysphagia were clearly increased in those patients treated with accelerated fractionation. For confluent mucositis an ED50 of 66 Gy was calculated compared to 69 Gy for conventional fractionation. To a lesser degree, skin toxicity was also enhanced in the patients treated with the accelerated schedule. Severe edema of the laryngeal mucosa occurred only in patients treated to a total dose of 68 or 70 Gy and was somewhat more frequent with accelerated fractionation (4/10) than with conventional fractionation (4/24). One patient in the accelerated fractionation group underwent laryngectomy for persistent edema and laryngeal necrosis. No severe late skin reactions were observed. It can be concluded that the fractionation schedule tested in this study is feasible. Further shortening of overall treatment time without reduction of total dose will likely lead to unacceptable acute and, possibly, also late toxicity.     

Hypothyroidism after radiotherapy for laryngeal cancer.

PURPOSE: To investigate the incidence of hypothyroidism after radiotherapy of laryngeal cancer, including the possible factors that could predict the onset of hypothyroidism. MATERIALS AND METHODS: We report this study on patients treated by radiotherapy as part of the treatment for laryngeal cancer in the Department of Oncology in Eastern Finland. Sixty-five males and seven females were treated with radiotherapy between 1974-1995.Thyroid function was determined by measuring serum thyroid stimulating hormone, and serum free thyroxine (FT4). The studied risk factors for hypothyroidism included age, treatment modalities, radiation dose and energy, height of the radiation field, and follow-up time. RESULTS: Hypothyroidism was detected in 17 (24%) of the 72 patients. Hypothyroidism was clinically unsuspected in all but one patient. Hypothyroidism was more common, if the height of the radiation field was >/=7 cm, or the patient had been operated. Hypothyroidism was less common if less than a half of the thyroid bed was irradiated. CONCLUSION: The detection of hypothyroidism clinically is difficult, and the rate of hypothyroidism warrants routine assessment of thyroid function after irradiation of laryngeal cancer.     

Accelerated concomitant boost radiotherapy and chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the feasibility and efficacy of concomitant boost radiotherapy (RT) plus cisplatin-based chemotherapy compared with standard fractionation RT for patients with advanced nasopharyngeal cancer. PATIENTS AND METHODS: From 1988 through 1999, 50 patients with American Joint Committee on Cancer stage II-IVb nasopharyngeal carcinoma were treated with 70-Gy concomitant boost RT (1.8 Gy/d, weeks 1 through 6; 1.6 Gy second daily fraction, weeks 5 through 6) and two cycles of concurrent cisplatin 100 mg/m(2) days 1 and 22. Thirty-seven patients also received three cycles of cisplatin-based adjuvant chemotherapy. These 50 patients were compared with a nonrandomized cohort of 51 patients with nasopharyngeal cancer treated with 70-Gy standard fractionation RT (1.8 Gy/d) without chemotherapy from 1988 through 1995. The groups were well matched for prognostic factors except stage, for which the concomitant boost RT/chemotherapy group was more advanced (54%, T3-4; 54%, N2-3; 44%, stage IV) compared with the standard RT group (31%, T3-4, P =.03; 22%, N2-3, P <.001; 20%, stage IV, P <.01). RESULTS: With a median follow-up of 42 months (range, 12 to 129 months), the 3-year actuarial local control, progression-free survival, and survival rates were 89% v 74% (P <.01), 66% v 54% (P =.01), and 84% v 71% (P =.04) for the concomitant boost RT/chemotherapy group and the standard RT patients, respectively. Acute grade 3 mucositis was more prevalent with combined therapy, 84% v 43% (P <.001), resulting in a higher rate of temporary gastrostomy tube placement, 46% v 20% (P <.01). CONCLUSION: Concomitant boost RT with cisplatin-based chemotherapy is feasible and improves local-regional control as well as survival for patients with advanced nasopharyngeal cancer compared with standard RT alone.     

加速分割放疗配合同期化疗治疗晚期鼻咽癌

背景与目的：临床研究表明,常规分割放射疗法治疗晚期鼻咽癌(nasopharyngeal carcinoma,NPC)的疗效不理想,采用非常规分割放疗以及放疗配合化疗治疗晚期NPC成为目前研究的重点。本研究的目的是探讨加速分割放疗以及同期化疗治疗晚期NPC的治疗效果和放射反应。方法：将我院1993年6月。1996年6月经病理检查证实、首程接受放射治疗的416例晚期NPC患者随机分为3组：加速分割放疗(accelerated fractionated radiotherapy,AF)组138例,每周照射6天,每天1次,每次180-190cGy,共46-49天,总剂量7400-7600cGy;加速分割放疗同期化疗(accelerated fractionated radiotherapy with concurrent chemotherapy,AFC)组139例,放疗方法同AF组,每周加顺铂和5-氟尿嘧啶各10次;常规分割放疗(conventional fractionated radiotherapy,CF)组139例,每周照射5天,每天1次,每次200cGy,总剂量7000--7500cGy。观察各组患者的局部复发率,5年生存率和放射反应。结果：随访超过5年,AF组和AFC组的局部复发率低于CF组,分别为16．7％     

Accelerated superfractionated radiotherapy with concomitant boost for invasive bladder cancer

PURPOSE: To determine the toxicity and clinical effectiveness of accelerated superfractionated radiotherapy with delayed concomitant boost (ASCBRT) in locally invasive carcinoma of the bladder. METHODS AND MATERIALS: Between July 1997 and December 2001, 87 patients (unsuitable or refusing cystectomy) with invasive bladder cancer underwent ASCBRT. The mean patient age was 66 years (range 40-90). The stage distribution was as follows: 2 T1, 51 T2, 13 T3, and 21 T4. Initially, the whole pelvis was treated by 1.8-Gy conventional daily fractions up to a total dose of 45 Gy. A small field boost covering gross disease was added as a second daily fraction (1.5 Gy) during the last 3 weeks of the 5-week schedule up to a total dose of 67.5 Gy. The interfraction interval was a minimum of 6 h. The patients were evaluated in follow-up for toxicity, local control, and survival. RESULTS: All but 2 patients completed the study protocol. Grade 3 acute urinary toxicity was observed in 2 patients. Grade 2 and 3 late bladder toxicity was observed in 12 patients and 1 patient, respectively. Grade 2 and 3 late bowel toxicity was observed in 5 and 3 patients, respectively. The 3-year actuarial local control, distant disease control, cause-specific survival, and overall survival rate was 64%, 78%, 58%, and 46%, respectively. Multivariate analysis revealed T stage as independent predictor of complete response. For Stage T2 and T3, the 3-year local control rate was 77% and 48%, respectively. At the last follow-up, 53 patients (61%) were still alive with a survival time between 6 and 62 months. CONCLUSION: ASCBRT is feasible with acceptable tolerance even in relatively old patients with Stage T3 or greater tumor. The encouraging locoregional control and survival results of this institutional experience, favorable compared with conventional radical and other accelerated fractionated (with or without a concomitant boost) RT series, make ASCBRT worthy of further study in a Phase III trial.     

Function-sparing surgery of laryngeal cancer after radiotherapy

Economical sparing surgery following radiation treatment was carried out in 284 cases of laryngeal cancer. Application of a complex of diagnostic procedures for determining tumor boundaries before and during surgery as well as some improved preoperative radiation treatment (irradiation in a high-pressure oxygen chamber) and surgical methods showed that sparing surgery gives good results, as far as function of the treated organ and patient's survival are concerned.     

Accelerated hyperfractionated radiotherapy and concurrent protracted venous infusion chemotherapy in locally advanced head and neck cancer

Concurrent radiotherapy and chemotherapy result in a significant benefit with respect to induction chemotherapy followed by radiotherapy or radiotherapy alone, although with a significant increase of toxicity. To discover a more tolerated and effective chemoradiation regimen, the feasibility and efficacy of a hyperfractionated accelerated irradiation with concurrent protracted venous infusion chemotherapy was investigated. Sixty-five patients with advanced head and neck cancer underwent a definitive (53 patients) or a postoperative adjuvant (12 patients) chemoradiation treatment. Chemotherapy consisted of an intravenous protracted infusion of 5 and 200 mg/m /d cisplatin and 5-fluorouracil, respectively. Radiotherapy consisted of a split-course accelerated hyperfractionation of two 150-cGy (split twice a day) or three 100-cGy fractions per day (split three times a day) at more than 6-hour intervals, for 2 weeks followed, after a 1-week interruption, by 2-to-3-week treatment, with the same fractionation schedule, to a total dose of 60 Gy to 69 Gy. Confluent mucositis was tolerable and was the cause of treatment delay of more than 10 days in only 20% of patients. Grade 3 or greater systemic toxicity occurred only in 9 of 65 (14%) patients and was never the cause of drug dose reduction. Complete responses were observed in 69% of patients with gross diseases. At a median follow-up of 43.5 months, 45% of patients were alive and free of disease and 38% died of cancer. The 5-year actuarial local regional failure was 35%. The 5-year actuarial disease-specific survival was 50%. Preservation of larynx function was achieved in 47% of living patients and in 74% of all patients, with advanced tumors of the laryngopharynx. The long-term results of this study suggest that this chemoradiation regimen has the potential of achieving a significant improvement over standard therapy while avoiding significant toxicity.     

Accelerated superfractionated radiotherapy with concomitant boost for locally advanced head-and-neck squamous cell carcinomas

PURPOSE: A growing body of evidence supports the efficacy of accelerated superfractionated radiotherapy with concomitant boost for advanced head-and-neck carcinomas. This study represents a single-institution experience, performed to identify the factors influencing tumor control, survival, and toxicity. MATERIALS AND METHODS: Between 1988 and 1999, 133 patients with primary squamous cell head-and-neck carcinoma underwent accelerated superfractionated radiotherapy using a concomitant boost. The concomitant boost in this regimen was delivered using reduced fields delivered 3 times weekly in a twice-daily schedule during the final phase. The total radiation dose ranged from 64.8 Gy to 76.5 Gy (mean 71.1). Patients were evaluated in follow-up for local control and late toxicity. Multivariate analysis of treatment and patient parameters was performed to evaluate their influence on toxicity, local control, and overall survival. RESULTS: With a mean follow-up of 37 months, the actuarial overall survival rate for the entire group at 5 years was 24% and the local control rate was 57%. The tumor volume was the most significant predictor of local control, such that each 1-cm(3) increase in volume was associated with a 1% decrease in local control. For patients with tumor volumes 30 cm(3), the 5-year disease-specific survival rate was 52% and 27% (p = 0.004) and locoregional control rate was 76% and 26% (p <0.001), respectively. Seventy-six patients with a minimum of 12 months and median of 39 months toxicity follow-up were studied for late effects. None of these patients experienced Grade 4 or 5 toxicity. The actuarial rate of significant toxicity (Grade III or greater) was 32% at 5 years. Of the toxicities observed, xerostomia (19%) was the most common. Multivariate analysis revealed N stage and dose as independent predictors of Grade 3 effects. CONCLUSION: The locoregional control and survival for patients in this institutional experience compare favorably to other published reports. Tumors of the larynx had the best prognosis. Larger volume tumors were associated with significantly lower local control and survival. Significant late effects were related to dose and nodal status.     

Palliative prostate radiotherapy for symptomatic advanced prostate cancer

Background and purpose

To report the results for the use of short-course palliative radiotherapy to the prostate for localised symptoms.

Materials and methods

Fifty-eight patients were identified from radiotherapy records between 2003 and 2007. Data were collected retrospectively on patients’ demographics, radiotherapy details and response. Symptoms and toxicity were scored, retrospectively, according to the following scale: 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, and 3 = severe symptoms.

Results

All the 58 patients had advanced prostate carcinoma. The median age at radiotherapy was 76.6 years (range 54-91). Fifty-six patients (97%) had hormone refractory disease. Twenty-seven patients (47%) had evidence of metastatic disease. 20Gy in 5 fractions was the most commonly used fractionation. The most frequent baseline symptom was haematuria (54%). Eighty-nine percent (31/35) of the patients had a complete or partial resolution of symptoms at 4 months. Response rates for individual symptoms (including unknown responses) were: rectal symptoms (75%), pelvic pain (69%), urinary obstruction (54%) and haematuria (42%). A >50% reduction in PSA occurred in five patients. Toxicity was mild to moderate only and was self-limiting.

Conclusion

Palliative radiotherapy to the prostate gland for local symptoms appears to be an effective means of palliation with minimal toxic side effects. Prospective studies are now required to assess its benefits in more detail.     

加速分割放疗同步卡培他滨化疗治疗晚期鼻咽癌

背景与目的:目前,常规分割放疗治疗晚期鼻咽癌疗效不甚理想,5年生存率仅在23%～40%之间。为此,本研究探讨加速分割放疗同步卡培他滨化疗治疗晚期鼻咽癌的疗效和毒副反应。方法:82例晚期鼻咽癌患者,采用抽签法随机分为加速分割放疗同步卡培他滨化疗组和常规分割放疗组。同步放化疗组每周照射6d,每天照射1次,每次照射剂量为1.8～1.9Gy,总剂量为72～76Gy,且在放疗同时给予卡培他滨化疗;常规分割放疗组每周照射5d,每天照射1次,每次照射剂量为2Gy,总剂量亦为72～76Gy。结果:同步放化疗组的完全缓解率为92.7%,显著高于常规分割放疗组的71.0%(P<0.05)。同步放化疗组的局部复发率(17.1%)显著低于常规分割放疗组(36.5%)(P<0.05),而其远处转移率(19.5%)亦显著低于常规分割放疗组(41.5%)(P<0.05)。两组的5年生存率分别为63.5%和41.3%,同步放化疗组显著优于常规分割放疗组(P<0.05)。而同步放化疗组的骨髓抑制及急性放射反应发生率则显著高于常规分割放疗组(P<0.05)。结论:加速分割放疗同步卡培他滨化疗对晚期鼻咽癌有较好的疗效,且其毒副反应能耐受。     

Accelerated postoperative radiotherapy with weekly concomitant boost in patients with locally advanced head and neck cancer.

BACKGROUND AND PURPOSE: To assess the feasibility and efficacy of accelerated 66-Gy postoperative radiotherapy (PORT) using a single-fraction regimen from Mondays to Thursdays and a concomitant boost on Friday afternoon sessions in patients with locally advanced head and neck cancer (LAHNC). PATIENTS AND METHODS: Between December 1997 and June 2002, 89 consecutive patients with pT1-pT4 and/or pN0-pN3 LAHNC were included. PORT was indicated in patients with positive surgical margins, T4 tumors, or extracapsular nodal infiltration. RT consisted of 66 Gy (2 Gy/fr) in 5 weeks and 3 days. Median follow-up was 21 months (range 2-59). RESULTS: Acute morbidity was acceptable: grade 3 mucositis in 20 (22%) patients, grade 3 dysphagia in 22 (25%) patients, and grade 3 skin erythema in 18 (20%) patients. Median weight loss was 2 kg (range 0-14.5). No grade 4 toxicity was observed. Late effects included grade 3 xerostomia in 6 (7%) patients, and grade 3 edema in 2 (2%) patients. Median time to locoregional relapse was 10 months (range 2-21). Two-year overall, cause-specific, and disease-free survival rates were 70% (95% confidence interval (CI) 59-81), 75% (95% CI 64-86), and 63% (95% CI 52-74), respectively. The 2-year actuarial locoregional control rate was 80% (95% CI 70-90). Distant metastasis probability at 4 years was 38% (95% CI 20-56). Multivariate analysis revealed that pT-classification (pT1-2 vs. pT3-4) and extranodal extension (0, 1 vs. 2 or more) were the two factors independently influencing the outcome. CONCLUSIONS: We conclude that reducing the overall treatment time using an accelerated PORT schedule including a once-weekly concomitant boost (six fractions per week) is easily feasible with excellent local control. Acute and late RT-related morbidity is acceptable. Given the disease progression pattern (distant metastases), adjuvant chemotherapy should be considered.     

Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter Phase III study

PURPOSE: To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx. METHODS AND MATERIALS: Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a "biphasic concomitant boost" schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis. RESULTS: From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% +/- 4% for CF and 78% +/- 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% +/- 5% for CF and 64% +/- 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% +/- 4% and 27% +/- 6% for CF and AF, respectively (p = 0.10). CONCLUSION: Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection; however, AF might be an option for patients who delay starting RT.