Hypofractionated radiotherapy in prostate cancer

In regards to prostate cancer, the classic radiotherapy dose ranges from 70–80 Gy, administered in daily 2-Gy fractions. However, when taking into account the particular radiobiological model of prostate cancer cells, one realizes that there is a potential theoretical advantage to delivering a greater biological effective dose per treatment in a lower number of fractions. Both recent and older publications have attempted to explore this treatment option. This critical review comprehensively examines the current state of knowledge concerning hypofractionated radiotherapy in prostate cancer.     

Hypofractionated radiotherapy with carbon ion beams for prostate cancer

PURPOSE: Analysis of the results of hypofractionated conformal carbon ion radiotherapy for localized prostate cancer was performed, with special regard to normal tissue morbidity and biochemical relapse-free rate (bNED). METHODS AND MATERIALS: Analysis was performed for 201 patients treated with the dose fractionation regimen established during three clinical trials performed between June 1995 and February 2004. Outcomes were measured in terms of toxicity, survival, freedom from local recurrence, and bNED. RESULTS: No Grade 3 or higher toxicities were observed in either the rectum or genitourinary system, and the incidences of Grade 2 rectum or genitourinary morbidity were only 1.0% and 6.0%, respectively. The overall 5-year biochemical relapse-free survival was 83.2% without any local recurrence. Gleason score, initial PSA, and T stage were all significant prognostic factors for bNED, which was 97.1% in patients with Gleason score < or =7 and initial PSA <20 ng/mL. CONCLUSION: Hypofractionated carbon ion radiotherapy with the established dose fractionation regimen yielded satisfactory bNED without local recurrence and with minimal morbidity. Long-term results are necessary to confirm the utility of carbon ion radiotherapy in the treatment of localized prostate cancer.     

Hypofractionated radiotherapy for localised prostate cancer. Review of clinical trials

Over the last 10 years the radiobiology of prostate cancer has been studied both in experimental research and in clinical trials of hypofractionated radiotherapy. Unlike most cancers, the α/β ratio of the prostatic carcinoma is probably lower than that of the healthy organs around the gland, although there is no agreement as to how low this α/β really is. This peculiarity implies that, theoretically, a hypofractionated schedule would increase the therapeutic gain of radiotherapy. Until now, following four published randomised trials, hypofractionated radiotherapy has shown results in terms of acute and chronic toxicity and tumour control similar to those obtained with conventionally fractionated radiotherapy. However, these studies are not conclusive. The two studies that involved significant follow-up used 2D technique and delivered low total equivalent dose. On the other hand, the two most recent trials, which administered total equivalent doses ⩾78 Gy with modern techniques (IMRT, IGRT), involved the disadvantage of small samples and a short follow-up period. The results of ongoing randomised trials are necessary to confirm the advantages of hypofractionation over normofractionated radiotherapy. The impact of hypofractionated radiotherapy on the patient’s health-related quality of life, and on transports and health care costs, should also be investigated. Supported by an unrestricted educational grant from Merck Serono     

非小细胞肺癌大分割放疗

 大分割三维适形放疗（3DCRT）为进一步改善非小细胞肺癌（NSCLC）患者局部控制率、生存率及生活质量提供了可能,但最佳剂量分割方案尚不明确,有待进一步研究。立体定向体部放疗（SBRT）在早期NSCLC中取得了令人满意的局部控制率和生存率,且不良反应在可接受的范围内,有望成为早期NSCLC患者新的标准治疗手段。     

Hypofractionated accelerated radiotherapy using concomitant intensity-modulated radiotherapy boost technique for localized high-risk prostate cancer: acute toxicity results

PURPOSE: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. METHODS AND MATERIALS: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score >/=8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. RESULTS: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. CONCLUSION: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.     

Hypofractionated conformal radiotherapy in carcinoma of the prostate: five-year outcome analysis

PURPOSE: Recent publications have indicated that the alpha/beta ratios for carcinoma of the prostate are much lower than had originally been thought, suggesting that prostate cancer may be highly sensitive to fraction size. We have reviewed our unique experience of the use of 3.13 Gy fractions in a large cohort of men treated homogeneously in a single institute. MATERIALS AND METHODS: The outcome for 705 men with T1-T4, N0, M0 prostate cancer who received conformal radiotherapy between 1995 and 1998 at this center was analyzed. No patient received hormonal manipulation. Mean age was 68 years (range: 49-84 years). Median pretreatment PSA was 13 ng/mL (range: 0.6-270 ng/mL). Disease characteristics were as follows: Stage T1, 125 (18%); T2, 365 (52%); T3/4, 215 (30%); Gleason 2-6, 463 (66%); Gleason 7-10, 242 (34%); pretreatment PSA < or =10 ng/mL, 291 (41%); 10 to < or =20, 228 (32%); >20, 186 (27%). Median follow-up was 48 months (range: 1-82 months). Biochemical-free survival (bNED) was defined by the American Society for Therapeutic Radiology and Oncology consensus definition. Radiotherapy was delivered to a planning target volume (prostate plus all/base of the seminal vesicles dependent on risk criteria with a 1-cm margin) with a 4-field conformal technique to a dose of 50 Gy in 16 daily fractions over 22 days. RESULTS: The 5-year bNED survival was significantly associated (p < 0.001) with pretreatment PSA, stage, and Gleason score. Five-year bNED rates with respect to pretreatment characteristics were as follows: 73% (PSA < or =10), 52% (>10-20), 35% (>20), 64% (Stage T1/2), 38% (T3/4), 61% (Gleason score 2-6), and 46% (Gleason > or =7). When patients were grouped into good (Stage T1/2, PSA < or =10 ng/mL, and Gleason score <7) (n = 181), intermediate (1 raised value) (n = 247), or poor (2 or more raised values) (n = 277) prognostic groups, the bNED was, respectively, 82%, 56%, and 39%. Radiation Therapy Oncology Group Grade > or =2 bowel toxicity was 5% and bladder 9%. CONCLUSIONS: These data indicate that the delivery of a relatively low total dose using a hypofractionated regime results in similar tumor control and normal-tissue toxicity to 65-70 Gy delivered in 1.8-2 Gy fractions. These data suggest that this is an acceptable regime for good-prognosis patients. However, because of the evidence for a dose effect at doses above 70 Gy with "conventional fractionation," we are now treating intermediate- and poor-risk patients within a hypofractionated dose escalation trial to 60 Gy in 20 fractions using intensity- modulated radiotherapy.     

体部大分割放射治疗肝转移癌疗效及安全性

目的 分析应用体部大分割放疗技术治疗肝转移癌的疗效及安全性。方法 回顾性分析2007-2016年间本院收治的行体部大分割放疗的45例肝转移癌患者的病历资料。其中男20例,女25例,中位年龄58岁(25~83岁),中位KPS=80。原发肿瘤部位以结直肠癌(14例)、乳腺癌(9例)和肺癌(6例)为主。观察并分析体部大分割放疗后的效果和不良反应。结果 中位随访时间为23.5个月,中位生存期26.0个月(95%CI为21.4~30.6)。45例患者中21例发生肝外转移,共治疗52个肝转移病灶,行1个病灶放疗者34例。剂量分割为45 Gy分3次、60 Gy分10~15次。中位GTV和PTV分别为 10.1 cm³(0.3~175.2 cm³)和29.8 cm³(5.0~209.6 cm³)。17例患者的肝脏CT图像与MRI图像融合,43例患者采用IMRT技术。中位PTV剂量为60 Gy (40~60 Gy),BED为90 Gy (60~132 Gy)。放疗后1年肿瘤局部控制率、无瘤生存率和总生存率分别为94%、27%和91%。末次随访时,6例患者病死于肝转移和肝功能异常。结论 体部大分割放疗对肝转移癌是安全有效的。     

Hypofractionated radiotherapy for sarcomas

In an effort to improve local control in the radiation treatment of sarcomas, up to 7 weekly fractions of 6.6 Gy each were administered to 64 patients. They were divided into two groups: Group A consisted of 37 patients with measurable disease who achieved a partial response rate of 22%, with no complete responses. Group B consisted of 27 postoperative patients with varying degrees of completeness of surgical excision, two have relapsed locally to date. Early radiation damage was documented in 26%, but was not a dose-limiting or incapacitating event in any case. Late normal tissue damage occurred in 23 out of 32 evaluable patients (72% of those at risk), and was a cause of serious morbidity in 6 patients. Response rates were low in Group A compared with other series, but in Group B the local recurrence rate is comparable with other centers using "conventional" fractionation. No apparent improvement in therapeutic gain was demonstrated for large weekly fractions.     

Hypofractionated intensity-modulated radiotherapy (70 gy at 2.5 Gy per fraction) for localized prostate cancer: long-term outcomes

PURPOSE: To analyze the long-term relapse-free survival and toxicity rates in patients treated with hypofractionated intensity-modulated radiotherapy. METHODS AND MATERIALS: The study sample includes the first 100 consecutive localized prostate cancer patients treated to 70.0 Gy at 2.5 Gy per fraction. The median follow-up was 66 months (range, 3 to 75 months). Biochemical failure was the study endpoint, using both the ASTRO definition (A-bRFS) and the alternate "nadir + 2 ng/mL" definition (N-bRFS). RTOG scores were used to assess toxicity. RESULTS: The 5-year A-bRFS and N-bRFS rates were 85% (95%CI, 78-93%) and 88% (95%CI, 82-95%) for all cases, respectively. For low, intermediate and high-risk disease, the 5-year A-bRFS rates were 97%, 88%, and 70%. The corresponding 5-year N-bRFS rates were 97%, 93%, and 75%, respectively. The acute rectal toxicity scores were 0 in 20, 1 in 61, and 2 in 19 patients. The acute urinary toxicity scores were 0 in 9, 1 in 76, and 2 in 15 patients. The late rectal toxicity scores were 0 in 71, 1 in 19, 2 in 7, and 3 in 3 patients. The actuarial late Grade 3 rectal toxicity rate at 5 years was 3%. A number of the toxicities observed either resolved spontaneously or were corrected. At last follow-up, the rate of combined Grades 2 and 3 late rectal toxicity at 5 years was only 5%. The late urinary toxicity scores were 0 in 75, 1 in 13, 2 in 11, and 3 in 1 patients. The actuarial late Grade 3 urinary toxicity rate at 5 years was 1%. CONCLUSION: With a median follow-up of 66 months, the long-term results after high-dose hypofractionation are excellent. Late toxicity, urinary and rectal, has been limited. High-dose hypofractionation is an alternative dose escalation method in the treatment of localized prostate cancer.     

Radical radiotherapy for prostate cancer

External beam radiotherapy is one of the curative treatment options for localised prostate cancer. This article will describe recent advances in prostate radiotherapy, focussing on the results of randomised trials which have addressed the role of radiation dose escalation and of adjuvant hormone therapy. Current controversies will then be considered, including the merits of radiotherapy in comparison with alternative approaches to early prostate cancer, and the possible role of adjuvant radiation following surgery. Finally, future developments will be described, including hypofractionation and dose individualisation, which have the potential to further improve the outcome of external beam radiotherapy for prostate cancer.     

Definitive radiotherapy for prostate cancer

The probability of extraprostatic disease may be estimated based on clinical T-stage, pretreatment prostatic-specific antigen, Gleason score, and percent positive core biopsies. Patients with disease confined to the prostate may be treated with either prostatectomy or radiotherapy (RT). Patients with extraprostatic disease without evidence of distant metastases are best managed with RT. RT consisting of either external beam and/or brachytherapy results in a relatively high likelihood of cure, particularly for those with low- and intermediate-risk disease. The impact of elective nodal RT on survival is unclear. Dose escalation results in improved biochemical relapse-free survival compared with standard dose RT. Androgen deprivation therapy likely improves the probability of disease control in patients with high-risk cancers.     

Hypofractionated accelerated radiotherapy in osteogenic sarcoma.

A method of hypofractionated accelerated radiotherapy (3 weekly fractions of 6 Gy over 2 weeks to a total tumor dose of 36 Gy) was used as single modality in 14 patients with osteogenic sarcoma for palliative treatment of the primary tumor site (six cases) or skeletal metastases (15 sites). A durable response, radiologically assessed, was obtained in 17 of the 21 (81%) irradiated sites. When this irradiation modality was combined with chemotherapy, to treat patients presenting with synchronous metastases (eight cases) or refusing amputation (five cases), a radiologically assessed response was observed in 12 of 13 (92%). In no case did a local recurrence occur before surgery or death because of progressive disease elsewhere. Of the seven patients who later had to undergo ablative surgery, a 100% and 95% tumor necrosis was observed in 6 and 1, respectively. Because of intralesional resection of primary osteogenic sarcoma after preoperative chemotherapy, seven additional patients were irradiated. None recurred at the level of the primary site. Although effective in inducing remission of osteogenic sarcoma, this irradiation method produced severe damages to normal tissues in a high proportion of patients.     

Hypofractionated intensity-modulated radiotherapy (70 Gy at 2.5 Gy per fraction) for localized prostate cancer: Cleveland Clinic experience

PURPOSE: To study the outcomes in patients treated for localized prostate cancer with 70 Gy delivered at 2.5-Gy/fraction within 5 weeks. METHODS AND MATERIALS: The study sample included all 770 consecutive patients with localized prostate cancer treated with hypofractionated intensity-modulated radiotherapy at the Cleveland Clinic between 1998 and 2005. The median follow-up was 45 months (maximum, 86). Both the American Society for Therapeutic Radiology and Oncology (ASTRO) biochemical failure definition and the alternate nadir + 2 ng/mL definition were used. RESULTS: The overall 5-year ASTRO biochemical relapse-free survival rate was 82% (95% confidence interval, 79-85%), and the 5-year nadir + 2 ng/mL rate was 83% (95% confidence interval, 79-86%). For patients with low-risk, intermediate-risk, and high-risk disease, the 5-year ASTRO rate was 95%, 85%, and 68%, respectively. The 5-year nadir + 2 ng/mL rate for patients with low-, intermediate-, and high-risk disease was 94%, 83%, and 72%, respectively. The Radiation Therapy Oncology Group acute rectal toxicity scores were 0 in 51%, 1 in 40%, and 2 in 9% of patients. The acute urinary toxicity scores were 0 in 33%, 1 in 48%, 2 in 18%, and 3 in 1% of patients. The late rectal toxicity scores were 0 in 89.6%, 1 in 5.9%, 2 in 3.1%, 3 in 1.3%, and 4 in 0.1% (1 patient). The late urinary toxicity scores were 0 in 90.5%, 1 in 4.3%, 2 in 5.1%, and 3 in 0.1% (1 patient). CONCLUSION: The outcomes after high-dose hypofractionation were acceptable in the entire cohort of patients treated with the schedule of 70 at 2.5 Gy/fraction.     

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.     

Hypofractionated intensity-modulated radiotherapy in locally advanced unresectable pancreatic cancer: A pilot study

PurposeTo test feasibility and safety of hypofractionated intensity modulated radiotherapy (H-IMRT) in pancreatic adenocarcinoma (PAC) treatment.MethodsPatients with unresectable nonmetastatic PAC were prospectively enrolled on a pilot study. Patients received H-IMRT to gross tumor volume to a total dose of 52 Gy (4 Gy/fraction). Toxicity rates, duodenal dosimetric parameters, and clinical outcomes were evaluated.ResultsTen patients received H-IMRT regimen. Objective tumor response was recorded in all patients but one. Gastrointestinal toxicity was the most common acute side effect and its severity moderately correlated with duodenal maximum dose (ρ = 0.46) and percentage of duodenal volume exposed to 5 Gy (ρ = 0.46). The 1-year overall and disease-free survival were 83.3% and 68.6%, respectively.ConclusionH-IMRT seems to guarantee a high local control rate without severe toxicity. Its use in unresectable nonmetastatic PAC needs to be further investigated.