术前,术后放疗的直肠癌治疗中作用的评估和比较

目的：评估和比较辅助性术前、术后放疗在直肠癌治疗中的作用。方法：１９８８年２月～１９９５年２月收治经病理证实的直肠癌１７６例,配合手术分别采用术前单次放疗、术前常规放疗和术后放疗。术前单次放疗组３８例,剂量为５Ｇｙ,并于放疗后４８ｈ内手术;术前４０Ｇｙ常规放疗组４３例,多为临床晚期（Ｔ３～４占６０．５％）,中位剂量４０Ｇｙ,放疗后休４周再行手术;术后放疗组９５例,以病变晚期和淋巴结阳性为主（Ｔ３～４占６２．１％,Ｔ２～４Ｎ＋占８１．１％）,采用中位剂量５４Ｇｙ常规分割,疗程约６周,手术后３～４周开始接受放疗。结果：全部病例平均随访８４个月,Ｋａｐｌａｎ－Ｍｅｉｅｒ法计算生存率。术前单次放疗组３年、５年局部复发率分别为７８．９％和５０．０％,常规术前４０Ｇｙ放疗组为６７．４％和５１．１％;术后放疗组为５８．９％和     

Percutaneous radiotherapy for low-risk prostate cancer: options for 2007

Technical developments of radiotherapy (RT) over the recent years yielded in better conformation to the target volume thus increasing the therapeutic ratio and decreasing side effects. This paper discusses these options for low-risk prostate cancer. There has been evidence from randomized trials, that for low-risk PCA doses >70 Gy are significant better in case of biochemical disease-free survival (bNED). Image-guided radiotherapy (IGRT) has been proven in several studies for reduced safety margins around the prostate target volume. Intensity-modulated radiotherapy (IMRT) allow treatment with higher doses and 5-year results are reported from several studies. Data from several randomized trials about adjuvant RT after radical prostatectomy (RP) have been reported. In two phase-III trials a significant advantage of 20% bNED was demonstrated for doses between 76 and 79 Gy compared with 70 Gy. Using IGRT, the safety margin around the prostate can be reduced for about 30–50%. Doses of >80 Gy can be given safely to the prostate with IMRT and <5% grade-III/IV late side effects. Adjuvant RT for positive margins after RP has been of proven advantage. Three phase-III trials achieved a significant better bNED of 20% for 5 years. The effect of doses >70 Gy have been proven for low-risk PCA. IGRT resulted in reduced safety margins and a decrease of acute and late side effects. The addition of IMRT allowed higher doses to the prostate. Adjuvant RT after RP for positive margins achieved a significant better bNED.     

A prospective case series assessing the Imperial College London intraoperative radiotherapy protocol for advanced rectal cancer: an IDEAL phase 2a study

Aim

Intraoperative radiotherapy (IORT) decreases local recurrence rates for advanced rectal cancer. Nevertheless, utilization of IORT is limited due to the associated logistical and financial challenges. The aim of this study is to describe the development and delivery of a novel IORT protocol for advanced rectal cancer that overcomes these difficulties in the context of the early phase of an IDEAL 2a study. The primary outcome measure was the ability to deliver IORT using this novel protocol with IORT-related toxicity as the secondary outcome measure.

Method

Consecutive patients with advanced rectal cancer expected to have involved (R1) resection margins were enrolled. After resection, 12 Gy low-energy photon IORT was delivered using the Axxent device with a custom-designed elliptical spherical balloon applicator.

Results

Six patients with a median age of 47 years (range 33–88 years; five women) were enrolled between 2018 and 2019. The indication was advanced cancer in four patients and atypical invasive pelvic side wall lymph nodes in two. IORT was successfully delivered in all cases. No toxicity was encountered. Three advanced cancer patients had R1 resection and one had complete resection (R0); resection margin status could not be established for the two lymph node cases. Five patients were alive at 3.4 (2.9–4.1) year follow-up. None of the R1 cases recurred.

Conclusion

This is the first study to describe a novel IORT protocol using low-energy photon IORT for advanced rectal cancer. IORT could be delivered in all cases and no IORT-related toxicity was encountered. Available oncological outcome data are encouraging, but further studies will be necessary to determine the oncological effectiveness of this protocol.     

Hypofractionated Stereotactic Radiotherapy for Malignant Glioma: A Phase I/II Study

In order to shorten treatment time for patients with newly diagnosed supratentorial malignant glioma, a phase I study of LINAC-based hypofractionated stereotactic radiotherapy (SRT) was initiated in September 1991. Nineteen adult patients entered the study. They were treated with 23 MV photons using a single-isocenter arc technique. Six patients received 5 × 5 Gy, 11 received 5 × 6 Gy, and 2 received 5 × 7 Gy over 1 week. Treatment plans were normalized to 100% at the isocenter. Target volume encompassed the tumor with a margin of 1.5–2 cm and was surrounded by the 80% isodose. Five patients had anaplastic astrocytoma and 14 had glioblastoma multiforme. Median tumor volume before SRT was 20.4 cm³. A matching group of 19 patients who received conventionally fractionated radiotherapy (CFRT) was selected in order to compare time to progression and survival. CFRT was applied with daily fractions of 2 Gy up to 60 Gy in 6 weeks. No chemotherapy was given. Seven of 19 patients developed acute grade III or IV toxicity (RTOG central nervous system toxicity criteria) and had to be treated with high-dose steroids and/or mannitol within 8 weeks after SRT (1 of 6 after 5 × 5 Gy, 5 of 11 after 5 × 6 Gy, and 1 of 2 after 5 × 7 Gy). In contrast, only 2 patients had signs of late toxicity. No radionecrosis was observed. Median time to progression was 5 months, median survival 7 months (CFRT: 7 and 11 months, p>0.1). One-year survival rate was 32% versus 37%. However, it was 0% after 5 × 5 Gy, but 40% after 5 × 6 or 7 Gy (p = 0.06). In conclusion, toxicity of SRT with 5 × 6 or 7 Gy was not acceptable. The 5 × 5 Gy regimen was tolerable, but not effective with regard to time to progression and overall survival.     

Percutaneous transperineal placement of gold 198 seeds for treatment of carcinoma of the prostate

Thirty-one patients have been treated for carcinoma of the prostate with 198Au seeds placed transperineally using transrectal ultrasonic guidance. Twenty patients have been followed postoperatively for periods ranging from 3 to 31 months, with an average follow-up time of 12 months. Cumulative dose of radiation to the prostate calculated by dosimetry was either 9,000 rads or 15,000 rads. Serial transrectal ultrasound examinations performed on these patients showed a decrease in prostate size in all patients within 6 months of treatment, with a statistically significant decrease observed between the third and sixth months. No significant difference in amount or rate of tumor regression was noted when tumor stage and grade were correlated to volume decrease after treatment. Patients who received the larger doses of radiation (15,000 rads) showed a significantly greater rate of decline in prostatic volume than those who received 9,000 rads. Seven patients underwent prostate biopsy between 12 and 18 months after treatment; six biopsies showed residual tumor. Complications after treatment included urinary retention because of prostatic edema (three), radiation urethritis (three), and rectal ulceration (one). Transperineal placement of 198Au is well tolerated and offers an alternative to external beam radiation for treatment of carcinoma of the prostate.     

Retrospective analysis of 74 cases of seminoma treated with radiotherapy

BACKGROUND: Standard post-orchiectomy radiotherapy (RT) is accepted as a standard management option for stage I seminoma. METHODS: Retrospective evaluation of 74 patients with stage I seminoma was performed according to the Royal Marsden staging system. All of the patients underwent RT in the Radiation Oncology Department of Gülhane Military Medical Academy between 1974 and 1995. The median age of patients was 27 years (range, 20-56). Radiotherapy was applied to all of the patients after orchiectomy for adjuvant purposes. Sixty-nine patients underwent RT while five patients who had recurrence received chemotherapy following radiotherapy. RESULTS: After a mean follow-up period of 54 months, the 5-year overall survival rate was 98.61%, which complied with the literature. The disease-free survival rate was 90.54%. According to the World Health Organization toxicity scale, acute enteritis was 9.4% for grade I and 5.4% for grade II, while nausea/vomiting was 36.4% for grade I and 5.4% for grade II. CONCLUSION: To avoid acute toxicity related to RT, prognostic risk factors should be well-known and patients with low risk factors should be monitored carefully after orchiectomy. RT should be directed to the para-aortic +/- ipsilateral pelvic lymph nodes in high risk patients. Although post-orchiectomy RT is a traditional management option for clinical stage I seminoma, the results of RT should be well-known to compare it with other treatment options (e.g. RPLND, adjuvant chemotherapy and surveillance).     

High-dose radiation-induced meningiomas in elderly

The authors report 2 cases of cerebral meningiomas following high-dose radiotherapy in elderly patients treated for skull basaloma. These two are the first cases over 65 years old cases reported in the literature.The pathological and clinical characteristics of high-dose radio-induced meningiomas are the following: 1) children appear particularly sensitive to the development of this tumor; 2) there is a female patient predominance, in contrast to the male dominance observed in low-dose meningioma, 3) these tumors present a peak frequency in third decade of life; 4) frequentely, these tumors are atypical and recur.     

Accuracy of a multidisciplinary team-led discussion in predicting postmastectomy radiotherapy

Introduction

Immediate breast reconstruction (IBR) is performed increasingly following mastectomy for breast cancer. The literature suggests higher reconstructive failure and poorer cosmesis in the subgroup of patients receiving postmastectomy radiotherapy (PMRT) following IBR. We set out to determine the accuracy of a multidisciplinary team (MDT) discussion in predicting PMRT.

Methods

Preoperative MDT discussions were recorded prospectively over a 12-month period (from February 2011) in a symptomatic breast unit. The estimated need for PMRT was stratified into ‘PMRT not required’, ‘PMRT possibly required’, ‘PMRT probably required’ and ‘PMRT required’ groups.

Results

Of 156 referrals included in the study, 76 patients (49%) underwent mastectomy: 61 simple mastectomy, 10 skin sparing mastectomy (SSM) and delayed-immediate breast reconstruction, 3 SSM and implant-based IBR, and 2 mastectomy IBR with an autologous flap. The IBR rate was therefore 19.7%. The proportion of patients who received PMRT was 14% (3/21) in the ‘PMRT not required’, 30% (7/23) in the ‘PMRT possibly required’, 65% (9/14) in the ‘PMRT probably required’ and 94% (17/18) in the ‘PMRT required’ groups. Assigning a linear numerical score (1–4) to these groups (higher score representing greater likelihood of receiving PMRT), the predicted need for PMRT correlated with the proportion of patients who ultimately received PMRT (linear regression r²=0.98, p=0.01).

Conclusions

This study has examined the factors influencing MDT discussions regarding IBR, demonstrating that the MDT is reasonably accurate at predicting need for PMRT. Whether such accuracy is clinically adequate and/or reproducible across units is debatable.     

Intraoperative radiotherapy for resectable and unresectable pancreatic carcinoma

Eighty patients with pancreatic carcinoma were treated by intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of 111 patients treated by surgery alone. For resectable patients, the radiation dose was 30 Gy and the average field sizes were 8 or 10 cm; for unresectable patients, these values were 20–30 Gy and 6 or 8 cm, respectively. No side effects of IORT were observed. In 49 resectable stage III patients, the IORT group (n=16) had a higher survival rate than the non-IORT group (n=33); i.e., 1-year survival rates of 44.6% vs 23% and 2-year survival rates of 37.2% vs 7.7% after surgery (P<0.05). However, there was no significant difference in survival rate between the IORT group (n=28) and the non-IORT group (n=29) in 57 resectable patients in stage IV. In unresectable patients, the IORT group (n=31) (P<0.05) had a higher survival rate than the non-IORT group (n=38) (P<0.05). The palliative effect of IORT on abdominal or back pain was evaluated in 15 patients who had such symptoms and did not undergo tumor resection. Overall, pain decreased or disappeared in 13 of these patients (87%). Offprint requests to: A. Nakao     

Radical versus postoperative radiotherapy for localized prostate cancer: a 10-year experience of an academic hospital

This study is a presentation of our department’s experience in the treatment of localized prostate cancer with either radical or postoperative radiotherapy (RT). Fifty-five patients with clinical localized prostate cancer were reviewed. Thirty-three patients (T1-T2AN0M0 stage) were treated with radical RT and 22 (T2B-T3N0M0 stage) with postoperative RT. All patients received hormonal therapy. Primary end points of the study were the incidence of clinical and biochemical recurrences and death in the whole group and according to treatment modality. Within a median follow-up of 18 months the overall incidence of clinical relapse was 16.9%, of biochemical relapse 12.7% and of death 10.9%. Both treatment options achieved similar outcomes despite the fact that the patients in the postoperative RT group were of higher stage. Radical RT group tended to have better overall and disease-free survival compared to postoperative RT group, but there was no statistically significant evidence. Long-term toxicity was negligible.     

Stereotactic radiotherapy in metastatic breast cancer

The treatment of metastatic breast cancer is largely focused on systemic therapy. However, over the past decades, there has been growing interest in the use of metastasis-directed therapy in selected cases presenting with an oligometastatic phenotype, i.e. low disease burden with a more indolent biology. Identification of the oligometastatic breast cancer population has, so far, proven elusive. Stereotactic radiotherapy offers an effective, non-invasive approach to ablate metastatic disease both in the brain and in extra-cranial settings. The advent of advanced imaging techniques for target definition, along with the ability to achieve highly conformal dose deposition with steep dose fall-off, enable safe implementation of extreme hypofractionated and single fraction regimens with ablative intent. There is growing evidence that radiation-based treatments are more cost-effective when compared to other ablative modalities. This article provides preliminary evidence that metastasis-direct ablation, with advanced radiotherapy techniques, may play an important role in the management of metastatic breast cancer patients, potentially improving clinical outcomes with minimal toxicity. However, prospective randomized controlled trials are needed to further the understanding of the interaction between systemic therapy and ablative irradiation. Additionally, research in genomic and molecular profiling is needed to characterize metastatic breast cancer patients who will most likely benefit from such combined treatment approaches.     

Surgery for local recurrence of rectal cancer

OBJECTIVE: Despite improvement in management of primary rectal cancer, 2.6-32% of patients develop local recurrence. A proportion of these patients can be amenable to salvage surgery. The present article reviews the evidence for and against the surgical management for local recurrence of rectal cancer, the role of adjuvant and intraoperative radiotherapy (IORT), and evaluates short and long-term outcomes. METHOD: A literature search was performed using Medline, Embase, Ovid and Cochrane database for studies between 1980 and 2005 assessing surgical management of local recurrence of rectal cancer and the evidence was critically evaluated. RESULTS: Nearly 50% of rectal cancer recurrences are local and are therefore potentially amenable to curative resection. Preoperative imaging is important for appropriate selection of patients for surgery and preoperative adjuvant therapy is essential. Five-year survival following resection ranges from 18% to 58% with 5-year survival following complete resection of over 35% though morbidity ranges from 21% to 82%. Neoadjuvant radiotherapy is beneficial and IORT may have a contributory role in treatment. Aggressive surgical treatment favourably affects quality of life and is cost effective. Surgery for local recurrence can result in significant long-term survival with acceptable morbidity and improved quality of life in appropriately selected patients. Assessment in a specialist centre familiar with these techniques is essential.     

Principles of cancer treatment by radiotherapy

Radiotherapy (or radiation therapy) uses ionizing radiation to selectively kill cancer cells, especially for solid tumours. Like surgery, it is meant to be a ‘local’ treatment, although its beneficial systemic effects are being discovered. It is most commonly used in addition to surgery (adjuvant, e.g. breast), but its role in the neoadjuvant setting in combination with chemotherapy for some cancers (e.g. rectum) is also established. In early stages of cancer, it can be the definitive treatment, avoiding surgery and enabling organ preservation (e.g. larynx), while in late stages, it can provide excellent palliation (e.g. bone metastasis). Radiotherapy can be delivered at various energy levels (kiloVolts, megaVolts), with various subatomic particles (e.g. electrons, protons, and high-energy electromagnetic radiation). The traditional bulky equipment (e.g. linear accelerator) needs to be housed in an underground bunker and uses complex imaging to improve precision and avoid radiation to normal tissues. Fractionated regimens spanning several days reduce individual doses. Modern techniques using mobile devices (e.g. TARGIT-IORT) can deliver radiotherapy during surgery with the highest precision and immediacy.     

Conformal high dose rate brachytherapy improves biochemical control and cause specific survival in patients with prostate cancer and poor prognostic factors

PURPOSE: To improve outcome for patients with prostate cancer with poor prognostic factors higher than conventional radiation doses are required. To achieve this outcome a brachytherapy boost was given. We report the results of the first high dose rate dose-escalation brachytherapy trial. MATERIALS AND METHODS: Between 1991 and 2000, 207 patients were prospectively enrolled in a dose escalation trial including pelvic radiotherapy and conformal high dose rate prostate brachytherapy boost. The dose was increased from 5.5 to 11.5 Gy. per implant. Patient eligibility for the study included pretreatment prostate specific antigen 10 or greater, Gleason 7 or greater or clinical stage T2b or higher. No patient received hormonal therapy. The American Society for Therapeutic Radiology and Oncology consensus panel definition of biochemical failure was applied. RESULTS: Median patient age was 69 years. Mean followup was 4.7 years (range 0.6 to 10.4). The 5-year actuarial biochemical control rate was 74%. The 5-year biochemical control was 85% for 1 poor prognostic factor, 75% for 2 and 50% for all 3 (p = 0.001). On Cox regression multivariate analysis lower brachytherapy dose, and higher Gleason and nadir value were associated with biochemical failure. The 5-year actuarial overall survival was 92%, cause specific survival 98% and disease-free survival 68%. The 5-year actuarial rates of complications were 8% and 0% for grades 3 and 4 genitourinary, and 0.5% and 0.5% for grades 3 and 4 gastrointestinal, respectively. The 5-year actuarial impotence rate was 51%. CONCLUSIONS: For patients with poor prognostic factors external beam radiation therapy with conformal high dose rate brachytherapy boost improved biochemical control, resulting in a high cause specific survival rate with low toxicity. Another important advantage is that the patient is not radioactive after the high dose rate implant.