Full-dose intraoperative radiotherapy with electrons during breast-conserving surgery

HYPOTHESIS: The current standard treatment for early breast cancer includes conservative surgery followed by entire breast radiotherapy (RT). Recent study findings show that most local recurrences are in the scar tissue area suggesting that whole-breast RT may not always be necessary. If the volume of breast tissue to be irradiated is limited, RT may be performed intraoperatively. Intraoperative RT delivered with electrons at the total isodose of 2100 rad (21 Gy) could in principle substitute the currently used radiation course of external RT after breast-conserving surgery in selected cases. PATIENTS AND METHODS: We report our findings on intraoperative RT using a specially designed mobile linear accelerator delivering 4 energy levels of electrons (3, 5, 7, and 9 MeV) via a head maneuvered by a robot arm. We applied this technique to 237 patients with breast cancer (mean age, 59 years; age range, 33-80 years) with tumors smaller than 2 cm in maximum diameter (T1); most underwent wide resection and an axillary sentinel node biopsy. RESULTS: After a median follow-up of 19 months (range, 7-33 months), the rate of posttreatment complications is very low. Four patients (1.7%) developed breast fibrosis-mild in 3 patients and severe in 1 patient-that resolved in 24 months. Three patients (1.4%) developed ipsilateral breast cancer-2 (1.0%) contralateral breast cancer, 1 (0.5%) supraclavicular node metastasis, and 1 (0.5%) distant metastases. CONCLUSIONS: Intraoperative RT with electron beams reduces irradiation to the skin, subcutaneous tissue, and contralateral breast and lung. It appears to be a promising method for irradiating conservatively treated breasts and it avoids the long period of postoperative RT that may not be easily accessible to all patients.     

Full-dose intraoperative radiotherapy with electrons during breast-conserving surgery: experience with 590 cases

BACKGROUND: Previous studies show that local recurrences after breast-conserving treatment occur in the site of the primary tumor. The need for postoperative radiotherapy on the whole breast is challenged in favor of radiotherapy limited to the area of the breast at high risk of recurrence. The new mobile linear accelerators easily moved close to the operating table to allow the full-dose irradiation during surgery. PATIENTS AND METHODS: From July 1999 to December 2003, 590 patients affected by unifocal breast carcinoma up to a diameter of 2.5 cm received wide resection of the breast followed by intraoperative radiotherapy with electrons (ELIOT). Most patients received 21 Gy intraoperatively, biologically equivalent to 58 to 60 Gy in standard fractionation. Patients were evaluated 1, 3, 6, and 12 months after surgery, and thereafter every 6 months, to look for early, intermediate, late complications, and other events. RESULTS: After a follow-up from 4 to 57 months (mean, 24 months; median, 20 months), 19 patients (3.2%) developed breast fibrosis, mild in 18, severe in 1, which resolved within 24 months. Three patients (0.5%) developed local recurrences, 3 patients ipsilateral carcinomas in other quadrants and other 5 patients contralateral breast carcinoma. One patient (0.2%) died of distant metastases. CONCLUSIONS: ELIOT is a safe method for treating conservatively operated breasts, avoids the long period of postoperative radiotherapy, and reduces drastically the cost of radiotherapy. ELIOT reduces radiation to normal tissues and organs. Results on short-term and middle-term toxicity up to 5 years of follow-up are good. Data on local control are encouraging.     

术中光子线与术后外照射在早期乳腺癌保留乳房手术瘤床加量放疗中的近期疗效比较

目的比较早期乳腺癌保乳术后采用术中光子线对比术后外照射瘤床加量的安全性和可行性。 方法回顾性分析2014年12月至2018年6月中山大学附属第一医院甲状腺乳腺外科收治的222例早期乳腺行保乳手术患者的临床资料,其中72例采用术中光子线瘤床加量（术中放疗组）,150例采用术后外照射瘤床加量（术后放疗组）。所有患者术后均行全乳±淋巴引流区外照射放疗,50 Gy/25 Fr。观察术后两组患者的不良反应、美容效果及近期疗效。 结果中位随访35个月（11~52个月）,术中放疗组比术后放疗组有更低的乳腺纤维化发生率（2.8% vs 13.3%,χ²=6.071,P=0.014）,但术后血肿的发生率更高（5.6% vs 0,P=0.015）。术后感染、坏死而引起切口延迟愈合、照射野内中度以上的乳腺疼痛,在两组间差异无统计学意义。术中放疗组和术后放疗组总体不良反应的发生率分别为13.9%和16.0%,美容效果优良率分别为83.3%（60/72）和89.3%（134/150）,术后3年的局部复发率分别为0（0/72）和1.3%（2/150）,差异均无统计学意义。 结论与术后外照射瘤床加量相比较,早期乳腺癌保乳术采用术中光子线的不良反应、美容效果和近期疗效相似。     

Treatment of gastric cancer with combined surgery and intraoperative radiotherapy

In order to increase the cure rate of stomach cancer, we have used intraoperative radiotherapy in which resectable lesions are removed surgically and the remaining cancer nests sterilized with a single massive dose of irradiation during laparotomy. In cooperation with surgeons, radiologists, and anesthesiologists, effective doses of irradiation of 3,000–4,000 rads were administered in 85 patients with advanced cancer. After resection of the stomach and removal of regional lymph nodes, and before gastrojejunostomy, the region of the celiac axis was irradiated in order to destroy regional microscopic metastasis that could not be removed surgically. The survival rates were 0 of 8 patients with nonresectable lesions, 3 of 15 with absolutely noncurable resectable tumors, 6 of 11 with relatively noncurable resectable cancers, and 48 of 51 with absolutely or relatively curable resectable lesions. In the latter group, insufficient time has elapsed to calculate the 5-year survival rate. No serious complications occurred except for an increase of serum amylase. These results, as well as experimental radiotherapy of the dog pancreas, are discussed.

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Résumé Pour accroître les chances de guérison du cancer gastrique, nous avons utilisé une radiothérapie peropératoire avec exérèse chirurgicale des lésions résécables et stérilisation des foyers cancéreux résiduels par une seule dose massive d'irradiation pendant la laparotomie. Dans ce travail de coopération entre chirurgiens, radiothérapeutes et anesthésistes, des doses effectives de 3,000–4,000 rads ont été administrées à 85 malades atteints de cancer avancé. L'estomac et les ganglions régionaux sont réséqués et, avant de réaliser la gastrojéjunostomie, la région du trépied coeliaque est irradiée pour détruire les métastases régionales microscopiques qui ne peuvent être excisées. Les survies ont été de 0 cas sur 8 lésions non résécables, de 3/15 tumeurs résécables mais absolument incurables, de 6/11 cancers résécables et relativement incurables et de 48/51 lésions résécables et certainement ou relativement curables. Pour ce dernier groupe, le follow-up est insuffisant pour calculer les survies de 5 ans. Nous n'avons observé aucune complication grave sauf une élévation de l'amylasémie. Ces résultats sont discutés ainsi qu'une étude expérimentale d'irradiation du pancréas chez le chien.

     

Results of posterior surgery with intraoperative radiotherapy for spinal metastases

Object: Spinal cord compression from spinal metastasis represents a substantial clinical problem. Complete resection of spinal metastases is difficult in many cases, and conventional surgical decompression of the spinal cord with or without instrumentation often results in unsatisfactory neurological recovery and local recurrence, even if combined with external radiotherapy. To increase rates of local control and improve neurological recovery in such cases, we introduced decompressive surgery combined with intraoperative radiotherapy (IORT) for the treatment of spinal metastasis in 1992. We report the results of neurological recovery and local control in cases that received surgery with IORT. Methods: Between November 1992 and December 2001, 133 cases (117 patients) were treated using IORT at Tokyo Metropolitan Komagome Hospital. The 79 cases (74 patients) that received posterior spine surgery only for spinal paresis due to spinal metastasis were reviewed. Results: Improvement of at least one level according to Frankels classification was attained in 68 cases (86%). Of the 58 patients unable to walk preoperatively, 45 patients (78%) regained walking ability postoperatively. Rate of local recurrence was 2.5%. Conclusions: IORT, combined with posterior surgery and FERT, might be one of the effective methods for local control of spinal metastasis and neurological improvement, especially in cases with progressive and multi-level lesions.     

Micro-invasive surgery combined with intraoperative radiotherapy for the treatment of spinal metastasis

Purpose

This is a retrospective analysis of the strategy and clinical results of surgery combined with intraoperative radiotherapy (IORT) to treat spinal metastases.

Methods

We delivered tumour-conformal IORT in 40 patients with 52 metastatic vertebrae based on our surgical classification system. The strategies were evaluated with respect to neurologic function and spinal stability. The EORTC QLQ-BM22, visual analogue scale (VAS) and the Frankel Scale were used to assess quality of life, pain and neurologic function. Local control was evaluated every 3 months using X-rays and MRI.

Results

Micro-invasive IORT was performed in 42 vertebrae (80.8%), and open surgery with IORT was performed in 10 vertebrae (19.2%). Single-level, 2-level and 3-level IORT was performed in 30, 8 and 2 cases, respectively. The delivered dose was 9.2 ± 3.6 Gy (8–15 Gy) with a depth of 10.1 ± 2.1 mm. The actual IORT treatment time was 5 min and 16 s. The follow-up period was 6–23 months (mean: 12.5 months). The local control rate was 92.3%. The EORTC QLQ-BM22 scores showed that patients had significant improvements in pain location, degree and function after treatment (P < 0.01). Thirty-five patients (89.7%) achieved pain relief throughout the follow-up period. VAS scores were significantly reduced by 3.4 points 3 months after treatment. Neurological function was improved in 7 patients (87.5%). No radiation-related complications were observed.

Conclusions

Surgery combined with tumour-conformal IORT can effectively relieve pain, achieve good local control and improve QOL.

     

The role of intraoperative radiotherapy in oncological pediatric surgery

Conventional external beam radiation has proved its profit in pediatric tumors; but its complications have limited it in therapeutical approach. Intraoperative radiotherapy delivers a high single dose in residual tumor or high risk areas during surgery. In our center, during last two years, 7 patients have been candidates to surgery with intraoperative radiotherapy (the age range was between 5 months-17 years; mean 8.5 years). Two patients were excluded of our protocol because of their intraoperative stage. Patients tumors types were: neuroblastoma (n = 3; stage III and IV), soft tissue sarcomas (n = 1) and Ewing's sarcoma (n = 1). The radiation doses ranged from 500 cGyto-1200 cGy. Local control tumor was achieved in 4 patients and no-complications were present secondary to surgery or intraoperative radiotherapy. Intraoperative radiotherapy seems to be a feasible treatment which might promote local control in pediatric tumors with protection of normal tissues and could be an excellent complement in special cases.     

Persistent pain after targeted intraoperative radiotherapy (TARGIT) or external breast radiotherapy for breast cancer: a randomized trial

Persistent pain after breast cancer treatment (PPBCT) affects between 25 and 60% of patients depending on surgical and adjuvant treatment. External breast radiotherapy (EBRT) has been shown to be a riskfactor for PPBCT, raising the question whether intraoperative radiation therapy (IORT), with its smaller radiation field may reduce the development of PPBCT. Using data from the TARGIT-A trial, the aim of this study was to compare these two treatments with regard to development of PPBCT. A total of 281 patients enrolled in the TARGIT-A trial from the Copenhagen University Hospitals was screened for participation, and a total of 244 patients were included and received a detailed questionnaire. The response rate was 98%, leaving 238 patients for the final analysis. Pain prevalence were 33.9% in the EBRT group and 24.6% in the IORT group (p = 0.11). Treatment with IORT may not alter the risk of PPBCT.     

Rationale and indications for limited surgery in breast cancer: Current data

A limited number of clinical trials have been performed in the last 20 years to test the validity of techniques for preserving the breast in patients with a mammary carcinoma. From the trials published, a number of conclusions can be formulated: (a) quadrantectomy, axillary dissection, and radiotherapy for small tumors is a procedure as safe as the Halsted mastectomy in terms of local, regional, and distant recurrences, and long-term survival (Milan trial, Villejuif trial); (b) limited resection plus axillary dissection without radiotherapy exposes the patients to a high risk of local recurrences (NSABP trial); and (c) large resection without axillary dissection and with inadequate radiotherapy will increase the risk of axillary recurrences (Guy's Hospital trial). Whether the increase of local/regional recurrences will decrease the long-term survival rates (Guy's Hospital) or will not influence the survival (NSABP) must be clarified. The main problems to be faced by future trials are: the extent of the surgical act (limited excision versus extensive resection, axillary dissection versus no dissection, total axillary dissection versus axillary sampling), the type of radiotherapy (immediate versus delayed, whole breast versus limited direct field, boost versus no boost, regional nodes irradiation versus no nodal irradiation), the comparison with other forms of surgery providing good cosmetic results (conservative treatments versus total mastectomy plus immediate reconstruction), the size of primary tumor to be submitted to conservation procedures, and the pathologic patterns requiring differentiated conservative technique (lobular carcinoma in situ, intraductal noninfiltrating carcinoma, Paget's disease, and minimal carcinoma).

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Resumen Un limitado numéro de ensayos clínicos ha sido realizado en los últimos 20 años para comprobar la validez de las técnicas de preservación del seno en pacientes con carcinoma mamario. Con base en los informes publicados se pueden formular las siguientes conclusiones: (a) la cuadrantectomía, disección axilar, y radioterapia realizadas para tumores pequeños representan un enfoque tan eficaz como la mastectomía de Halsted en cuanto a recurrencia local, regional, y distal, y supervivencia a largo plazo (Milán, Villejuif); (b) la resección limitada con disección axilar pero sin radioterapia expone al paciente a un mayor riesgo de recurrencia local (NSABP); y (c) la resección amplia sin disección axilar y con radioterapia inadecuada aumenta el riesgo de recurrencia axilar (Guy's Hospital). Todavía está por aclarar si el aumento en la tasa de recurrencia local disminuye las tasas de supervivencia a largo plazo (Guy's Hospital) o si, por el contrario, no tiene influencia sobre la supervivencia (NSABP).Los principales problemas que deben resolver futures ensayos clínicos son: la extensión de la resección quirúrgica (resección limitada versus resección amplia, disección axilar versus no disección, disección axilar total versus muestreo axilar), el tipo de radioterapia (inmediata versus tardía, irradiación total del seno versus campo directo limitado, boost versus no boost, irradiación ganglionar regional versus no irradiación ganglionar), la comparación con otras formas de cirugía que dan buenos resultados estéticos (procedimientos conservadores versus mastectomía total con reconstrucción inmediata), el tamaño del tumor primario que pueda ser susceptible de operación conservadora, y los patrones histopatológicos que requieren técnicas conservadoras diferenciales (carcinoma lobular in situ, carcinoma intraductal no infiltrante, enfermedad de Paget, carcinoma mínimo).

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Résumé Un nombre limité d'essais cliniques a été tenté au cours des 20 dernières années pour apprécier la valeur de la technique conservant le sein chez les malades atteintes d'un cancer mammaire. De ces essais ont pu être tirées de nombreuses conclusions: (a) la quadrantectomie, la dissection axillaire, et la radiothérapie pour traiter les petites tumeurs représentent une méthode aussi efficace que l'opération de Halsted aussi bien en ce qui concerne les récidives locales régionales, à distance que la survie à long terme (Milan, Villejuif); (b) la résection limitée associée à la dissection axillaire mais sans radiothérapie expose à un risque élevé de récidive locale (NSABP); et (c) la résection large sans dissection axillaire et radiothérapie inadéquate augmentent les risques de récidive axillaire (Guy's Hospital). Que ces risques aillent de paire avec une diminution de la survie à long terme (Guy's Hospital) ou qu'ils soient sans influence sur la survie (NSABP) restent à démontrer.Les principaux problèmes que les futurs essais auront à résoudre se résument: dans l'extension de l'exérèse (exérèse limitée ou étendue, dissection axillaire ou pas, dissection axillaire totale ou limitée à un échantillon), dans le type de la radiothérapie (immédiate ou secondaire, étendue à tout le sein ou limitée au champ tumoral, survoletage ou non, irradiation ganglionnaire régionale ou non), dans la comparaison entre les autres formes de chirurgie susceptibles de donner de bons résultats esthétiques (traitement conservateur ou mammectome totale avec reconstruction immédiate), dans la taille de la lésion relevant des procédés conservateurs, et dans les types pathologiques nécessitant des techniques conservatrices (cancer lobulaire in-situ, cancer intraductal non infiltrant, maladie de Paget, petit cancer).

     

Outcomes of intraoperative radiotherapy for early-stage breast cancer: Experience from a multidisciplinary breast oncology program

BackgroundIntraoperative radiotherapy (IORT) was implemented at our institution for early stage breast cancer patients including those with geographic or medical co-morbidity limitations to whole breast radiation therapy (WBRT).MethodsRetrospective review of patients (n = 127) who underwent IORT from 2009 to 2016 for breast cancer. Demographics, pathology, toxicity, and recurrences were ascertained.ResultsThe median age was 67 years (interquartile range: 62–73). At median follow-up (49.6 months), 5 patients (4%) had ipsilateral breast tumor recurrence with median time to recurrence of 36.8 months. Acute and late grade ≥3 skin toxicities were observed in 3.1% and 4.7% of patients, respectively. A subset (n = 7) who received prior ipsilateral WBRT was found to have no subsequent local recurrence, one case of acute grade 3 skin toxicity, and no late toxicity.ConclusionsIORT is a safe and effective alternative to whole breast radiotherapy, and serves as a suitable alternative to completion mastectomy in locally recurrent breast cancer.     

Surgical technique of intraoperative radiotherapy in conservative treatment of limited-stage breast cancer

At the European Institute of Oncology, Milan, Italy, we have focused our interest on the use of intraoperative radiation therapy (IORT) in limited-stage breast cancer that is conservatively treated. A new technique to perform IORT was applied in 185 patients from July 1, 1999, to October 31, 2001. As the surgeon plays a crucial role in this procedure in selecting the patients, performing the breast resection, preparing the gland as a target to receive IORT, delivering the radiation directly to the mammary gland via a dedicated applicator, and, finally, reconstructing the breast, each phase of the surgical technique has been completely standardized and is described herein. The use of IORT in the conservative treatment of breast cancer could allow the course of external fractionated-dose radiation therapy to be completely avoided; IORT dramatically reduces radiation exposure of the skin, lung, and subcutaneous tissues and avoids the irradiation of the contralateral breast, which contributes to a very low incidence of radiation-induced sequelae. In our experience, IORT for limited-stage breast carcinoma is easy to perform and only briefly prolongs the duration of the surgical procedure.     

术中定向放疗推量照射在乳腺癌保乳术中临床应用研究

目的 研究乳腺癌保乳手术联合IntraBeam术中放疗系统进行术中靶向瘤床推量放射治疗的可行性、安全性、有效性及美容效果。方法 共69例早期乳腺癌保乳手术患者接受了治疗,其中18.8%（13/69）患者年龄少于45岁,52.2%（36/69）肿物大于2 cm,40.6%（28/69）组织细胞学分级3级,29.0%（20/69）病人有淋巴结转移。病人保乳术后采用IntraBeam术中放疗系统瘤床表面20 Gy剂量进行术中靶向瘤床推量放射治疗,待化疗完成（或伤口愈合后）2周后给予传统全乳外照射放射疗治疗（50 Gy,共25次,省略瘤床推量照射）,评估患者近期疗效及不良反应。结果 总共27.5%（19/69）患者出现急性并发症,2.9%（2/69）患者出现血肿,8.7%（6/69）出现血清肿,7.2%（5/69）出现切口感染,8.7%（6/69）切口愈合延迟,切口中位愈合时间3.8（1.0~11）个月,中位随访24.8个月（12~51）,2.9%（2/69）患者出现同侧乳房内复发,未出现远处转移及死亡病例,乳房美容效果评估优、良者术后1年占89.9%,术后2年占89.7%。结论 乳腺癌保乳手术联合IntraBeam术中放疗系统进行术中靶向瘤床推量放射治疗近期疗效满意、不良反应较少,由于病人数量较少,随访时间较短,长远疗效仍需要进一步的验证。     

Radiolunate arthrodesis in rheumatoid wrist--the modified Chamay technique with broadening of indications

AIM: Radiolunate arthrodesis (RLA) has become an established surgical technique for stabilising wrists destroyed by RA. Our modified surgical technique with special osteosynthesis material has enabled the spectrum of indications to be expanded to include stage IV a--sagittal instability. METHOD: 44 radiolunate arthrodeses were carried out from 10.96 to 6.98. 19 (43.2%) satisfied the criteria for correction RLA with correction of sagittal instability. All (100%) of the 19 radiolunate arthrodeses were included in a follow-up examination, and all were examined clinically and radiologically at specified intervals. The mean follow-up is 22.8 months. RESULTS: Correction of the lunate drift in the sagittal plane was successful. The radiolunate angle was reduced from a mean 23.7 degrees before surgery to 9.3 degrees afterwards. The lunate drift in the frontal plane, which is shown by the ulnar translation index (UTI) was corrected from an average of 0.35 before surgery to 0.30 afterwards. Restoration of the carpal height by bone grafting from a mean preoperative CHI of 0.47 to 0.50 after surgery was achieved. We discovered one failure, thus the consolidation rate dropped to 94.7%. CONCLUSION: Since the capitate is the centre of rotation and movement at the wrist, a stable central pivot is essential, and correction of sagittal instability is particularly important. This demand can also be met by our modified radiolunate arthrodesis.     

Prognosis after breast recurrence following conservative surgery and radiotherapy in patients with node-negative breast cancer

BACKGROUND: Breast conservation surgery with radiotherapy is a safe and effective alternative to mastectomy for early-stage breast cancer. This retrospective study examined the outcome of patients with isolated local recurrence following conservative surgery and radiotherapy in node-negative breast cancer. METHODS: Between November 1979 and December 1994, 503 women with node-negative breast cancer were treated by conservation surgery and radiotherapy without adjuvant systemic therapy. RESULTS: After a median follow-up of 73 months the 5-year rate of freedom from local recurrence was 94 per cent. Thirty-five patients developed an isolated local recurrence within the breast as a first event. Thirty-three patients were treated with salvage mastectomy and two patients were treated with systemic therapy alone. The 5-year rate of freedom from second relapse was 46 per cent and the overall 5-year survival rate was 59 per cent for patients who had salvage mastectomy. Patients who developed breast recurrence as a first event had a 3.25 greater risk of developing distant metastasis (P < 0.001) than those who did not have breast recurrence as a first event. CONCLUSION: Salvage mastectomy after local recurrence was an appropriate treatment if there was no evidence of distant metastasis. Breast recurrence after conservative surgery and radiotherapy in node-negative breast cancer predicted an increased risk of distant relapse.