Photon Radiosurgery System Research Articles

Treatment Protocols and Outcomes of Intraoperative Radiotherapy for Brain Metastases: A Systematic Review

Objectives: Intraoperative radiotherapy (IORT) is the delivery of ionizing radiation to the tumor or tumor bed during surgery. It is being explored as a treatment modality for brain metastases (BrMs). We aimed to determine the safety and efficacy of IORT for BrMs by reviewing the current evidence. Methods: We performed a systematic review of the online databases for studies on IORT for BrMs. Data on clinical features, treatment modalities, and outcomes were collected. Results: Five studies (n=179) were included. Mean age was 60.4 years, 43% were women. The most common etiology of BrMs were lung, melanoma, breast, and renal cancer. Ninety-five patients underwent IORT with the Photon Radiosurgery System (PRS) while 84 were treated with the INTRABEAM system. Follow-up ranged from 5 days to 94 months. The most frequent complication was radiation necrosis. Local recurrence and distal progression were seen in 11-77% and 0-82%, respectively. The 6- and 12-month overall survival ranged from 60-86% and 34-73%, respectively. Conclusion: The results of the systematic review on the safety and efficacy of IORT on BrMs were inconclusive, due to heterogeneity of the studies. Larger prospective studies are needed to determine the optimal dose, efficacy, and safety of IORT for BrMs.

Pre- and Intraoperative Factors Influencing Omission of Planned Intraoperative Radiation Therapy As a Boost for Breast Cancer Patients Undergoing Breast Conserving Treatment

Ongoing trials are investigating the efficacy of intraoperative radiotherapy (IORT) using photon radiosurgery system as a tumor bed boost for high-risk breast cancer patients undergoing breast conserving treatment. We evaluated preoperative and intraoperative variables influencing the decision to abort the planned IORT boost. A phase II IORT boost trial began in August 2014, and eligible patients were women who were aged 20 years or older, were compatible for lumpectomy, and had ductal carcinoma in situ (DCIS) or invasive carcinoma (Stage I-III). All patients underwent MRI evaluation and were discussed in a multidisciplinary conference for eligibility. The presence of invasive carcinoma and DCIS in resection margins were intraoperatively assessed by the frozen pathologic examination. Optically stimulated luminescence dosimeter detected radiation dose delivered to the skin during IORT. Pre- and intraoperative variables were compared between patients undergoing IORT and those whose planned IORT was cancelled due to anatomical reasons. A total of 434 patients were eligible and underwent a surgery with intension to carry out IORT between August 2014 and December 2017. IORT was cancelled in 90 patients for anatomical reasons including repeated positive margins causing large tumor cavity or total mastectomy (n = 27), insufficient cavity-skin distance (n = 14), satellite lesions causing large tumor cavity or total mastectomy (n = 12), large primary tumor or uncertain tumor margins in MRI causing large tumor cavity (n = 6), tumor cavity geometry unsuitable for IORT (n = 6), subareolar extension (n = 6), tumor abutting pectoralis muscle (n = 3), and non-anatomical reasons including patient’s refusal (n = 5), bilateral breast cancer (n = 3) or benign pathology (n = 3) confirmed during surgery, device malfunction (n = 3), and scheduling difficulty (n = 2). The percentage of IORT omission was 23.8% in 2015, 20.9% in 2016, and 19.3% in 2017. Primary tumor >2.0 cm (n = 0.033) and positive frozen section (n = 0.013) were significantly associated with omission of planned IORT, while breast size, tumor location, DCIS pathology were not. The median skin dose measured during IORT was 2.10 Gy (range, 0.33-10.89 Gy), and acute toxicity after IORT and whole breast irradiation was observed in 16% of the patients (seroma requiring repeated aspiration 13.5% and wound complication 2.7%). A successful IORT procedure depended on preoperative imaging evaluation and status of surgical margins. MRI-based patient selection allowed restriction of skin dose and tolerable acute toxicity.

Intraoperative radiotherapy in locally-advanced and recurrent rectal cancer: retrospective review of 68 cases

Background: The addition of intraoperative radiation therapy (IORT) to the multimodal treatment of locally advanced or recurrent rectal cancer may improve local control. Although electron beam IORT is the most common modality, technological advances now permit the use of photon beam IORT. However, few studies have investigated these devices in rectal cancer. Methods: Retrospective review of patients (pts) treated with surgery and IORT for stage T3-T4 rectal cancer or pelvic recurrence between December 2012 and December 2014. Patients with distant metastasis were excluded. IORT was delivered with the Intrabeam Photon Radiosurgery System (PRS). The study sample included 68 pts (41 males, 27 females) ranging in age from 33 to 82 (median, 67) years. Most patients (47) had stage II primary rectal cancer (PRC), while 21 pts had stage III disease. Nine of this pts presented recurrent rectal cancer (RRC). Wanebo staging for the nine PRC cases was: Tr3 (6 pts), Tr4 (2 pts), and Tr5 (1 pt). A dose of 5.07 Gy was prescribed to a depth of 1 cm (surface dose range was 9.4-17.0 Gy; median, 14.8 Gy). Median duration of IORT was 31.9 (range, 15-36) minutes. The spherical applicator was 5 cm in diameter in 61 cases and 4.5 in seven cases. A subgroup analysis (23 pts) was performed to assess those patients with the longest follow-up (range, 17-28 minutes; median, 20.7 minutes). Of these, 18/23 (78%) received adjuvant chemotherapy. Overall survival (OS) and disease-free survival were calculated with the Kaplan-Meier method. Results: In 18 of the 68 pts (26.4%), the tumour was attached to the sidewall. Margins were positive in 7 pts (10.3%). In the 23 pts subgroup with long-term follow-up, OS was 87.0%. Local recurrence occurred in 3 of 23 pts (13%). Four cases (17.4%) of distant metastasis (lung: 3 cases; liver: 1 case) were recorded. No intraoperative complications attributable to IORT were registered. Median postsurgical discharge time was 17.7 (range, 9-25) days. No cases of hydronephrosis or ureter fibrosis after IORT were documented. Conclusions: Intrabeam PRS appears to be a safe technique for delivering IORT in rectal cancer patients. Although operating time increased slightly, outcomes in terms of toxicity, local recurrence, and survival were all quite good in comparison with other IORT delivery methods.

Intraoperative radiation therapy with the photon radiosurgery system in locally advanced and recurrent rectal cancer: retrospective review of the Cleveland clinic experience

BackgroundPatients with locally advanced or recurrent rectal cancer often require multimodality treatment. Intraoperative radiation therapy (IORT) is a focal approach which aims to improve local control.MethodsWe retrospectively reviewed 42 patients treated with IORT following definitive resection of a locally advanced or recurrent rectal cancer from 2000–2009. All patients were treated with the Intrabeam® Photon Radiosurgery System (PRS). A dose of 5 Gy was prescribed to a depth of 1 cm (surface dose range: 13.4-23.1, median: 14.4 Gy). Median survival times were calculated using Kaplan-Meier analysis.ResultsOf 42 patients, 32 had recurrent disease (76%) while 10 had locally advanced disease (24%). Eighteen patients (43%) had tumors fixed to the sidewall. Margins were positive in 19 patients (45%). Median follow-up after IORT was 22 months (range 0.2-101). Median survival time after IORT was 34 months. The 3-year overall survival rate was 49% (43% for recurrent and 65% for locally advanced patients). Local recurrence was evaluable in 34 patients, of whom 32% failed. The 1-year local recurrence rate was 16%. Distant metastasis was evaluable in 30 patients, of whom 60% failed. The 1-year distant metastasis rate was 32%. No intraoperative complications were attributed to IORT. Median duration of IORT was 35 minutes (range: 14–39). Median discharge time after surgery was 7 days (range: 2–59). Hydronephrosis after IORT occurred in 10 patients (24%), 7 of whom had documented concomitant disease recurrence.ConclusionsThe Intrabeam® PRS appears to be a safe technique for delivering IORT in rectal cancer patients. IORT with PRS marginally increased operative time, and did not appear to prolong hospitalization. Our rates of long-term toxicity, local recurrence, and survival rates compare favorably with published reports of IORT delivery with other methods.

P257 A 7-year experience of targeted intra-operative radiation therapy (TARGIT) using PRS400 photon radiosurgery system (intrabeam) for breast cancer

P257 A 7-year experience of targeted intra-operative radiation therapy (TARGIT) using PRS400 photon radiosurgery system (intrabeam) for breast cancer

Stereotactic Interstitial Radiosurgery With the Photon Radiosurgery System (PRS) for Metastatic Brain Tumors: A Prospective Single-Center Clinical Trial

To evaluate the efficacy and the treatment outcome of tumor patients being treated stereotactically with a miniature X-ray generator (Photon Radiosurgery System, PRS). Thirty-five patients with histologically diagnosed cerebral metastases were treated with a single fraction of stereotactic interstitial irradiation (median, 18 Gy). Clinical and neuroimaging evaluation were assessed at 2-, 6-, and 12-week intervals postoperatively and every 3 months thereafter. Survival, local control, and distant and overall brain freedom from progression were obtained using the Kaplan-Meier method. Median survival was 7.37 months and the actuarial survival rates at 6 and 12 months were 60.0% and 34.3%, respectively. Acute complications on six patients were associated with shorter survival. Local tumor control at the initial stage and at the last follow-up were 82% and 50%. Eighteen patients (53%) developed distant brain metastases after treatment. At 1 year, the local control rate and distant and overall brain freedom from progression were 33.0%, 43.3%, and 14.7%, respectively. A shorter local tumor control was observed by PRS treatment of a recurrent tumor and by irregular tumor configuration. Interstitial radiosurgery with the PRS requires continued investigation. It allows for an immediate and potentially cost-efficient treatment for patients with singular, small (<or= 6.36 cm(3); or <or= 2.3 cm) spherical brain metastasis subsequent to a stereotactic biopsy.

Perspective on breast and axilla preservation after introduction of targeted intraoperative radiotherapy and sentinel node biopsy for the treatment of patients with early breast carcinoma

The principal objective of the targeted intraoperative radiation therapy trial was to determine whether single-fraction intraoperative radiotherapy (IORT) targeted to the tumor bed provides equivalent local control compared with whole-breast irradiation in patients with early-stage invasive breast cancer.Patients were randomized equally to IORT versus whole breast irradiation. Patients randomized to IORT received tumor bed irradiation prescribed at 20 Gy to the surgical margins using soft x-rays (50 kV) delivered with the Intrabeam Photon Radiosurgery System (Zeiss Inc, Oberkochen, Germany). Patients randomized to whole-breast irradiation received radiotherapy postoperatively. Prior wide local excision was allowed. Patients randomized to IORT after initial breast-conserving surgery received IORT at a second operation.A total of 779 patients were accrued at 16 institutions internationally. Five hundred sixty patients were randomized before initial breast-conserving surgery. One hundred eighty-three patients were randomized after initial breast-conserving surgery. The median follow-up time was 359 days.Targeted IORT allowed the entire dose of radiotherapy to be administered in a single fraction at the time of breast-conserving surgery, thus avoiding the need for repeated radiotherapy treatments or placement of indwelling radiotherapy devices.

The TARGIT trial: targeted intraoperative radiation therapy versus conventional postoperative whole-breast radiotherapy after breast-conserving surgery for the management of early-stage invasive breast cancer (a trial update)

Background The principal objective of the targeted intraoperative radiation therapy trial was to determine whether single-fraction intraoperative radiotherapy (IORT) targeted to the tumor bed provides equivalent local control compared with whole-breast irradiation in patients with early-stage invasive breast cancer. Methods Patients were randomized equally to IORT versus whole breast irradiation. Patients randomized to IORT received tumor bed irradiation prescribed at 20 Gy to the surgical margins using soft x-rays (50 kV) delivered with the Intrabeam Photon Radiosurgery System (Zeiss Inc, Oberkochen, Germany). Patients randomized to whole-breast irradiation received radiotherapy postoperatively. Prior wide local excision was allowed. Patients randomized to IORT after initial breast-conserving surgery received IORT at a second operation. Results A total of 779 patients were accrued at 16 institutions internationally. Five hundred sixty patients were randomized before initial breast-conserving surgery. One hundred eighty-three patients were randomized after initial breast-conserving surgery. The median follow-up time was 359 days. Conclusion Targeted IORT allowed the entire dose of radiotherapy to be administered in a single fraction at the time of breast-conserving surgery, thus avoiding the need for repeated radiotherapy treatments or placement of indwelling radiotherapy devices.

Intraoperative radiotherapy (IORT) with photon radiosurgery system (PRS) combined with postoperative external beam radiotherapy (ebrt) in patients with early oral cancer. Preliminary results on treatment tolerance and utility

Intraoperative radiotherapy (IORT) with photon radiosurgery system (PRS) combined with postoperative external beam radiotherapy (ebrt) in patients with early oral cancer. Preliminary results on treatment tolerance and utility

Phase I study of intraoperative radiotherapy with photon radiosurgery system in children with recurrent brain tumors: Preliminary report of first dose level (10 Gy)

To describe the preliminary results after intraoperative radiotherapy (IORT) with the photon radiosurgery system in children with recurrent brain tumors treated at the first dose level (10 Gy) of a Phase I protocol. A Phase I IORT dose escalation protocol was initiated at Children's Memorial Hospital to determine the maximal tolerated IORT dose in children with recurrent brain tumors. Fourteen children have received IORT thus far. Eight had been previously irradiated. Thirteen children had ependymoma. The median follow-up was 16 months. Three patients (21%) developed radiation necrosis on follow-up MRI scans 6 to 12 months after IORT. They had not been previously irradiated and had received 10 Gy to a depth of 5 mm. One required surgery and the other two had resolution of their lesions without treatment. All 3 patients were asymptomatic at the last follow-up. No other late toxicity was observed at the last follow-up visit. Eight patients (57%) had tumor control within the surgical bed after IORT. Our findings have demonstrated the safety and feasibility of IORT to a dose of 10 Gy to 2 mm in children with previously irradiated brain tumors. IORT to a dose of 10 Gy at 5 mm was associated with a greater complication rate.

Stereotactic interstitial radiosurgery for cerebral metastases

The Photon Radiosurgery System (PRS) is a miniature x-ray generator that can stereotactically irradiate intracranial tumors by using low-energy photons. Treatment with the PRS typically occurs in conjunction with stereotactic biopsy, thereby providing diagnosis and treatment in one procedure. The authors review the treatment of patients with brain metastases with the aid of the PRS and discuss the indications, advantages, and limitations of this technique. Clinical characteristics, treatment parameters, neuroimaging-confirmed outcome, and survival were reviewed in all patients with histologically verified brain metastases who were treated with the PRS at the Massachusetts General Hospital between December 1992 and November 2000. Local control of lesions was defined as either stabilization or diminution in the size of the treated tumor as confirmed by Gd-enhanced magnetic resonance imaging. Between December 1992 and November 2000, 72 intracranial metastatic lesions in 60 patients were treated with the PRS. Primary tumors included lung (33 patients), melanoma (15 patients), renal cell (five patients), breast (two patients), esophageal (two patients), colon (one patient), and Merkle cell (one patient) cancers, and malignant fibrous histiocytoma (one patient). Supratentorial metastases were distributed throughout the cerebrum, with only one cerebellar metastasis. The lesions ranged in diameter from 6 to 40 mm and were treated with a minimal peripheral dose of 16 Gy (range 10-20 Gy). At the last follow-up examination (median 6 months), local disease control had been achieved in 48 (81%) of 59 tumors. An actuarial analysis demonstrated that the survival rates at 6 and 12 months were 63 and 34%, respectively. Patients with a single brain metastasis survived a mean of 11 months. Complications included four patients with postoperative seizures, three with symptomatic cerebral edema, two with hemorrhagic events, and three with symptomatic radiation necrosis requiring surgery. Stereotactic interstitial radiosurgery performed using the PRS can obtain local control of cerebral metastases at rates that are comparable to those achieved through open resection and external stereotactic radiosurgery. The major advantage of using the PRS is that effective treatment can be accomplished at the time of stereotactic biopsy.

1404 POSTER Performance reproducibility of intra-operative radiotherapy equipment — photon radiosurgery system

1404 POSTER Performance reproducibility of intra-operative radiotherapy equipment — photon radiosurgery system

Interstitial Radiosurgery with the Photon Radiosurgery System in the Minimally-Invasive Treatment of Selected Deep-Seated Brain Tumors

SummaryThe purpose of this study was to evaluate the results of interstitial radiosurgery (IR) with Photon Radiosurgery System (PRS) in 18 patients (P) with deep-seated brain primary or secondary tumors. Follow-up varied from 2 to 53 months (mean, 13.6 mo). Seven P with glioblastomas died due to tumor progression. Five P with metastases died for systemic disease while local control was achieved in all. Six P with low-grade astrocytomas were well and imaging showed tumor control. We conclude that PRS IR is effective in the treatment of metastases while it provides lower benefit in malignant gliomas. It could play a major role in low-grade astrocytomas.

A Phase I study of intraoperative radiation therapy in children with recurrent brain tumors- a preliminary report

To describe the feasibility, toxicity and early efficacy of intraoperative radiation therapy (IORT) using the photon radiosurgery system (PRS)in children with recurrent brain tumors. The PRS incorporates a miniature 50 kV x-ray source capable of delivering a prescribed radiation dose directly into the surgical cavity using spherical applicators. Thus this treatment approach combines the advantages of surgery and RT with focused high RBE x-rays delivered directly into the tumor bed at a high dose rate. Between 2001 and 2004, 16 children were treated with IORT using the PRS at our institution on an IRB approved phase-I dose escalation protocol. Patients were classified into two groups. One group (Gp A) comprised of 8 children with recurrent tumors after surgery or chemotherapy (CT) and full dose RT (>50 Gy). In this group, 7 children had a posterior fossa ependymoma and 1 had a glioma. Most of them had multiple surgeries, one each had failed additional therapy with gamma knife radiosurgery (12 Gy) and high dose CT- bone marrow transplantation prior to IORT. The other group (Gp B) comprised of 8 children with recurrent tumors after surgery and / or chemotherapy but not RT. Among them 5 had supratentorial ependymoma, 1 each had glioma, astroblastoma and fibrosarcoma. All patients had pathologically confirmed tumor recurrence at surgery prior to IORT. The IORT dose was delivered using PRS applicators that ranged in size from 1.5–5 cm. The IORT dose was 10 Gy prescribed to a depth of 2mm in ten children, 10 Gy to 5mm in four children and 12 Gy to 2mm in two children on this dose escalation study. All patients were periodically evaluated by clinical and radiologic (MRI) examinations per protocol. The primary study end point was the development of unacceptable acute CNS toxicity (RTOG grade 3 or higher). The median follow up for all patients was 12 months (4–24 m). The median follow up in Gp A patients was 8 months (4–24 m), and four patients have been followed for more than one year after therapy. The median follow up for Gp B patients was 14 months (10–19m), and six have been followed for more than one year. There were no IORT-related complications in the intra or peri-operative period. The IORT procedure prolonged the duration of surgery by approximately 30 – 90 minutes for each patient. The median treatment time was 13.7 minutes (5.7–44). The median dose rate was 77.3 cGy/min (22.5–170). Two of 16 patients (12.5%) developed radiation necrosis approximately 3–4 months after IORT. Both of these patients belonged to GpB and had not received prior RT. Both of these patients received a dose of 10 Gy to a depth of 5mm. At the beginning of the study, the protocol allowed for the IORT dose to be prescribed to a depth of 2–5 mm. Thus four patients in GpB received 10 Gy to a depth of 5mm. Two of these four patients (50%) developed radiation necrosis. One developed symptomatic necrosis requiring surgery 5 months after IORT. Pathology revealed radiation necrosis without tumor. The other patient was asymptomatic and had spontaneous resolution of necrosis 15 months after IORT. None of the GpA patients developed radiation necrosis or any other complication following IORT despite previous full dose RT. Thus far, 11 patients (69%) have achieved tumor control after IORT, 5/8 (63%)in GpA and 6/8 (75%)in Gp B. Five patients in Gp A (63%) and 7 in Gp B (88%) are alive, 4 children died of tumor progression. This report describes the feasibility, safety and early efficacy of IORT (10 Gy to 2mm) delivered using the PRS in children with recurrent brain tumors, who may or may not have previously received full dose external RT. Majority of the previously irradiated children had tumors in the posterior fossa adjacent to the brain stem and fourth ventricle. IORT to a dose of 10 Gy prescribed to 5mm was associated with a high incidence of radiation necrosis and should not be performed especially in previously irradiated children. Patients are currently being enrolled at the next dose level (12 Gy to 2mm) of our dose-escalation study

Modelling the biological effect of a low-energy x-ray source used for intraoperative radiotherapy (IORT)

Low-energy x-rays are increasingly being used for intraoperative radiotherapy within and outside controlled trials. The Photon Radiosurgery System (PRS) is a miniaturized x-ray machine producing an essentially isotropic field of 30–50 kV x-rays. This device delivers a highly localized dose distribution and has been used for interstitial tumour irradiation and tumour-bed irradiation in different sites, including brain, abdomen and breast. However, prediction of the biological effect of such treatments is not straightforward because the increased relative biological effectiveness (RBE) of low-energy photons is influenced by the strong variation of dose associated with the non-uniform field and by repair during irradiation which may take up to 0.5–1 hour.

A Phase I study of intraoperative radiation therapy in children with recurrent brain tumors- a preliminary report

To describe the feasibility, toxicity and early efficacy of intraoperative radiation therapy (IORT) using the photon radiosurgery system (PRS)in children with recurrent brain tumors. The PRS incorporates a miniature 50 kV x-ray source capable of delivering a prescribed radiation dose directly into the surgical cavity using spherical applicators. Thus this treatment approach combines the advantages of surgery and RT with focused high RBE x-rays delivered directly into the tumor bed at a high dose rate.

Radiobiological effects of photon radiosurgery on choroid plexus cells in vitro.

The standard surgical treatment of hydrocephalus by cerebrospinal fluid (CSF) shunt is accompanied by numerous complications. The search for alternative treatment methods includes resection, coagulation and irradiation of part of the plexus choroideus. The reduction of CSF secretion after choroid plexus (CP) irradiation has been investigated only on the experimental level. The new Photon Radiosurgery System (PRS) now also provides clinically the opportunity to induce selective radionecrosis on the CP with high efficiency and safety. In order to achieve a basic understanding of the reaction of CP cells after PRS irradiation, we investigated the cell death after different irradiation doses using TB dye-exclusion and MTT assay on sheep choroid plexus (SCP) cells. We observed a dose-dependent decrease in cell survival with increasing doses of irradiation (9, 18, 27 and 36 Gy). Lower irradiation doses (9, 18 Gy) induced an initial decrease of cell survival. Cells were able to recover from day 6 on and achieved a similar cell viability compared to non-irradiated cells on day 12. In contrast, higher doses (27 and 36 Gy) of irradiation induced a constant decrease of the cell survival over 12 days. These results clearly demonstrate that PRS irradiation is able to induce radionecrosis of CP cells which are responsible for the secretion of CSF. Interstitial photon radiosurgery can provide the opportunity to deliver the irradiation dose locally to CP with minimal exposure of surrounding tissue. Our basic data support further studies investigating this concept in animal models and clinically.

Research progress in the last quarter of the 20th century at the University of Tokyo and Tokyo Women's Medical University.

Professor Keiji Sano described the history of neurosurgery in Japan until 1975. After World War II, not only neurosurgery but all fields of medicine were devastated in Japan. Professor Sano contributed greatly to the reform and modernization of neurosurgery during that very difficult era in Japan. He performed much research by himself and also as a leader of research groups on stereotactic and functional neurosurgery, cerebrovascular diseases, head injuries, and brain tumors. He organized the Fifth International Congress of Neurological Surgery in Tokyo in 1973. I succeeded in the chairmanship of the Department of Neurosurgery of the University of Tokyo in 1981. We have performed research on the treatment of brain tumors and cerebrovascular diseases. To obtain the best results for brain tumor treatment, we have introduced several new radiotherapeutic methods, such as the gamma knife, heavy-particle irradiation, and the photon radiosurgery system. To improve surgical treatment, we have energetically engaged in medical engineering research on computer-assisted surgical systems (intraoperative monitoring and navigation systems). We have also performed much research on chemotherapy and immunotherapy. In the field of cerebrovascular diseases, the main research projects have been focused on the mechanism and treatment of vasospasm and brain edema after subarachnoid hemorrhage. I summarize the results of our research performed in the Department of Neurosurgery of the University of Tokyo until 1992 and at Tokyo Women's Medical University after 1992, in the last quarter of the 20th century.

Use of Low-Energy X-Rays in the Treatment of Superficial Nonmelanomatous Skin Cancers

The Photon Radiosurgery System (PRS), developed by the Photoelectron Corporation in Lexington, Massachusetts, produces low-energy x-rays from the tip of a needle-like probe at a high dose-rate. This portable device can be located directly over the target volume, delivering a uniform dose while sparing surrounding normal structures. To evaluate its radiotherapeutic profile, a prospective phase I Food and Drug Administration trial was performed utilizing this device in the management of nonmelanomatous skin cancers. Target doses ranged from 10 Gray in one fraction to 30 Gray in three weekly fractions. Thirty-eight lesions in 18 patients were treated. The overall completed response rate for all histologies at 12 months was 83%. No significant acute or late morbidity was encountered. Our results to date demonstrate that low-energy x-rays produced by the PRS were as effective in managing nonmelanomatous skin tumors as other radiation treatment modalities without the need for cumbersome shielding or radiation precautions.

Targeted intra-operative radiotherapy (Targit): An innovative method of treatment for early breast cancer

We believe that conservative treatment of early breast cancer may not require radiotherapy that encompasses the whole breast. We present here the clinico-pathological basis for this view, as well as a novel therapeutic approach that allows intra-operative radiotherapy to be safely and accurately delivered to the target tissues in a standard operating theatre. THE RATIONALE: Whole-organ analysis of mastectomy specimens reveals that 80% of occult cancer foci are situated remote from the index quadrant. In contrast, over 90% of local recurrences after breast conservative therapy occur near the original tumour, even when radiotherapy is not given. Therefore, the remote occult cancer foci may be clinically irrelevant and radiotherapy to the index quadrant alone might be sufficient. A NOVEL TECHNIQUE: The Photon Radiosurgery System (PRS) is an ingenious portable electron-beam driven device that can typically deliver intra-operative doses of 5-20 Gy, respectively, to 1 cm and 0.2 cm from the tumour bed over about 22 min. The pliable breast tissue--the target--wraps around the source, providing perfect conformal radiotherapy. Being soft X-rays, the dose attenuates rapidly (alpha approximately 1/r3), reducing distant damage. In our pilot study of 25 patients (age 30-80 years, T = 0.42-4.0 cm), we replaced the routine post-operative tumour bed boost with targeted intra-operative radiotherapy. There have been no major complications and no patient has developed local recurrence, although the median follow-up time is short, at 24 months. It is safe and feasible to deliver targeted intraoperative radiotherapy (Targit) for early breast cancer. We have begun a randomised trial--the first of its kind--comparing Targit with conventional six-week course of radiotherapy. If proven equivalent in terms of local recurrence and cosmesis, it could eliminate the need for the usual six-week course of post-operative radiotherapy.