Dynamic CT angiography for cyberknife radiosurgery planning of intracranial arteriovenous malformations: a technical/feasibility report

Background.

Successful radiosurgery for arteriovenous malformations (AVMs) requires accurate nidus delineation in the 3D treatment planning system (TPS). The catheter biplane digital subtraction angiogram (DSA) has traditionally been the gold standard for evaluation of the AVM nidus, but its 2D nature limits its value for contouring and it cannot be imported into the Cyberknife TPS. We describe a technique for acquisition and integration of 3D dynamic CT angiograms (dCTA) into the Cyberknife TPS for intracranial AVMs and review the feasibility of using this technique in the first patient cohort.

Patients and methods.

Dynamic continuous whole brain CT images were acquired in a Toshiba 320 volume CT scanner with data reconstruction every 0.5 sec. This multi-time-point acquisition enabled us to choose the CT data-set with the clearest nidus without significant enhancement of surrounding blood vessels. This was imported to the Cyberknife TPS and co-registered with planning CT and T2 MRI (2D DSA adjacent for reference). The feasibility of using dCTA was evaluated in the first thirteen patients with outcome evaluation from patient records.

Results.

dCTA data was accurately co-registered in the Cyberknife TPS and appeared to assist in nidus contouring for all patients. Imaging modalities were complementary. 85% of patients had complete (6/13) or continuing partial nidus obliteration (5/13) at 37 months median follow-up.

Conclusions.

dCTA is a promising imaging technique that can be successfully imported into the Cyberknife TPS and appears to assist in radiosurgery nidus definition. Further study to validate its role is warranted.     

The efficacy of fractionated radiotherapy and stereotactic radiosurgery for pituitary adenomas: long-term results of 125 consecutive patients treated in a single institution

BACKGROUND: The objective of this retrospective cohort study was to define the efficacy and safety of fractionated radiotherapy (FRT) and stereotactic radiosurgery (SRS) for the treatment of patients with pituitary adenoma. METHODS: Between January 1995 and April 2006, 125 consecutive patients with pituitary adenomas (54 hormone-secreting adenomas and 71 nonsecretory adenomas) received FRT or underwent SRS. Sixty-four patients received FRT, for which the mean total dose was 50.4 grays (Gy) (range, 48-54 Gy), and 61 patients underwent gamma-knife SRS with mean marginal dose of 25.1 Gy (range, 9-30 Gy). RESULTS: After mean follow up of 36.7 months, the tumor volume was increased in only 4 patients (3.2%). The overall actuarial progression-free survival rate was 99% at 2 years and 97% at 4 years. No difference was observed between the FRT group and the SRS group in the control of tumor growth. Based on the endocrinologic results in the patients who had secretory adenomas, the overall hormone complete remission rate was 26.2% at 2 years and 76.3% at 4 years. The median time to complete remission was 26 months in the SRS group and 63 months in the FRT group (P = .0068). Hypopituitarism developed as a delayed complication in 11.5% of patients at a median of 84 months. CONCLUSIONS: Both FRT and SRS were efficient treatment modalities for the control of tumor growth in patients with pituitary adenomas. The current results indicated that single-dose radiosurgery more promptly produces an effect on the hypersecretion of pituitary hormones and may be recommended over FRT for suitable patients.     

Immunohistochemistry as a predictor of clinical outcome in patients given postoperative radiation for subtotally resected pituitary adenomas

Summary There is general agreement that postoperative radiation therapy is beneficial for patients with subtotally resected pituitary adenomas. We have identified 41 such patients treated during a 20-year period who received postoperative irradiation for a pituitary adenoma. The usual dose was 5040 cGy in 28 fractions. The mean follow-up time was 10.3 years. On routine hematoxylin and eosin (H&E) staining, there were thirty-three chromophobe, seven eosinophilic, and one basophilic adenoma. Tissue blocks were stained for growth hormone (GH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin (PRL), and/or adrenocorticotropin ACTH) using the peroxidase-antiperoxidase immunohistochemistry (IHC) method. Routine H&E staining was a poor predictor of the IHC stain. While most patients with a known clinical endocrine syndrome stained positive on IHC for the suspected offending hormone, many patients without a clinical syndrome also stained positive indicating the presence of hormonally occult adenomas in this locally invasive group. The IHC stain results were compared to clinical outcome. The presence of positive GH IHC staining decreased the 15-year progression-free survival (PFS) from 100% to 64% compared to GH negative adenomas (p=0.06). There was a trend toward decreased 15-year PFS in patients who did not stain for LH. Positive staining for prolactin, ACTH, or TSH had no influence on the progression-free survival. We conclude that additional prognostic information can be obtained in this subset of patients (by performing IHC analysis) that is not known by the clinical presentation or appearance on H&E stain.Supported by the American Cancer Society Clinical Oncology Career Development Award.     

Efficacy and morbidity of arc-therapy radiosurgery for cerebral arteriovenous malformations: a comparison with the natural history

PURPOSE: To report the results of arc-therapy radiosurgery for cerebral arteriovenous malformation (AVM) and to compare the adverse event rate with the rate expected from the natural history. METHODS AND MATERIALS: We performed a retrospective study of our 118 first patients with a mean follow-up of 46 months (range, 5-105 months). The AVMs had features indicating a poor prognosis at initial presentation and had already been treated by previous embolizations in 88% of patients. The mean volume of the targets was 7.4 cm3 (range, 0.3-28.3 cm3). The mean minimal and maximal dose was 17.7 Gy (range, 10-25 Gy) and 24.5 Gy (range, 17-36 Gy), respectively. RESULTS: The crude and 5-year actuarial rate of cure (total obstruction of the AVM shunt at angiography) was 54% (60 of 112) and 77%, respectively. The only independent prognostic factor of cure was the AVM volume (crude cure rate 67% for <7 cm3 vs. 35% for > or =7 cm3; p = 0.001). No patient died. Transient and permanent complications and hemorrhage occurred in 5%, 1.7%, and 6% of patients, respectively. The annual risk of an adverse event (hemorrhage or complication) was 3.9%. CONCLUSION: The results of our series showed that radiosurgery, performed alone or after prior shrinkage of the AVM by embolization, is both effective and well tolerated, with a rate of adverse events comparable to that expected from the natural history.     

三维适形放疗与立体定向放射外科治疗脑胶质瘤初步临床分析

目的分析三维适形放疗(3DCRT)与立体定向放射外科(SRS)对于不能手术切除或拒绝手术治疗的脑胶质瘤的疗效。方法对46例不能手术或拒绝接受手术治疗的脑胶质瘤患者随机分为两组,3DCRT组24例,SRS组22例。3DCRT组施行三维适形放疗,SRS组施行立体定向放射外科治疗。结果3DCRT组患者1、2、3年生存率分别是91.7%、54.2%和8.3%,SRS组分别是80.9%、47.6%、4.8%,两组间比较无显著性差异(P=0.6487)。3DCRT组放射性脑水肿发生率为66.7%,SRS组为95.5%,两组间差异有显著性(P<0.05)。结论3DCRT与SRS放射治疗脑胶质瘤生存率相似。SRS放射性脑水肿反应明显高于3DCRT,3DCRT较SRS易为患者耐受。采用非手术疗法治疗脑胶质瘤,3DCRT可能是一种适宜的放射治疗方法。     

Gamma Knife radiosurgery for cerebral arteriovenous malformations in children/adolescents and adults. Part II: Differences in obliteration rates, treatment-obliteration intervals, and prognostic factors

PURPOSE: To evaluate and compare obliteration rates (OBRs) and treatment-obliteration intervals (TOIs) for cerebral arteriovenous malformations (cAVMs) treated with Gamma Knife radiosurgery in children/adolescents and adults; and to determine factors predicting the OBR and TOI in these two populations. METHODS AND MATERIALS: This study concerned 62 children/adolescents and 193 adults observed for > or = 3 years. Fisher exact two-tailed and Wilcoxon rank-sum tests, multiple logistics, and Cox proportional hazard models were used for statistical analysis. RESULTS: The overall OBR was 85.5% in children/adolescents and 87.6% in adults (p = 0.671), but children/adolescents showed higher 36-month actuarial OBRs (69.35%) and shorter median TOIs (25.7 months) than adults (66.84% and 28.2 months; p = 0.006 and p = 0.017, respectively). In children/adolescents, lower Spetzler-Martin grades (p = 0.043) and younger age (p = 0.019) correlated significantly with OBRs, and lower Spetzler-Martin grades (p = 0.024) and noneloquent cAVM locations (p = 0.046) with TOIs. In adults, low flow through the cAVM and < 6.2-cm3 volume were associated with both OBR and TOI (p = 0.012 and p = 0.002, respectively). CONCLUSIONS: The differences in OBRs within 3 years and TOIs, although slight, seem to show that pediatric cAVMs behave differently from those in adults after Gamma Knife radiosurgery.     

Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases

PURPOSE: To evaluate the feasibility and efficacy of hypofractionated stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS AND MATERIALS: The records of 69 patients with 174 metastatic liver lesions treated with SBRT between April 2001 and October 2004 were reviewed. The most common primary tumors were colorectal (n = 20), breast (n = 16), pancreas (n = 9), and lung (n = 5). The mean number of lesions treated per patient was 2.5 (range, 1-6). The longest diameter of the lesions ranged in size from 0.6 to 12.2 cm (median, 2.7 cm). Dose per fraction ranged from 2 Gy to 6 Gy, with a median total dose of 48 Gy (range, 30-55 Gy). Dose was prescribed to the 100% isodose line (IDL), with the 80% IDL covering the gross tumor volume with a minimum margin of 7 mm. RESULTS: The median follow up was 14.5 months. Sixty patients were evaluable for response based on an abdominal computed tomography scan obtained at a minimum of 3 months after completion of SBRT. The actuarial overall infield local control rate of the irradiated lesions was 76% and 57% at 10 and 20 months, respectively. The median overall survival time was 14.5 months. The progression-free survival rate was 46% and 24% at 6 and 12 months, respectively. None of the patients developed Grade 3 or higher toxicity. CONCLUSION: Hypofractionated SBRT provides excellent local control with minimal side effects in selected patients with limited hepatic metastases.     

Dose as a function of liver volume and planning target volume in helical tomotherapy, intensity-modulated radiation therapy-based stereotactic body radiation therapy for hepatic metastasis

PURPOSE: Stereotactic body radiation therapy (SBRT) has been shown to be an effective, well-tolerated treatment for local control of tumors metastatic to the liver. Multi-institutional Phase II trials are examining 60 Gy in 3 fractions delivered by linac-based, 3D-conformal IMRT. HiArt Helical TomoTherapy is a treatment unit that delivers co-planar helical IMRT that is capable of image-guided SBRT. We hypothesized that the maximum tolerable dose (MTD) delivered to a lesion by Helical TomoTherapy-based SBRT could be predicted based on the planning target volume (PTV) and liver volume. METHODS AND MATERIALS: To test this, we performed inverse treatment planning and analyzed the dosimetry for multiple hypothetical liver gross tumor volumes (GTV) with conventional PTV expansions. Inverse planning was carried out to find the maximum tolerated SBRT dose up to 60 Gy to be delivered in 3 fractions based on the dose constraint that 700 cc of normal liver would receive less than 15 Gy. RESULTS: Regression analysis indicated a linear relationship between the MTD, the PTV and the liver volume, supporting our hypothesis. A predictive equation was generated, which was found to have an accuracy of +/-3 Gy. In addition, dose constraints based on proximity to other normal tissues were tested. Inverse planning for PTVs located at varying distances from the heart, small bowel, and spinal cord revealed a predictable decrease in the MTD as the PTV increased in size or approached normal organs. CONCLUSIONS: These data provide a framework for predicting the likely MTD for patients considered for Helical TomoTherapy liver SBRT.     

Skin CanceR Brachytherapy vs External beam radiation therapy (SCRiBE) meta-analysis

Background and purpose

To compare cosmesis and local recurrence (LR) of definitive external beam radiation therapy (EBRT) vs brachytherapy (BT) for indolent basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin.

A concurrent ultra‐fractionated radiation therapy and temozolomide treatment: A promising therapy for newly diagnosed,inoperable glioblastoma

We report on a phase II clinical trial to determine the effect of a concurrent ultra‐fractionated radiotherapy and temozolomide treatment in inoperable glioblastoma patients. A phase II study opened; patients over 18 years of age who were able to give informed consent and had histologically proven, newly diagnosed inoperable diagnosed and supratentorial glioblastoma were eligible. Three doses of 0.75 Gy spaced apart by at least 4 hr were delivered daily, 5 days a week for six consecutive weeks for a total of 67.5 Gy. Chemotherapy was administered during the same period, which consisted of temozolomide given at a dose of 75 mg/m² for 7 days a week. After a 4‐week break, chemotherapy was resumed for up to six cycles of adjuvant temozolomide treatment, given every 28 days, according to the standard 5‐day regimen. Tolerance and toxicity were the primary endpoints; survival and progression‐free survival were the secondary endpoints. In total, 40 patients were enrolled in this study, 29 men and 11 women. The median age was 58 years, and the median Karnofsky performance status was 80. The concomitant ultra‐fractionated radiotherapy and temozolomide treatment was well tolerated. Complete responses were seen in four patients, and partial responses were reported in seven patients. The median survival from the initial diagnosis was 16 months. Several long‐term survivors were noted. Concurrent ultra‐fractionated radiation therapy and temozolomide treatment are well accepted by the patients. The results showed encouraging survival rates for these unfavorable patients.     

Conventional, conformal, and intensity-modulated radiation therapy treatment planning of external beam radiotherapy for cervical cancer: The impact of tumor regression

PURPOSE: Investigating the impact of tumor regression on the dose within cervical tumors and surrounding organs, comparing conventional, conformal, and intensity-modulated radiotherapy (IMRT) and the need for repeated treatment planning during irradiation. METHODS AND MATERIALS: Fourteen patients with cervical cancer underwent magnetic resonance (MR) imaging before treatment and once during treatment, after about 30 Gy. Target volumes and critical organs were delineated. First conventional, conformal, and IMRT plans were generated. To evaluate the impact of tumor regression, we calculated dose-volume histograms for these plans, using the delineations of the intratreatment MR images. Second conformal and IMRT plans were made based on the delineations of the intratreatment MR images. First and second plans were compared. RESULTS: The average volume receiving 95% of the prescribed dose (43 Gy) by the conventional, conformal, and IMRT plans was, respectively, for the bowel 626 cc, 427 cc, and 232 cc; for the rectum 101 cc, 90 cc, and 60 cc; and for the bladder 89 cc, 70 cc, and 58 cc. The volumes of critical organs at this dose level were significantly reduced using IMRT compared with conventional and conformal planning (p < 0.02 in all cases). After having delivered about 30 Gy external beam radiation therapy, the primary gross tumor volumes decreased on average by 46% (range, 6.1-100%). The target volumes on the intratreatment MR images remained sufficiently covered by the 95% isodose. Second IMRT plans significantly diminished the treated bowel volume, if the primary gross tumor volumes decreased >30 cc. CONCLUSIONS: Intensity-modulated radiation therapy is superior in sparing of critical organs compared with conventional and conformal treatment, with adequate coverage of the target volumes. Intensity-modulated radiation therapy remains superior after 30 Gy external beam radiation therapy, despite tumor regression and internal organ motion. Repeated IMRT planning can improve the sparing of the bowel and rectum in patients with substantial tumor regression.     

Small cell carcinoma of the lung: Results of combination chemotherapy and radiation therapy (COF vs. COFP randomized analyzed)

Forty-three patients with small cell carcinoma were admitted to our hospital in 1977. These patients were treated with combined chemotherapy and radiotherapy, the latter being CO⁶⁰ or 8 MEV Linac. The protocol for treatment is the following: 1) Chemotherapy, randomized into two groups COF (Cytoxan, Vincristin, and 5-fluorouracil) and COFP (Cytoxan, Vincristin, 5-Fu and Procabazine). 2) Radiotherapy with 2 split courses. In the rest period chemotherapy was given as randomized above for COF and COFP groups, but drugs given only once in this rest period, followed by the whole course of radiotherapy using same drugs as above, but only once a month for at least 2 years. The 1-year survival rates were 63.1% and 57.8% respectively, 2-year survival rates were 21% for both programs, and 3-year survival rates were 10.5% for both programs also. Therefore, we believe that procarbazine does not play a very important role in the program, and can be dispensed with. Compared with international reports, the efficacy of COF and COFP programs is as good as any other of the combined chemotherapy programs in the world. These programs may be of more benefit to the patients because of the very mild toxicity and very low cost. In this study the extent of the lesion was found to play important role in prognosis, in other words, the earlier the stage the better the results, just as for other solid tumors. Median survival time in Stage II groups is 20 months, the 1-y7ear survival rate is 81.8% ($\text{8}\text{11}$, 2-year survival 45.4% ($\text{5}\text{11}$), while in Stage II groups is median survival time is 11.5 months, the 1-year survival rate is 57.1% ($\text{13}\text{21}$), and 2-year survival rate is 14.2% ($\text{2}\text{21}$). Because the survival time exceeded 18 months, there are 10 of 15 patients alive and without evidence of disease (66.6%), and 6 of 8 patients alive over 24 months without evidence of disease (75%). We offer a program that for maintenance combined chemotherapy periods should be prolonged to 2–3 or more years.     

Image-guided,intensity-modulated radiation therapy (IG-IMRT) for skull base chordoma and chondrosarcoma: preliminary outcomes

Background

We report our preliminary outcomes following high-dose image-guided intensity modulated radiotherapy (IG-IMRT) for skull base chordoma and chondrosarcoma.

Methods

Forty-two consecutive IG-IMRT patients, with either skull base chordoma (n = 24) or chondrosarcoma (n = 18) treated between August 2001 and December 2012 were reviewed. The median follow-up was 36 months (range, 3–90 mo) in the chordoma cohort, and 67 months (range, 15–125) in the chondrosarcoma cohort. Initial surgery included biopsy (7% of patients), subtotal resection (57% of patients), and gross total resection (36% of patients). The median IG-IMRT total doses in the chondrosarcoma and chordoma cohorts were 70 Gy and 76 Gy, respectively, delivered with 2 Gy/fraction.

Results

For the chordoma and chondrosarcoma cohorts, the 5-year overall survival and local control rates were 85.6% and 65.3%, and 87.8% and 88.1%, respectively. In total, 10 patients progressed locally: 8 were chordoma patients and 2 chondrosarcoma patients. Both chondrosarcoma failures were in higher-grade tumors (grades 2 and 3). None of the 8 patients with grade 1 chondrosarcoma failed, with a median follow-up of 77 months (range, 34–125). There were 8 radiation-induced late effects—the most significant was a radiation-induced secondary malignancy occurring 6.7 years following IG-IMRT. Gross total resection and age were predictors of local control in the chordoma and chondrosarcoma patients, respectively.

Conclusions

We report favorable survival, local control and adverse event rates following high dose IG-IMRT. Further follow-up is needed to confirm long-term efficacy.     

Margin width as a determinant of local control with and without radiation therapy for ductal carcinoma in situ (DCIS) of the breast

In order to assess the utility of margin width in relation to other histopathologic features as a determinant of local control in ductal carcinoma in situ (DCIS) of the breast, we retrospectively examined the treatment of 109 breasts treated with (n = 54) or without adjuvant radiotherapy (n = 55). Median follow‐up was 49 and 54 months for patients treated with excision alone (E) or excision plus adjuvant radiotherapy (E+XRT), respectively. Cases treated with E+XRT were significantly larger and had a trend towards closer surgical margins than those treated with E alone. For all cases, margin width ≤1 mm and lesion diameter >15 mm were significantly associated with increased local recurrence. Lesion size ≤15 mm was associated with no cases of local failure regardless of treatment arm. For lesions >15 mm in diameter, there was a significant decrease in 5‐year local failure with E+XRT compared to E alone (21% vs. 36%, P = 0.03). Tumor margin >1 mm was associated with a low rate of 5‐year local failure for either E alone or E+XRT (10.9% vs. 4.6%, P = NS). Tumor margin ≤1 mm had a high rate of local failure that was not significantly decreased by the addition of adjuvant radiotherapy. These results show that large diameter (>15mm) and close surgical margins (≤1 mm) are the dominant risk factors for local recurrence in DCIS. E+XRT significantly decreased local failure risk compared to E alone for large lesions but not for those with close margins. © 2002 Wiley‐Liss, Inc.