Re-irradiation of recurrent anaplastic ependymoma using radiosurgery or fractionated stereotactic radiotherapy

Purpose

Recurrent ependymomas were retreated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). The efficacy, toxicities, and differences between SRS and FSRT were analyzed.

Methods

Eight patients with recurrent ependymomas fulfilling the criteria described below were evaluated. Inclusion criteria were: (1) the patient had previously undergone surgery and conventional radiotherapy as first-line treatment; (2) targets were located in or adjacent to the eloquent area or were deep-seated; and (3) the previously irradiated volume overlapped the target lesion.

Results

FSRT was delivered to 18 lesions, SRS to 20 lesions. A median follow-up period was 23 months. The local control rate was 76 % at 3 years. No significant differences in local control were observed due to tumor size or fractionation schedule. Lesions receiving >25 Gy/5 fr or 21 Gy/3 fr did not recur within 1 year, whereas no dose–response relationship was observed in those treated with SRS. No grade ≥2 toxicity was observed.

Conclusion

Our treatment protocol provided an acceptable LC rate and minimal toxicities. Because local recurrence of tumors may result in patient death, a minimum dose of 21 Gy/3 fr or 25 Gy/5 fr or higher may be most suitable for treatment of these cases.

     

Increased signal intensity within glioblastoma resection cavities on fluid-attenuated inversion recovery imaging to detect early progressive disease in patients receiving radiotherapy with concomitant temozolomide therapy

Purpose

Our study tested the diagnostic accuracy of increased signal intensity (SI) within FLAIR MR images of resection cavities in differentiating early progressive disease (ePD) from pseudoprogression (PsP) in patients with glioblastoma treated with radiotherapy with concomitant temozolomide therapy.

Methods

In this retrospective study approved by our Institutional Review Board, we evaluated the records of 122 consecutive patients with partially or totally resected glioblastoma. Region of interest (ROI) analysis assessed 33 MR examinations from 11 subjects with histologically confirmed ePD and 37 MR examinations from 14 subjects with PsP (5 histologically confirmed, 9 clinically diagnosed). After applying an N4 bias correction algorithm to remove B0 field distortion and to standardize image intensities and then normalizing the intensities based on an ROI of uninvolved white matter from the contralateral hemisphere, the mean intensities of the ROI from within the resection cavities were calculated. Measures of diagnostic performance were calculated from the receiver operating characteristic (ROC) curve using the threshold intensity that maximized differentiation. Subgroup analysis explored differences between the patients with biopsy-confirmed disease.

Results

At an optimal threshold intensity of 2.9, the area under the ROC curve (AUROC) for FLAIR to differentiate ePD from PsP was 0.79 (95% confidence interval 0.686–0.873) with a sensitivity of 0.818 and specificity of 0.694. The AUROC increased to 0.86 when only the patients with biopsy-confirmed PsP were considered.

Conclusions

Increased SI within the resection cavity of FLAIR images is not a highly specific sign of ePD in glioblastoma patients treated with the Stupp protocol.

     

Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases

Purpose

The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases >?3?cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases.

Materials and methods

In two consecutive periods, 41?patients with 46?brain metastases received SRT with 1 fraction of 15?Gy, while 51?patients with 65?brain metastases received FSRT with 3?fractions of 8?Gy. We included patients with brain metastases with a planning target volume of >?13?cm³ or metastases in the brainstem.

Results

The minimum follow-up of patients still alive was 22?months. Comparing 1?fraction of 15?Gy ?with 3?fractions of 8?Gy, the 1-year rates of freedom from any local progression (54% and 61%, p?=?0.93) and pseudo progression (85% and 75%, p?=?0.25) were not significantly different. Overall survival rates were also not different.

Conclusion

The 1-year local progression and pseudo progression rates after 1 fraction of 15?Gy or 3?fractions of 8?Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary.     

Prognostic factors in recurrent glioblastoma multiforme and anaplastic astrocytoma treated with selective intra-arterial chemotherapy

BACKGROUND AND PURPOSE: Factors predictive of primary brain tumor outcome have been studied extensively, although the prognostic value of radiologic data, such as MR imaging and angiographic characteristics, has not been studied in depth. The purpose of this study was to determine whether radiologic data were prognostic factors among patients with recurrent glioblastoma multiforme and anaplastic astrocytoma treated with selective intra-arterial chemotherapy. METHODS: Forty-six patients were enrolled in a Phase II study of intra-arterial chemotherapy with carboplatin and Cereport (Alkermes Inc.; Cambridge, MA), a bradykinin analog that selectively increases permeability of the blood-tumor barrier. MR imaging volumes of enhancing tumor, resection cavity, and T2 signal abnormality were measured with T1-weighted and T2-weighted sequences. Volumes were analyzed individually and in various combinations. Tumor vascularity was graded on angiograms. Outcome was measured by time to tumor progression and survival. RESULTS: Of 46 patients included in this study, 41 underwent evaluation. Thirty were male and 11 were female; mean age was 48.5 years. Karnofsky scores ranged from 70 to 100. Thirty-two patients had glioblastoma multiforme, whereas nine had anaplastic astrocytoma. Twenty-eight patients had tumor progression and 13 had stable disease. Twenty-three patients died after an average of 205 days; 18 were surviving at an average of 324 days from the start of intra-arterial chemotherapy. In multivariate analysis, time from diagnosis to intra-arterial chemotherapy was predictive both of time to tumor progression and survival. Net tumor volume and vascularity also were significant for survival. Age, Karnofsky performance status, histologic findings, gender, MR imaging area, resection cavity volume, T2 signal abnormality volume, and various combined volumes were not significant. CONCLUSION: If confirmed by further studies, radiologic factors such as tumor volume and angiographic vascularity should be considered in design and stratification of future chemotherapy trials.     

Osteoradionecrosis after three-dimensional conformal radiotherapy for recurrent cervical cancer presenting as a progressive osteolytic lesion

Osteoradionecrosis (ORN) of the pelvic bone presenting as a progressive osteolytic lesion, following three-dimensional conformal radiotherapy (3DCRT) with concurrent chemotherapy, is a clinical diagnostic challenge that must be differentiated from an osseous metastasis. We report on a case with an unusual presentation of ORN mimicking bony metastasis that should be taken note of by physicians. A 46-year-old woman who had recurrent cervical cancer in the right pelvic sidewall underwent concurrent salvage chemoradiotherapy. She received 63 Gy 3DCRT. At 22 months, post-RT, an asymptomatic but enlarging osseous defect in the right ilium, located within the area covered by a 95% isodose line, was demonstrated on pelvic computed tomography (CT). ORN was confirmed by whole-body [18F] fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET) CT scan and CT-guided bone biopsy. A localized, growing ORN of pelvic bone after high-dose 3DCRT is an uncommon late complication. Differential diagnosis between ORN and bony metastasis may be possible with low FDG uptake of ORN on PET-CT scans.     

Reirradiation for recurrent head and neck cancers using charged particle or photon radiotherapy

Objective

To examine the outcomes of reirradiation for recurrent head and neck cancers using different modalities.

Methods

This retrospective study included 26 patients who received charged particle radiotherapy (CP) and 150 who received photon radiotherapy (117 CyberKnife radiotherapy [CK] and 36 intensity-modulated radiotherapy [IMRT]). Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias.

Results

Higher prescribed doses were used in CP than photon radiotherapy. The 1?year overall survival (OS) rates were 67.9% for CP and 54.1% for photon radiotherapy (p = 0.15; 55% for CK and 51% for IMRT). In multivariate Cox regression, the significant prognostic factors for better survival were nasopharyngeal cancer, higher prescribed dose, and lower tumor volume. IPTW showed a statistically significant difference between CP and photon radiotherapy (p = 0.04). The local control rates for patients treated with CP and photon radiotherapy at 1 year were 66.9% (range 46.3–87.5%) and 67.1% (range 58.3–75.9%), respectively. A total of 48 patients (27%) experienced toxicity grade ≥3 (24% in the photon radiotherapy group and 46% in the CP group), including 17 patients with grade 5 toxicity. Multivariate analysis revealed that younger age and a larger planning target volume (PTV) were significant risk factors for grade 3 or worse toxicity.

Conclusion

CP provided superior survival outcome compared to photon radiotherapy. Tumor volume, primary site (nasopharyngeal), and prescribed dose were identified as survival factors. Younger patients with a larger PTV experienced toxicity grade ≥3.

     

Pulsed-dose rate brachytherapy with concomitant chemotherapy and interstitial hyperthermia in patients with recurrent head-and-neck cancer

PURPOSE: We attempted in our clinic to evaluate the efficacy and feasibility of a simultaneous application of a cis-platinum-based chemotherapy and interstitial hyperthermia to interstitial pulsed-dose rate (PDR) brachytherapy in patients with recurrent head-and-neck cancer. METHODS AND MATERIALS: Between April 1999 and September 2001, 15 patients with recurrent head-and-neck cancer were treated with PDR brachytherapy, chemotherapy, and interstitial hyperthermia. All patients had received prior radiation therapy. A dose per pulse of 0.46 to 0.55 Gy was given up to a median total dose of 55 Gy. Simultaneously to the PDR brachytherapy, chemotherapy was given with cis-platinum 20 mg/m2 as a short i.v. infusion each day and 5-fluorouracil 800 mg/m2 by continuous infusion from Day 1 to Day 5. After the PDR brachytherapy was finished, all patients were treated with a single session of interstitial hyperthermia. RESULTS: All the patients could receive the whole treatment. After treatment, only mild oral mucositis occurred. One patient developed soft tissue ulceration. None of the patients developed osteoradionecrosis. After a median follow-up of 6 months, the local tumor control rate was 80% (12 of 15), and the 2-year overall survival was 67% (10 of 15). CONCLUSIONS: The intensification of the interstitial PDR brachytherapy with chemotherapy and hyperthermia is feasible and safe, and the preliminary results are encouraging.     

Reirradiation for recurrent malignant brain tumor with radiotherapy or proton beam therapy

Background and purpose

Radiotherapy for recurrent malignant brain tumors is usually limited because of the dose tolerance of the normal brain tissue. The goal of the study was to evaluate the efficacy and feasibility of reirradiation for patients with recurrent malignant brain tumors.

Patients and methods

The subjects comprised 26 patients with recurrent malignant brain tumors treated with conventional radiotherapy (RT, n?=?8), stereotactic radiotherapy (SRT, n?=?10), and proton beam therapy (PBT, n?=?8) at our institute. Fifteen patients had glioblastoma, 6 had WHO grade 3 glioma, and 5 had other tumors. The dose of initial radiotherapy was 34.5–94.4 Gy. Different radiation schedules were compared using the equivalent dose in 2-Gy fractions.

Results

Reirradiation was completed in all patients without a severe acute reaction. The reirradiation doses were 30–60 Gy (median, 42.3 Gy) and the total doses for the initial and second treatments were 64.5–150.4 Gy (median, 100.0 Gy). Currently, 11 patients are alive (median follow-up period, 19.4 months) and 15 are dead. The median survival and local control periods after reirradiation of the 26 patients were 18.3 and 9.3 months, respectively. For the 15 patients with glioblastoma, these periods were 13.1 and 11.0 months, respectively. Two patients showed radiation necrosis that was treated by surgery or conservative therapy.

Conclusion

Reirradiation for recurrent malignant brain tumor using conventional RT, SRT, or PBT was feasible and effective in selected cases. Further investigation is needed for treatment optimization for a given patient and tumor condition.     

Postoperative local fractionated radiotherapy for resected single brain metastases

Purpose

Evaluation of postoperative fractionated local 3D-conformal radiotherapy (3DRT) of the resection cavity in brain metastases.

Patients and methods

Between 2011 and 2016, 57 patients underwent resection of a single, previously untreated (37/57, 65%) or recurrent (20/57, 35%) brain metastasis (median maximal diameter 3.5?cm [1.1–6.5?cm]) followed by 3DRT. For definition of the gross tumor volume (GTV), the resection cavity was used and for the clinical target volume (CTV), margins of 1.0–1.5 cm were added. Median dose was 48.0?Gy (30.0–50.4?Gy) in 25 (10–28) fractions; most patients had 36.0–42.0?Gy in 3.0?Gy fractions (n?=?16, EQD2_10Gy 39.0–45.5?Gy) or 40.0–50.4?Gy in 1.8–2.0?Gy fractions (n?=?37, EQD2_10Gy 39.3–50.0?Gy).

Results

Median follow-up was 18 months. Local control rates were 83% at 1 year and 78% at 2 years and were significantly influenced by histology (breast cancer 100%, non-small lung cancer 87%, melanoma 80%, colorectal cancer 26% at 2 years, p?=?0.006) and resection status (p?<?0.0001), but not by EQD2_10Gy or size of the planning target volume (median 96.7?ml [16.7–282.8?ml]). At 1 and 2 years, 74% and 52% of the patients were free from distant brain metastases. Salvage procedures were applied in 25/27 (93%) of recurrent patients. Survival was 68% at 1 year and 41% at 2 years and was significantly improved in younger patients (p?=?0.006) with higher Karnofsky performance score (p?<?0.0001) and without prior radiotherapy (54% vs. 9% at 2 years, p?=?0.006). No cases of radiographic or symptomatic radionecrosis were observed.

Conclusion

Adjuvant fractionated local 3DRT is highly effective in radiosensitive, completely resected metastases and should be considered for treating large resection cavities as an alternative to postoperative stereotactic single dose or hypofractionated radiosurgery.

     

Clinical commissioning of Laitinen Stereoadapter for fractionated stereotactic radiotherapy

The Laitinen Stereoadapter 5000 from Sandstroem Trade and Technology was acceptance tested and commissioned for clinical use in a Fractionated Stereotactic Radiotherapy Program at our facility. The frame was implemented to function as a localization device for target delineation rather than as an immobilization device. The frame is of non-invasive nature utilizing ear plugs and a nasion bridge adapter as the connecting points with the patient’s head. The reproducibility of the head frame position with respect to external skull reference points was tested. CT and MRI imaging studies were performed on a patient phantom with the stereoadapter in place. The target was delineated and target coordinates were calculated for two implanted targets. The phantom was positioned according to the target coordinates on a Siemens MXE Linear Accelerator by aid of the target positioning lasers. Radiographic port film images were taken with the circular fields typically used in stereotactic radiosurgery. A complete treatment isodose plan was performed and dosimetric accuracy was tested by positioning a small volume ionization chamber at the center of the target volume in the head phantom. The results of these tests were found to be clinically acceptable.     

Clinical commissioning of Laitinen Stereoadapter for fractionated stereotactic radiotherapy

The Laitinen Stereoadapter 5000 from Sandstroem Trade and Technology was acceptance tested and commissioned for clinical use in a Fractionated Stereotactic Radiotherapy Program at our facility. The frame was implemented to function as a localization device for target delineation rather than as an immobilization device. The frame is of non-invasive nature utilizing ear plugs and a nasion bridge adapter as the connecting points with the patient’s head. The reproducibility of the head frame position with respect to external skull reference points was tested. CT and MRI imaging studies were performed on a patient phantom with the stereoadapter in place. The target was delineated and target coordinates were calculated for two implanted targets. The phantom was positioned according to the target coordinates on a Siemens MXE Linear Accelerator by aid of the target positioning lasers. Radiographic port film images were taken with the circular fields typically used in stereotactic radiosurgery. A complete treatment isodose plan was performed and dosimetric accuracy was tested by positioning a small volume ionization chamber at the center of the target volume in the head phantom. The results of these tests were found to be clinically acceptable.     

Low-dose external beam radiotherapy for greater trochanteric pain syndrome

Purpose

Low-dose external beam radiotherapy (ED-EBRT) is frequently used in the therapy of refractory greater trochanteric pain syndrome (GTPS). As studies reporting treatment results are scarce, we retrospectively analyzed our own patient collectives.

Patients and methods

In all, 60 patients (74 hips) received LD-EBRT (6 × 0.5 Gy in 29 hips, 6 × 1 Gy in 45). The endpoint was the patient’s reported subjective response to treatment. The influence of different patient and treatment characteristics on treatment outcome was investigated.

Results

At the end of LD-EBRT, 69% reported partial remission, 4% complete remission, no change 28%. A total of 3 months later (n = 52 hips), the results were 37, 33, and 30% and 18 months after LD-EBRT (n = 47) 21, 51, and 28%. In univariate analysis “inclusion of the total femoral head into the PTV” and “night pain before LD-EBRT” were correlated with symptom remission at the end of LD-EBRT, while “initial increase in pain during LD-EBRT” was significantly associated with treatment failure. In multivariable modeling “initial increase in pain” was identified as a risk factor for treatment failure (p = 0.007; odds ratio [OR] 0.209; 95% confidence interval [CI] 0.048–0.957), while “night pain” was an independent factor for remission (p = 0.038; OR 3.484; 95% CI 1.004–12.6). Three months after LD-EBRT “night pain” and “inclusion of the complete femoral neck circumference into the PTV” were predictive for remission.

Conclusion

LD-EBRT represents a useful treatment option for patients suffering from GTPS. Three months after therapy two-thirds of the patients reported a partial or complete symptom remission. Especially patients who suffered from nocturnal pain seemed to benefit. Treatment appeared to be more effective when the entire circumference of the femoral neck was encompassed.

     

大分割和常规分割放疗联合化疗治疗食管癌术后气管食管沟淋巴结转移的随机对照研究

目的 探讨大分割放疗（HFR）联合紫杉醇周剂量化疗治疗食管癌术后气管食管沟淋巴结（TGLN）的安全性和疗效。方法 将53例食管癌术后单纯TGLN转移的患者随机抛硬币法分为两组,大分割组25例采用60 Gy/20次放疗,常规分割组28例采用60 Gy/30次放疗,两组患者放疗同时均采用紫杉醇 50 mg周剂量化疗。比较两种不同分割方式对不良反应及预后的影响。结果大分割组和常规分割组患者3~4级放射性食管炎、肺炎发生率分别为44.0%、16.0%和25.0%、7.1%,两组比较差异无统计学意义（P>0.05）。两组近期有效率比较,差异无统计学意义（P>0.05）。淋巴结转移灶直径≤2 cm患者近期有效率高于淋巴结转移灶直径>2 cm的患者（P<0.05）。大分割组和常规分割组中位总生存期（OS）分别为24.2个月（95%CI 16.2~32.1）和11.8个月（95%CI 9.2~14.4）,两组比较差异有统计学意义（χ²=5.063,P<0.05）。单因素和多因素分析均显示淋巴结直径和分割方式是影响患者预后的因素（P<0.05）。结论 大分割放疗联合紫杉醇周剂量化疗治疗食管癌术后气管食管沟淋巴结较常规分割提高了患者预后,且治疗并发症未明显增加。