Clinical outcome of stereotactic body radiotherapy of 54 Gy in nine fractions for patients with localized lung tumor using a custom-made immobilization system

Purpose

The aim of this study was to investigate the clinical outcome of stereotactic body radiotherapy (SBRT) of 54?Gy in nine fractions for patients with localized lung tumor using a custom-made immobilization system.

Methods and materials

The subjects were 19 patients who had localized lung tumor (11 primaries, 8 metastases) between May 2003 and October 2005. Treatment was conducted on 19 lung tumors by fixed multiple noncoplanar conformal beams with a standard linear accelerator. The isocentric dose was 54?Gy in nine fractions. The median overall treatment time was 15 days (range 11–22 days). All patients were immobilized by a thermo-shell and a custom-made headrest during the treatment.

Results

The crude local tumor control rate was 95% during the follow-up of 9.4–39.5 (median 17.7) months. In-field recurrence was noted in only one patient at the last follow-up. The Kaplan-Meier overall survival rate at 2 years was 89.5%. Grade 1 radiation pneumonia and grade 1 radiation fibrosis were observed in 12 of the 19 patients. Treatment-related severe early and late complications were not observed in this series.

Conclusion

The stereotactic body radiotherapy of 54?Gy in nine fractions achieved acceptable tumor control without any severe complications. The results suggest that SBRT can be one of the alternatives for patients with localized lung tumors.

     

Experimental stereotactic irradiation of normal rabbit lung: computed tomographic analysis of radiation injury and the histopathological features

Purpose The aim of this study was to establish an animal experimental model of pulmonary stereotactic irradiation and clarify the morphological patterns of pulmonary radiation injury with computed tomography and the histopathological features. Materials and methods Tiny spherical regions in the lungs of seven anesthetized rabbits were irradiated stereotactically with a single fractional dose of 21–60 Gy. Subsequently, the irradiated lungs were observed biweekly with computed tomography (CT) for 24 weeks. Radiation injury of the lung was examined histopathologically in one specimen. Results Localized hypodense changes were observed 7–15 weeks after irradiation in three rabbits irradiated with 60 Gy, and the findings persisted beyond that time. The electron density ratios in the lung fields obtained from the CT images were shown to be decreasing, corresponding to the hypodensity changes. No clear increased density opacity was observed in any rabbit in the 60-Gy irradiated group. Severe localized fibrotic change was observed in the histopathological specimens. Conclusion Specific localized hypodensity changes were found in only three rabbits irradiated with 60 Gy, the highest dose we employed.     

Unusual behavior of foreign body granuloma that grew rapidly in the radiation field during radiation therapy

We report our experience with two cases of a rapidly growing benign tumor in the radiation field despite radiotherapy. Case 1 was a 75-year-old man who was diagnosed as having postoperative recurrence of esophageal carcinoma in the right chest wall and underwent radiotherapy. A small nodule in the recurrent lesion grew to 20 mm in diameter at 70 Gy. The biopsy specimen was diagnosed as foreign body granuloma (FBG) with no malignancy. Case 2 was a 78-year-old woman who was diagnosed with axillary lymph node metastases of operated lung cancer and underwent lymphadenectomy and postoperative radiotherapy. No subcutaneous tumor was seen at the beginning of radiotherapy. However, a small nodule appeared in the radiation field at 40 Gy, and it had grown to 30 mm in diameter at 70 Gy. The biopsy specimen was diagnosed as FBG, showing granulation because of a remnant of surgical suture. Both FBGs disappeared within 3–6 months after radiotherapy. In cases in which a tumor has arisen from a site where surgical treatment had been performed and the tumor shows unnatural growth despite radiotherapy, FBG should be considered in the differential diagnosis.     

Stereotactic body radiotherapy for adrenal oligometastasis in lung cancer patients

Objective:To report our experience on stereotactic body radiotherapy (SBRT) in adrenal metastases from lung cancer.Methods:37 oligometastatic lung cancer patients with 38 adrenal metastases submitted to SBRT were retrospectively analyzed. SBRT was delivered by volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT). Primary study end point was local recurrence-free survival (LR-FS) and secondary end points were distant-progression free survival (d-PFS) and overall survival (OS).Results:Median age was 67 years and primary tumor was non-small-cell lung cancer in 27 (73%) and small-cell lung cancer in 10 (27%) patients. Adrenal metastases were in the left side in 66% cases. Median prescribed dose was 30 Gy in 5 fractions for a median biologically equivalent dose (α/β ratio 10  Gy, BED10) of 48 Gy. Most patients (62%) were submitted to SBRT alone, while the others (38%) received chemo-, immune- or target- therapies. Median follow-up was 10.5 months, median OS 16 months and median d-PFS 3 months. 27 (70%) patients obtained a local control with a median LR-FS of 32 months. LR-FS was significantly related to BED10 with a better LC with BED10 ≥72 Gy, 1- and 2 year LR-FS rates were 54.1±11.6% and 45±12.7% vs 100 and 100% for BED ≤59.5 Gy and BED ≥72 Gy, respectively (p = 0.05). There was no severe toxicity.Conclusion:SBRT was effective and safe in lung cancer adrenal metastases. A dose–response relationship was found between BED10 >72 Gy and better local control. No significant toxicity was registered thanks to the respect of dose constraints and suspension of chemo- and target-therapies.Advances in knowledge:SBRT with a BED10 >72 Gy is an effective treatment for adrenal oligometastatic lung cancer patients.     

Magnetic resonance image-guided adaptive stereotactic body radiotherapy for prostate cancer: preliminary results of outcome and toxicity

Objective:Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our preliminary results on the clinical utilization of MRI-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate-specific antigen (PSA) response.Methods:50 prostate cancer patients treated with ultra-hypofractionation were included in the study. Treatment was performed with intensity-modulated radiation therapy (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in 5 fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response.Results:The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade 1 and Grade 2 was 28 and 36%, respectively. Only 6% of patients had acute Grade 1 gastrointestinal (GI) toxicity and there was no Grade ≥ 2 GI toxicity. To date, late Grade 1 GU toxicity was experienced by 24% of patients, 2% of patients experienced Grade 2 GU toxicity and 6% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort.Conclusion:In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile.Advances in knowledge:MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.     

White matter changes on magnetic resonance imaging following whole-brain radiotherapy for brain metastases

Purpose The purpose of this study was to evaluate white matter (WM) abnormalities induced by WBRT. Materials and methods Twenty-four patients (11 men and 13 women; age range 38–74 years, median 60 years) who survived for more than 1 year after completion of WBRT (radiation dose range 30–40 Gy, median 35 Gy) at our institution between January 2000 and June 2003 were followed up with magnetic resonance (MR) scans for 11–51 months (median 19 months). We evaluated WM changes attributable to WBRT as grade 0–6 and assessed possible contributing factors by statistical analysis. Results WM changes were found in 20 patients: Eight were assessed as grade 2, three as grade 3, and nine as grade 5. In total, 12 patients developed grade 3 or higher WM changes. Age (<60 vs ≥60 years), sex, radiation dose (≤35 vs >35 Gy), chemotherapy (with CDDP vs without CDDP), biologically effective dose (≤120 vs >120 Gy1), and head width (<16.3 vs ≥16.3 cm) were found not to be relevant to the incidence or severity of the WM changes. Conclusion Long-term survivors who have under-gone WBRT may have a higher incidence of WM abnormalities.     

Simple method of stereotactic radiotherapy without stereotactic body frame for extracranial tumors

Thirty-five patients with metastatic lung cancer(46 lesions) and twenty patients with primary lung cancer (21 lesions) have been treated with a simple method of stereotactic radiotherapy (SRT) without stereotactic body frame. Tumor size ranged from 1-4 cm in diameter. We used Vac-Lok cushion(Med-Tek) as a immobilization system. To be sure to include the respiratory movement of tumor to planning target volume(PTV), every patients were examined by fluoroscopy and radio-opaque catheters with the same length of tumor movement were attached on the anterior and lateral chest wall before CT simulation. A gold grain was implanted into a tumor that was invisible on fluoroscopy, as a radiomaker. Protocol of 60 Gy/8 fractions/2 weeks and 45 Gy/3 fractions/3-6 days were mainly used. The median follow-up period was 15 months for primary lung cancer and 19 months for metastatic lung cancer. Local control rates were 91% for metastatic lung cancer, 89% for primary lung cancer and 85% for T1, 2N0M0 cases. All patients developed mild pneumonitis or fibrosis about 4.5 months after SRT just in the treatment volume. Only three patients was symptomatic.     

High-dose-rate brachytherapy for previously irradiated patients with recurrent esophageal cancer

Purpose Our objective was to assess the feasibility, efficacy, and complications of high-dose-rate (HDR) brachytherapy for patients with recurrent esophageal cancer after external radiotherapy. Materials and methods Six patients with recurrent esophageal cancer after external radiotherapy were treated with HDR brachytherapy (Ir-192 source) from January 2003 to February 2004. The median age of the patients was 69 years. All patients had received external radiotherapy (median dose 60 Gy) before HDR brachytherapy. All patients underwent HDR brachytherapy once a week with a dose of 4 or 5 Gy per fraction in the esophageal mucosa (median total dose 20 Gy). The Kaplan-Meier method was used to calculate local control rates. Results The median overall survival period was 30.0 months. Local control was observed in five patients and residual tumor in one patient. Persistent local control was observed in two patients. No patient died of esophageal cancer, and all patients survived. We observed no severe late complications related to HDR brachytherapy. Conclusion These data suggest that HDR brachytherapy is an effective and safe treatment for patients with recurrent esophageal cancer after external radiotherapy.     

Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

Purpose

To identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors.

Materials and methods

Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48?C60?Gy (mean 50.1?Gy) in 4?C5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using ¹⁸F-fluoro-2-deoxy-d-glucose, and SBRT doses.

Results

Follow-up time was 1?C60?months (median 18?months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77?%, respectively. On univariate analysis, metastatic tumors (p?p?=?0.0246), and higher SBRT doses (p?=?0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p?=?0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50?%, respectively.

Conclusions

A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT.     

Evaluating proton stereotactic body radiotherapy to reduce chest wall dose in the treatment of lung cancer

Stereotactic body radiotherapy (SBRT) can produce excellent local control of several types of solid tumor; however, toxicity to nearby critical structures is a concern. We found previously that in SBRT for lung cancer, the chest wall (CW) volume receiving 20, 30, or 40 Gy (V₂₀, V₃₀, or V₄₀) was linked with the development of neuropathy. Here we sought to determine whether the dosimetric advantages of protons could produce lower CW doses than traditional photon-based SBRT. We searched an institutional database to identify patients treated with photon SBRT for lung cancer with tumors within < 2.5 cm of the CW. We found 260 cases; of these, chronic grade ≥ 2 CW pain was identified in 23 patients. We then selected 10 representative patients from this group and generated proton SBRT treatment plans, using the identical dose of 50 Gy in 4 fractions, and assessed potential differences in CW dose between the 2 plans. The proton SBRT plans reduced the CW doses at all dose levels measured. The median CW V₂₀ was 364.0 cm³ and 160.0 cm³ (p < 0.0001), V₃₀ was 144.6 cm³ vs 77.0 cm³ (p = 0.0012), V₃₅ was 93.9 cm³ vs 57.9 cm³ (p = 0.005), V₄₀ was 66.5 cm³ vs 45.4 cm³ (p = 0.0112), and mean lung dose was 5.9 Gy vs 3.8 Gy (p = 0.0001) for photons and protons, respectively. Coverage of the planning target volume (PTV) was comparable between the 2 sets of plans (96.4% for photons and 97% for protons). From a dosimetric standpoint, proton SBRT can achieve the same coverage of the PTV while significantly reducing the dose to the CW and lung relative to photon SBRT and therefore may be beneficial for the treatment of lesions closer to critical structures.     

Improved trigeminal and facial nerve tolerance following fractionated stereotactic radiotherapy for large acoustic neuromas

The purpose of this study was to demonstrate improved cranial nerve tolerance following fractionated stereotactic radiotherapy for large acoustic neuromas, defined as tumours with pons-petrous distance (A) > 1 cm and midporous transverse diameter (A + Y) > 2 cm. Of 28 patients with acoustic neuromas treated with fractionated stereotactic radiotherapy, 19 had large tumours at high risk for radiosurgery-induced cranial neuropathy. Six patients received 36 Gy in six, weekly, fractions and 13 patients received 30 Gy in six, weekly, fractions. 15 patients had evaluable trigeminal nerve function and 16 had evaluable facial nerve function. At a median follow-up of 4.5 years, tumour shrinkage was seen in 10 patients and tumour size was stable in nine. None of the patients developed any evidence of transient, or permanent, trigeminal or facial neuropathy at any time during their follow-up period. Fractionated stereotactic radiotherapy may offer a superior therapeutic ratio to single fraction stereotactic radiosurgery in the management of large acoustic neuromas, as evidenced by the absence of post-treatment trigeminal and facial neuropathy.     

36例老年非小细胞肺癌患者三维适形放疗的疗效观察

目的 观察三维放射治疗(3D-CRT)治疗老年非小细胞肺癌患者的疗效和副反应.方法 2001年8月～2006年10月,应用3D-CRT技术治疗70岁以上非小细胞肺癌患者36例.以Leibinger三维放疗计划系统制订放疗计划,处方剂量为40～80Gy(中位剂量60Gy).其中采用低分割照射者24例,单次分割剂量5～8Gy,隔日照射,共8～12次照射;常规分割者12例,共30～40次照射.观察所有患者的肿瘤反应率,1、2年的生存率及治疗毒副作用.结果 33例患者治疗后临床症状获得改善,3例无变化.肿瘤获得完全缓解8例,部分缓解22例,肿瘤总反应率83.33%(30/36).全组生存时间为2～53个月,中位生存时间8个月,1年生存率66.67%,2年生存率36.11%.无严重并发症.结论 对于老年非小细胞肺癌患者,3D-CRT技术是一种安全有效的治疗手段,能够改善生存质量,提高生存率.     

Transpulmonary chemoembolization (TPCE) as a treatment for unresectable lung metastases

To evaluate tumor response after treating unresectable lung metastases with transpulmonary chemoembolization (TPCE) in palliative intention. From 2001 to 2005, 52 patients (mean: 59.8 years; 32 males/20 females) suffering from 106 unresectable lung metastases (mean:6 metastases/patient; range,1–21) were treated with 2–10 TPCE-sessions (mean: 3.3 sessions/patient). Metastases originated from primaries, including colorectal carcinoma (n = 20), breast cancer (n = 6), renal cellular carcinoma (n = 5), thyroid cancer (n = 4), cholangiocellular carcinoma (n = 2), leiomyosarcoma (n = 2), and others (n = 13). Tumor-feeding pulmonary arteries were selectively probed after puncturing the femoral vein, and administering 10 ml lipiodol, mitomycin C, and microspheres (Spherex) each via balloon catheter over pulmonary approach. During therapy, follow-up was accomplished at 4-week intervals using unenhanced and contrast-enhanced CT. After sequential therapy, follow-up was performed every 3 months for a period of 6 months up to 2.25 years. All patients tolerated the treatments well without major side effects or complications. In 24% (n = 13) moderate to high lipiodol uptake was found, while 75% (n = 39) of the tumors showed a low uptake. According to the RECIST criteria, “partial response” was achieved in 16 cases, “stable disease” in 11 cases, and “progressive disease” in 25 cases [mean survival: 17 months/median: 21.1 months (Kaplan-Meyer)]. According to these findings, TPCE is a well-tolerated procedure for palliative treatment of unresectable lung metastases.     

Radiation-induced myositis mimicking chest wall tumor invasion in two patients with lung cancer: a PET/CT study

Two patients with lung cancer who had undergone stereotactic body radiation therapy (SBRT) exhibited increased F-18 FDG uptake in the chest wall after 6 months and 18 months, respectively, after SBRT. The prescribed dose of 50 Gy to the planning target volume was delivered on 4 consecutive days in each patient. It is important for nuclear medicine physicians to be familiar with F-18 FDG PET/CT findings ascribed to radiation-induced myositis in lung cancer patients treated with SBRT so that an appropriate differential diagnosis can be established.     

Radiation injury of the lung after stereotactic body radiation therapy (SBRT) for lung cancer: A timeline and pattern of CT changes

Stereotactic body radiation therapy (SBRT) is a new radiotherapy treatment method that has been applied to the treatment of Stage I lung cancers in medically inoperable patients, with excellent clinical results. SBRT allows the delivery of a very high radiation dose to the target volume, while minimizing the dose to the adjacent normal tissues. As a consequence, CT findings after SBRT have different appearance, geographic extent and progression timeline compared to those following conventional radiation therapy for lung cancer. In particular, SBRT-induced changes are limited to the “shell” of normal tissue outside the tumor and have a complex shape. When SBRT-induced CT changes have a consolidation/mass-like appearance, the differentiation from tumor recurrence can be very difficult. An understanding of SBRT technique as it relates to the development of SBRT-induced lung injury and familiarity with the full spectrum of CT manifestations are important to facilitate diagnosis and management of lung cancer patients treated with this newly emerging radiotherapy method.     

Prognostic factors in stereotactic body radiotherapy of lung metastases

Purpose

The aim of this study was to evaluate prognostic factors in patients with lung metastases who undergo lung stereotactic body radiotherapy (SBRT).

Materials and methods

A total of 87 patients with 129 lung metastases who underwent SBRT between November 2004 and May 2012 were enrolled in this retrospective study. The patient collective consisted of 54 men (62.1%) and 33 women (37.9%); the median age was 65 years (range 36–88). The Karnofsky performance index was ≥70% (median 90%) for all cases, but one (60%). Adverse effects were categorized using the CTCAE 4.0 classification system. Retrospective analyses regarding patients’ characteristics, progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS), and local tumor control rates (LTC) were performed.

Results

On univariate and multivariate analysis OS, DSS, and PFS were significantly (p?<?0.05) better for patients with ≤3 lung metastases; no extrathoracic metastases at the time of the SBRT; a gross tumor volume (GTV) <7.7?cm³ and patients that received a staging that included positron emission tomography with fluorine 18 fluorodeoxyglucose/computed tomography (FDG-PET/CT) imaging. Furthermore, a longer OS was observed if newly diagnosed metastases during follow-up were limited to the lung (median survival: 43.7 months versus 21.7 months; p?=?0.023).

Conclusion

The number and pattern of metastases, and the size of the target volume are strong predictors for the outcome of patients receiving SBRT of lung tumors. FDG-PET/CT should be part of pretherapeutic staging before SBRT.

     

DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily

Background

While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥?60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid).

Patients and methods

Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70?%) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for <??2.5 cm, 79.2 Gy for 2.5–4.5 cm, 84.6 Gy for 4.5–6 cm, 90 Gy for >?6 cm.

Results

The median follow-up was 28.5 months (range 2–108 months); actuarial local control (LC) at 2 and 3 years was 88?%, while regional control was 100?%. There were 10 patients (19?%) who died of the tumor, and 18 patients (33?%) died due to cardiovascular or pulmonary causes. A total of 11 patients (20?%) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28?%) are alive. Acute esophagitis ≤??grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis.

Conclusion

DART-bid yields high LC without significant toxicity. For centrally located and/or large (>?5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts.

     

Assessment of treatment response after lung stereotactic body radiotherapy using diffusion weighted magnetic resonance imaging and positron emission tomography: A pilot study

Background and purposeThere is no early predictor of treatment response after lung stereotactic body radiotherapy (SBRT). We conducted this pilot study to evaluate whether serial diffusion weighted magnetic resonance imaging (DW-MRI) or positron emission tomography (PET) could predict response after SBRT.Material and methodsEarly stage non-small cell lung cancer patients who received SBRT were eligible. DW-MRI and PET were undertaken pretreatment and every 3 months after SBRT in the first year. Patients with <1 year of follow-up were excluded from the analysis. The apparent diffusion coefficient (ADC) value and maximum standardized uptake value (SUV_max) of tumors were measured and compared between groups with or without local recurrence (LR).ResultsFifteen patients were enrolled and the data of 14 patients were analyzed. The median ADC value was significantly lower in patients with LR (n = 3) than in those without LR (n = 11) at 3 and 6 months (1.11 vs. 1.54 and 0.98 vs. 1.69 [×10⁻³ mm²/s]; p = 0.039 and 0.012, respectively) while there was no significant difference pretreatment and at 9 and 12 months after treatment. No significant difference was observed in the SUV_max at any time point.ConclusionsDW-MRI could be an early predictor of treatment response after lung SBRT.