Five-year outcomes following hypofractionated stereotactic radiotherapy delivered in five fractions for acoustic neuromas: the mean cochlear dose may impact hearing preservation.

BACKGROUND: The aim of this study was to assess the clinical outcomes of acoustic neuromas (ANs) treated with hypofractionated stereotactic radiotherapy (hypo-FSRT) prescribed at a uniform dose. METHODS: Forty-seven patients with a unilateral AN were treated consecutively with hypo-FSRT between February 2007 and March 2012. Nineteen patients maintained a serviceable hearing status at the beginning of hypo-FSRT. The prescribed dose was 25 Gy delivered in five fractions per week to the isocenter, and the planning target volume was covered by the 80% isodose line. RESULTS: The median follow-up and audiometric follow-up periods were 61 and 52 months, respectively. The estimated tumor control rate at 5 years was 90% (95% CI 76-96). The existence of the cystic component before hypo-FSRT had a significantly worse impact on tumor control (p = 0.02). The estimated hearing preservation rates at 1, 3 and 5 years were 68% (95% CI 42-84), 41% (95% CI 20-62) and 36% (95% CI 15-57), respectively. A borderline significant difference was identified in the mean biological effective dose with an α/ß value of 3 Gy (BED3) to the ipsilateral cochlea between the preserved hearing and hearing loss groups (19 Gy vs. 28 Gy) (p = 0.08). CONCLUSIONS: Hypo-FSRT delivered in five fractions for unilateral ANs may achieve excellent tumor control with no severe facial or trigeminal complications. The mean BED3 in the cochlea may impact the hearing preservation rate. Therefore, the cochlear dose should be as low as possible.

Feasibility evaluation of hypofractionated radiotherapy with concurrent temozolomide in elderly patients with glioblastoma.

BACKGROUND: Although hypofractionated radiotherapy (HFRT) is preferred to conventionally fractionated radiotherapy when treating elderly patients with glioblastoma, the benefits and tolerability of HFRT with concurrent temozolomide (TMZ) remain unknown for such patients. We assessed the feasibility and outcomes of elderly patients with glioblastoma treated with HFRT and concurrent TMZ. METHODS: We retrospectively reviewed the medical records of 11 patients aged ≥70 years who were treated with HFRT and concurrent TMZ. All patients had newly diagnosed and histologically confirmed glioblastoma and were treated at our institution between October 2011 and April 2015. The median age was 74 years (range, 70-85 years). Total resection/subtotal resection/biopsy were performed in 2/5/4 patients, respectively. The planning target volume included the T1-enhancing tumor and the resection cavity plus 2-cm margins, and all surrounding edema. The median prescription dose was 35 Gy (range, 35-42.5 Gy), delivered in 10 fractions. Seven patients received TMZ at 150 mg/m2 for 5 days and 4 received TMZ at 75 mg/m2 during HFRT. Overall survival (OS) was defined as the time from surgery to death or the last follow-up. RESULTS: The median follow-up period was 13.2 months. The median OS and progression-free survival (PFS) times were 13.2 and 7.0 months, respectively. One patient experienced grade 4 neutropenia, lymphocytopenia, and thrombocytopenia. No grade 3 or higher nonhematological adverse event was noted. CONCLUSION: Our analysis demonstrated the feasibility of HFRT with concurrent TMZ used to treat elderly patients with glioblastoma. Further prospective clinical trials are needed to define therapies that balance efficacy with tolerability.

Dosimetric advantages of O-ring design radiotherapy system for skull-base tumors.

The purpose of this study was to investigate whether a new O-ring design radiotherapy delivery system has advantages in radiotherapy planning for skull-base tumors. Twenty-five patients with skull-base tumors were included in this study. Two plans were made using conventional (Plan A) or new (Plan B) techniques. Plan A consisted of four dynamic conformal arcs (DCAs): two were horizontal, and the other two were from cranial directions. Plan B was created by converting horizontal arcs to those from caudal directions making use of the O-ring design radiotherapy system. The micromultileaf collimators were fitted to cover at least 99% of the planning target volume with prescribed doses, 90% of the dose at the isocenter. The two plans were compared in terms of target homogeneity, conformity, and irradiated volume of normal tissues, using a two-sided paired t-test. For evaluation regarding target coverage, the homogeneity indices defined by the International Commission on Radiation Units and Measurements 83 were 0.099 ± 0.010 (mean ± standard deviation) and 0.092 ± 0.010, the conformity indices defined by the Radiation Therapy Oncology Group were 1.720 ± 0.249 and 1.675 ± 0.239, and the Paddick's conformity indices were 0.585 ± 0.078 and 0.602 ± 0.080, in Plans A and B, respectively. For evaluation of irradiated normal tissue, the Paddick's gradient indices were 3.118 ± 0.283 and 2.938 ± 0.263 in Plans A and B, respectively. All of these differences were statistically significant (p-values < 0.05). The mean doses of optic nerves, eyes, brainstem, and hippocampi were also significantly lower in Plan B. The DCA technique from caudal directions using the new O-ring design radiotherapy system can improve target homogeneity and conformity compared with conventional DCA techniques, and can also decrease the volume of surrounding normal tissues that receives moderate doses.

Recurrence-free survival and prognosis after adjuvant therapy with radioactive iodine-131 in patients with differentiated thyroid carcinoma.

This study aimed to assess recurrence-free survival (RFS) rates and recurrence-related factors of patients who received adjuvant therapy (AT) with radioactive iodine (RAI) for differentiated thyroid cancer (DTC) following thyroidectomy. We evaluated 284 patients who underwent AT between January 2011 and July 2020 at our hospital. Recurrence was defined as visible recurrent lesions on image analysis or need for repeat surgery with pathologically confirmed recurrent lesions. RFS rate and prognostic factors were statistically evaluated. The median observation period was 30.2 months (range, 5.7-294 months). Overall, 192 patients were female and 92 were male, and the median age was 54 years (range, 9-85 years). Initial assessment revealed 39 recurrence cases. The 3-year RFS rate was 85.8% (95% confidence interval: 81.1-90.9%). Univariate analysis revealed that histology (except for papillary carcinoma), Tg level > 4 ng/dL before AT, and AT result significantly exacerbated the RFS rate. In multivariate analysis, histology and AT result were also important contributors to the worsening RFS rate. Results of AT can be determined relatively early and are important in predicting future recurrence in patients with DTC. Increasing the success rate of AT may lead to an improved prognosis.

Outcomes of hypofractionated stereotactic radiotherapy for metastatic brain tumors with high risk factors.

The present study aimed to analyze outcomes of hypofractionated stereotactic radiotherapy (HFSRT) delivered in five fractions to metastatic brain tumors. Between June 2008 and June 2011, 39 consecutive patients with 46 brain metastases underwent HFSRT at Kyoto University Hospital. Selection criteria included high risk factors such as eloquent location, history of whole-brain radiotherapy (WBRT), or large tumor size. Given these factors, fractionated schedules were preferable in terms of radiobiology. The prescribed dose at the isocenter was basically 35 Gy in five fractions. Brainstem lesions with a history of WBRT were treated with 20-25 Gy in five fractions. Planning target volume was covered by the 80 % isodose line of the prescribed dose to the isocenter. Local-control probability and overall survival were estimated using the Kaplan-Meier method. For the analysis of local control, the response criteria were defined as follows: complete response (CR) was defined as no visible gross tumor or absence of contrast enhancement, partial response (PR) as more than a 30 % decrease in size, progressive disease as more than a 20 % increase in size, and stable disease (SD) as all other responses. Local control was defined as a status of CR, PR, or SD. Only patients with at least 3 months or longer follow-up (21 patients, 27 tumors) were included in the analysis. Median age and Karnofsky performance status were 59 years (range, 39-84 years) and 90 (range, 40-100), respectively. Tumor volumes and maximum diameters ranged from 0.08 to 15.38 cm(3) (median, 3.67 cm(3)) and from 3 to 34 mm (median, 18 mm), respectively. The median follow-up period was 329 days (range, 120-1,321 days). Local-control probabilities at 6 and 12 months were 92.1 and 86.7 %, respectively. Overall survival after HFSRT at 6 and 12 months was 85.4 and 64.5 %, respectively. Grade 3 radiation necrosis was observed in one patient according to the Common Terminology Criteria for Adverse Events version 3.0. The patient was successfully managed conservatively. HFSRT for metastatic brain tumors yields high local-control probabilities without increasing severe adverse events despite high risk factors.

Interfractional target changes in brain metastases during 13-fraction stereotactic radiotherapy.

BACKGROUND: The risk for radiation necrosis is lower in fractionated stereotactic radiotherapy (SRT) than in conventional radiotherapy, and 13-fraction SRT is our method of choice for the treatment of brain metastases ≥ around 2 cm or patients who are expected to have a good prognosis. As 13-fraction SRT lasts for at least 17 days, adaptive radiotherapy based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) is often necessary for patients undergoing 13-fraction SRT. In this study, we retrospectively analyzed interfractional target changes in patients with brain metastases treated with 13-fraction SRT. METHODS: Our analyses included data from 23 patients and 27 metastatic brain lesions treated with 13-fraction SRT with dynamic conformal arc therapy. The peripheral dose prescribed to the planning target volume (PTV) was 39-44.2 Gy in 13-fractions. The gross tumor volume (GTV) of the initial SRT plan (initial GTV), initial PTV, and modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were assessed. RESULTS: The median initial GTV was 3.8 cm3 and the median time from SRT initiation to the mid-treatment MRI scan was 6 days. Compared to the initial GTV, the mid-treatment GTV increased by more than 20% in five lesions and decreased by more than 20% in five lesions. Interfractional GTV volume changes of more than 20% were not significantly associated with primary disease or the presence of cystic components/necrosis. The mid-treatment GTV did not overlap perfectly with the initial PTV in more than half of the lesions. CONCLUSIONS: Compared to the initial GTV, the mid-treatment GTV changed by more than 20% in almost one-third of lesions treated with 13-fraction SRT. As SRT usually generates a steep dose gradient as well as increasing the maximum dose of PTV compared to conventional radiotherapy, assessment of the volume and locational target changes and adaptive radiotherapy should be considered as the number of fractions increases.

Comparison of thyroid hormone withdrawal and recombinant human thyroid-stimulating hormone administration for adjuvant therapy in patients with intermediate- to high-risk differentiated thyroid cancer.

OBJECTIVE: To compare the clinical outcome in patients who received adjuvant therapy with radioactive iodine (RAI) using different preparation methods, namely, thyroid hormone withdrawal (THW) and recombinant human thyroid-stimulating hormone (rhTSH), after undergoing thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma (DTC) according to the American Thyroid Association criteria. METHODS: Between May 2012 and October 2018, 136 patients who underwent adjuvant therapy with high-dose (3700 MBq) RAI for DTC without any metastatic lesions or macroscopic residual lesions after surgical resection were retrospectively selected. Patients were excluded if distant metastasis was confirmed during adjuvant therapy or if the outcome could not be confirmed; thus, 112 patients were finally evaluated. Patients underwent either a 3-week I restriction with thyroxine withdrawal or a 2-week I restriction with rhTSH administration. The serum thyroglobulin (Tg) concentration was measured, and 131I scintigraphy (370 MBq) was performed 6-12 months after adjuvant therapy. The definition of the initial achievement of adjuvant therapy was the disappearance of the uptake of 131I at the thyroid bed and serum Tg concentration < 2.0 ng/mL. The results of the adjuvant therapy between the groups were compared using the Fisher's exact test, and the TSH levels and estimated glomerular filtration rate (eGFR) were compared using the Welch's t test. RESULTS: The THW and rhTSH groups included 47 and 65 patients, respectively, and the intermediate- and high-risk groups included 63 and 49 patients, respectively. No patient was assigned to the low-risk group. In the THW and rhTSH groups, the initial RAI adjuvant therapy goal was achieved in 30/47 (63.8%) and 46/65 patients (70.8%), respectively (p = 0.54); mean ± standard deviation of the TSH levels was 123.8 ± 46.4 µIU/mL and 274.5 ± 97.7 µIU/mL, respectively (p < 0.01), and eGFR (treatment/pre-treatment) was 0.81 and 0.99, respectively (p < 0.01). In the intermediate- and high-risk groups, the initial RAI adjuvant therapy goal was achieved in 43/63 patients (68.3%) and 33/49 (67.3%), respectively (p = 1.0). CONCLUSION: No significant differences were observed between the preparation methods in the initial achievement of RAI adjuvant therapy. However, patients in the rhTSH group demonstrated higher TSH levels and retained eGFR.

Difficulty in distinguishing radiation-induced prostate sarcoma from radiation mucositis in a patient with persistent urinary retention and hematuria after prostate cancer radiotherapy.

Urinary retention and hematuria owing to radiation-induced mucositis are occasional late adverse events in patients with prostate cancer. Moreover, radiation-induced secondary malignancies are late adverse events, although they are extremely rare. Herein, we describe a case of radiation-induced secondary malignancy of the prostate that was initially difficult to distinguish from radiation mucositis. A 74-year-old man with prostate cancer underwent brachytherapy and external beam radiotherapy 9 years ago. Twenty-eight months after irradiation, he presented with urinary retention and hematuria owing to radiation mucositis and underwent transurethral resection of the prostate. At 89 months after irradiation, the patient again showed urinary retention and hematuria. The cause of urinary retention and hematuria could not be identified on cystoscopy. Despite receiving medications, the patient's symptoms did not improve. Therefore, transurethral fulguration was performed, and prostate biopsy revealed spindle cell sarcoma. A diagnosis of radiation-induced undifferentiated pleomorphic/spindle cell sarcoma was made, and the patient underwent total cystectomy and construction of the ileal conduit. Two weeks after the surgery, computed tomography revealed peritoneal dissemination. The patient died 5 weeks after the surgery. The case findings indicate that clinicians should consider the possibility of radiation-induced secondary malignancy; moreover, thorough pathological examination of the prostate with CT and MRI is important to distinguish RISM from radiation mucositis even if no tumors are found on cystoscopy.

Comparison between the different doses of radioactive iodine ablation prescribed in patients with intermediate-to-high-risk differentiated thyroid cancer.

OBJECTIVE: This study aimed to compare the clinical outcomes of patients who received radioactive iodine (RAI) ablation after undergoing thyroidectomy for intermediate-to-high-risk differentiated thyroid carcinoma (DTC) according to the American Thyroid Association (ATA) criteria. METHODS: We retrospectively examined patients who underwent RAI ablation for DTC after surgical resection without macroscopic residual lesions or metastatic lesions between December 2011 and August 2016. Among 147 patients who underwent RAI ablation, those whose initial pathological stages or RAI ablation results were unknown and whose distant metastases were confirmed during RAI ablation were excluded. Low-dose therapy was defined as administration of 1110 MBq of 131iodine (131I), while high-dose therapy referred to administration of 2960-3700 MBq of 131I. We defined initial success of RAI ablation as a serum thyroglobulin concentration of < 2.0 ng/mL without thyroid-stimulating hormone stimulation and disappearance of 131I uptake in the thyroid bed on 131I scintigraphy 6-12 months after RAI ablation. RAI ablation success rates were compared between the low-dose and high-dose groups using Fisher's exact test, and inverse probability of treatment weighting (IPTW) analysis was performed for adjusting potential biases. RESULTS: Among the 119 patients examined in this study (39 men and 80 women), 79 were classified as having intermediate risk, while 40 were classified as having high risk based on the ATA guideline. Initial RAI ablation success was achieved in 50/68 (73.5%) patients from the low-dose group and in 36/51 patients (70.6%) from the high-dose group (p = 0.84). Moreover, IPTW analysis showed no significant difference between the low-dose and high-dose groups. However, the success rate tended to be superior in high-risk patients who received high-dose therapy (86.2%) than in those who received low-dose therapy (72.7%) (p = 0.37). CONCLUSION: There was no significant difference in the RAI ablation success rate between the low-dose and high-dose groups involving patients with intermediate-to-high-risk DTC. However, high-dose RAI ablation may be recommended in high-risk patients.

Single-isocenter volumetric-modulated Dynamic WaveArc therapy for two brain metastases.

PURPOSE: A new irradiation technique, volumetric-modulated Dynamic WaveArc therapy (VMDWAT), based on sequential non-coplanar trajectories, can be performed using the Vero4DRT. This planning study compared the dose distribution and treatment time between single-isocenter volumetric-modulated arc therapy (VMAT) with multiple straight non-coplanar arcs and single-isocenter VMDWAT in patients with two brain metastases. MATERIALS AND METHODS: Twenty patients with two planning target volumes exceeding 2.0 cm3 were included. Both VMAT and VMDWAT plans were created with single isocenter and a prescribed dose of 28 Gy delivered in five fractions. Target conformity was evaluated using indices modified from the RTOG-CI (mRTOG-CI) and IP-CI (mIP-CI). RESULTS: VMDWAT significantly improved both mRTOG-CI and mIP-CI and reduced the volume of normal brain tissue receiving 25 and 28 Gy compared to VMAT. The two modalities did not significantly differ in terms of the volume of normal brain tissue receiving 5, 10, 12, 15, and 20 Gy. The mean treatment time was significantly shorter in the VMDWAT group. CONCLUSION: VMDWAT significantly improved dose distribution in a shorter treatment time compared to VMAT in patients treated for two brain metastases. Single-isocenter VMDWAT may thus be a promising treatment for two brain metastases.

Dosimetric comparison between dual-isocentric dynamic conformal arc therapy and mono-isocentric volumetric-modulated arc therapy for two large brain metastases.

Mono-isocentric volumetric-modulated arc therapy (VMAT) can be used to treat multiple brain metastases. It remains unknown whether mono-isocentric VMAT can improve the dose distribution compared with dual-isocentric dynamic conformal arc therapy (DCAT), especially for two brain metastases. We compared the dose distribution between dual-isocentric DCAT and mono-isocentric VMAT for two large brain metastases, and analyzed the relationship between the distance between the two targets and the difference in dose distribution. A total of 19 patients, each with two large brain metastases, were enrolled. The dose prescribed for each planning target volume (PTV) was 28 Gy in five fractions (D99.8 = 100%). We created new indices derived from conformity indices suggested by the Radiation Therapy Oncology Group (RTOG; mRTOG-CI) and Paddick et al. (mIP-CI), using the dosimetric parameters of the sum of the two PTVs. The median PTV was 5.05 cm3 (range, 2.10-28.47). VMAT significantly improved mRTOG-CI and mIP-CI compared with DCAT. In all cases, VMAT was able to improve mRTOG-CI and mIP-CI compared with DCAT. Whereas the normal brain volume receiving 5 Gy was similar between the two modalities, the normal brain receiving 10, 12, 15, 20, 25 and 28 Gy (V10-V28) was significantly smaller in VMAT. The mean beam-on times were 213.3 s and 121.9 s in DCAT and VMAT, respectively (P < 0.001). Mono-isocentric VMAT improved the target conformity and reduced the beam-on time and V10-V28 of the normal brain for not only two close metastases but also two distant metastases. Mono-isocentric VMAT seems to be a promising treatment technique for two large brain metastases.

Volumetric modulated Dynamic WaveArc therapy reduces the dose to the hippocampus in patients with pituitary adenomas and craniopharyngiomas.

PURPOSE: Reducing the radiation dose to the hippocampus is important to preserve cognitive function in patients with brain tumors. The Vero4DRT system can realize a new irradiation technique, termed volumetric-modulated Dynamic WaveArc therapy (VMDWAT), which allows the safe use of sequential noncoplanar volumetric-modulated beams without couch rotation. Because VMDWAT appears to reduce the hippocampal dose in patients with pituitary adenomas and craniopharyngiomas, we performed a planning study to compare the dose distribution of volumetric-modulated arc therapy using only a coplanar arc (coVMAT) and VMDWAT. METHODS AND MATERIALS: CoVMAT and VMDWAT plans were created for 30 patients with pituitary adenomas and craniopharyngiomas. The prescription dose was 52.2 Gy in 29 fractions, with 99% of each planning target volume covered by 90% of the prescribed dose. Optimization was performed for maximal reduction of the dose to the hippocampus. Treatment time was defined as the beam-on time. RESULTS: The mean equivalent dose in 2 Gy fractions to 40% of the volume of the bilateral hippocampus (EQD40%) for coVMAT/VMDWAT were 9.90/5.31 Gy, respectively (P < .001). The mean EQD40% in VMDWAT was less than 7.3 Gy, which is the threshold for predicting cognitive impairment. Although the volume of normal brain receiving 5 Gy (V5) was significantly larger in VMDWAT, compared with coVMAT, the normal brain volume receiving 10, 15, 20, 25, 30, 35, 40, 45, and 50 Gy (V10-50) was significantly smaller in VMDWAT. The conformity and homogeneity indices were significantly better in VMDWAT. The mean VMDWAT treatment time was longer compared with coVMAT (70.1 vs 67.1 seconds, respectively). CONCLUSIONS: Although VMDWAT increased brain V5 and the treatment time compared with coVMAT, it significantly reduced the dose to the hippocampus and brain V10 to V50 and improved target conformity and homogeneity. VMDWAT could be a promising treatment technique for pituitary adenomas and craniopharyngiomas.

Modifying the planning target volume to optimize the dose distribution in dynamic conformal arc therapy for large metastatic brain tumors.

PURPOSE: When treating large metastatic brain tumors with stereotactic radiotherapy (SRT), high dose conformity to target is difficult to achieve. Employing a modified planning target volume (mPTV) instead of the original PTV may be one way to improve the dose distribution in linear accelerator-based SRT using a dynamic conformal technique. In this study, we quantitatively analyzed the impact of a mPTV on dose distribution. MATERIALS AND METHODS: Twenty-four tumors with a maximum diameter of >2 cm were collected. For each tumor, two plans were created: one used a mPTV and the other did not. The mPTV was produced by shrinking or enlarging the original PTV according to the dose distribution in the original plan. The dose conformity was evaluated and compared between the plans using a two-sided paired t test. RESULTS: The conformity index defined by the Radiation Therapy Oncology Group was 1.34 ± 0.10 and 1.41 ± 0.13, and Paddick's conformity index was 0.75 ± 0.05 and 0.71 ± 0.06, for the plans with and without a mPTV, respectively. All of these improvements were statistically significant (P < 0.05). CONCLUSION: The use of a mPTV can improve target conformity when planning SRT for large metastatic brain tumors.

Prevalence of hypothyroidism among patients with breast cancer treated with radiation to the supraclavicular field: a single-centre survey.

PURPOSE: We investigated the prevalence of hypothyroidism (HT) in patients with breast cancer who received radiation therapy to the supraclavicular (SC) field to evaluate the effect of radiation on thyroid. METHODS: Between April 2007 and May 2016, consecutive patients with invasive breast cancer who received SC radiation were recruited. Thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were measured between April and August 2016. On the basis of the radiation-planning CT images, thyroid volume was calculated and dose-volume parameters were estimated. The endpoints were the prevalence of HT as determined by high levels of TSH and low levels of fT4 in serum, and the prevalence of subclinical HT, determined by high-serum TSH and normal fT4. RESULTS: Among the 68 consecutive patients, 26 were excluded from evaluation (10 patients died, 6 had a history of previous thyroid disease and 10 were lost to follow-up). One (2.4%) and six (14.3%) of these patients had HT and subclinical HT, respectively, with a mean TSH level of 8.27 µU/mL. By univariate analysis, a predictive factor of HT and subclinical HT was a thyroid volume <8 cm3 (OR 6.44, 95% CI 1.14 to 36.6; p=0.043). Multivariate analysis also showed an association between thyroid volume <8 cm3 and HT or subclinical HT (OR 18.48, 95% CI 1.48 to 230.86; p=0.024). CONCLUSIONS: The prevalence of HT in patients with breast cancer studied was relatively low. Although thyroid volume appeared to be a predictive marker of HT in this cohort, further prospective evaluation is needed.

Non-coplanar volumetric-modulated arc therapy (VMAT) for craniopharyngiomas reduces radiation doses to the bilateral hippocampus: a planning study comparing dynamic conformal arc therapy, coplanar VMAT, and non-coplanar VMAT.

BACKGROUND: Recent studies suggest that radiation-induced injuries to the hippocampus play important roles in compromising neurocognitive functioning for patients with brain tumors and it could be important to spare the hippocampus using modern planning methods for patients with craniopharyngiomas. As bilateral hippocampus are located on the same level as the planning target volume (PTV) in patients with craniopharyngioma, it seems possible to reduce doses to hippocampus using non-coplanar beams. While the use of non-coplanar beams in volumetric-modulated arc therapy (VMAT) of malignant intracranial tumors has recently been reported, no dosimetric comparison has yet been made between VMAT using non-coplanar arcs (ncVMAT) and VMAT employing only coplanar arcs (coVMAT) among patients with craniopharyngiomas. We performed a planning study comparing dose distributions to the PTV, hippocampus, and other organs at risk (OAR) of dynamic conformal arc therapy (DCAT), coVMAT, and ncVMAT. METHODS: DCAT, coVMAT, and ncVMAT plans were created for 10 patients with craniopharyngiomas. The prescription dose was 52.2 Gy in 29 fractions, and 99 % of each PTV was covered by 90 % of the prescribed dose. The maximum dose was held below 107 % of the prescribed dose. CoVMAT and ncVMAT plans were formulated to satisfy the following criteria: the doses to the hippocampus were minimized, and the doses to the OAR were similar to or lower than those of DCAT. RESULTS: The mean equivalent doses in 2-Gy fractions to 40 % of the volumes of the bilateral hippocampus [EQD2(40%hippos)] were 15.4/10.8/6.5 Gy for DCAT/coVMAT/ncVMAT, respectively. The EQD2(40%hippos) for ncVMAT were <7.3 Gy, which is the threshold predicting cognitive impairment, as defined by Gondi et al.. The mean doses to normal brain tissue and the conformity indices were similar for the three plans, and the homogeneity indices were significantly better for coVMAT and ncVMAT compared with DCAT. CONCLUSIONS: NcVMAT is more appropriate than DCAT and coVMAT for patients with craniopharyngiomas. NcVMAT significantly reduces radiation doses to the bilateral hippocampus (to 50 % that of the DCAT) without increasing the doses to normal brain tissue and other OAR.

Pineal parenchymal tumor of intermediate differentiation: Treatment outcomes of five cases.

Pineal parenchymal tumor of intermediate differentiation (PPTID) is a rare disease, first classified by the World Health Organization in 2000. The number of available studies on the treatment of PPTID is currrently limited and the optimal management for this disease has not yet been determined. We retrospectively evaluated the treatment outcomes for PPTID at our institute and analyzed the roles of radiation therapy and chemotherapy for this disease. The clinical data on five patients diagnosed with PPTID since 2000 were retrospectively reviewed. Patients with cerebrospinal dissemination at diagnosis received biopsy-only surgery, craniospinal and whole-ventricular irradiation and chemotherapy. Patients with locally limited disease at diagnosis received local or whole-ventricular irradiation after surgery. The median relapse-free and overall survival were 72.9 and 94.1 months, respectively. Two of the five patients developed a relapse of cerebrospinal dissemination after treatment and succumbed to the disease. All the patients who received both craniospinal and whole-ventricular irradiation exhibited evidence of cerebral white matter abnormalities in magnetic resonance imaging and developed neurocognitive disorders after treatment. Although PPTID may be aggressive and has cerebrospinal fluid seeding potential, PPTID patients may survive long-term, even after recurrence. Considering the long survival time and the late adverse effects due to intensive treatment, the irradiation field and usage of chemotherapy after surgery require optimization.

Volumetric-modulated arc therapy vs conventional fixed-field intensity-modulated radiotherapy in a whole-ventricular irradiation: a planning comparison study.

This study evaluated the dosimetric difference between volumetric-modulated arc therapy (VMAT) and conventional fixed-field intensity-modulated radiotherapy (cIMRT) in whole-ventricular irradiation. Computed tomography simulation data for 13 patients were acquired to create plans for VMAT and cIMRT. In both plans, the same median dose (100% = 24 Gy) was prescribed to the planning target volume (PTV), which comprised a tumor bed and whole ventricles. During optimization, doses to the normal brain and body were reduced, provided that the dose constraints of the target coverage were satisfied. The dose-volume indices of the PTV, normal brain, and body as well as monitor units were compared between the 2 techniques by using paired t-tests. The results showed no significant difference in the homogeneity index (0.064 vs 0.065; p = 0.824) of the PTV and conformation number (0.78 vs 0.77; p = 0.065) between the 2 techniques. In the normal brain and body, the dose-volume indices showed no significant difference between the 2 techniques, except for an increase in the volume receiving a low dose in VMAT; the absolute volume of the normal brain and body receiving 1 Gy of radiation significantly increased in VMAT by 1.6% and 8.3%, respectively, compared with that in cIMRT (1044 vs 1028 mL for the normal brain and 3079.2 vs 2823.3 mL for the body; p<0.001). The number of monitor units to deliver a 2.0-Gy fraction was significantly reduced in VMAT compared with that in cIMRT (354 vs 873, respectively; p<0.001). In conclusion, VMAT delivers IMRT to complex target volumes such as whole ventricles with fewer monitor units, while maintaining target coverage and conformal isodose distribution comparable to cIMRT; however, in addition to those characteristics, the fact that the volume of the normal brain and body receiving a low dose would increase in VMAT should be considered.

Efficacy of salvage stereotactic radiotherapy for recurrent glioma: impact of tumor morphology and method of target delineation on local control.

In this study, we assessed the efficacy of salvage stereotactic radiotherapy (SRT) for recurrent glioma. From August 2008 to December 2012, 30 patients with recurrent glioma underwent salvage SRT. The initial histological diagnoses were World Health Organization (WHO) grades II, III, and IV in 6, 9, and 15 patients, respectively. Morphologically, the type of recurrence was classified as diffuse or other. Two methods of clinical target delineation were used: A, a contrast-enhancing tumor; or B, a contrast-enhancing tumor with a 3-10-mm margin and/or surrounding fluid attenuation inversion recovery (FLAIR) high-intensity areas. The prescribed dose was 22.5-35 Gy delivered in five fractions at an isocenter using a dynamic conformal arc technique. The overall survival (OS) and local control probability (LCP) after SRT were calculated using the Kaplan-Meier method. A univariate analysis was used to test the effect of clinical variables on OS/LCP. The median follow-up period was 272 days after SRT. The OS and LCP were 83% and 56% at 6 months after SRT, respectively. Morphologically, the tumor type correlated significantly with both OS and LCP (P = 0.006 and <0.001, respectively). The method of target delineation also had a significant influence on LCP (P = 0.016). Grade 3 radiation necrosis was observed in two patients according to Common Terminology Criteria for Adverse Events, version 3. Salvage SRT was safe and effective for recurrent glioma, especially non-diffuse recurrences. Improved local control might be obtained by adding a margin to contrast-enhancing tumors or including increased FLAIR high-intensity areas.

Initial and cumulative recurrence patterns of glioblastoma after temozolomide-based chemoradiotherapy and salvage treatment: a retrospective cohort study in a single institution.

PURPOSE: To analyze initial recurrence patterns in patients with newly diagnosed glioblastoma after radiotherapy plus concurrent and adjuvant temozolomide, and to investigate cumulative recurrence patterns after salvage treatment, including surgery, stereotactic radiotherapy, and chemotherapy. METHODS: Twenty-one patients with glioblastoma that recurred after concurrent temozolomide and localized radiotherapy were retrospectively analyzed (11 male, 10 female; median age, 57 years; range, 27-74). Disease progression was assessed by new response criteria proposed by the Response Assessment in Neuro-Oncology Working Group of the American Society of Clinical Oncology. The pattern of recurrence was determined by relationships between locations of recurrent tumors and irradiated doses. Central, in-field, marginal, and out-field recurrences were defined relative to the prescribed isodose line. Distant recurrence was operationally defined as subependymal or disseminated disease. Initial and cumulative patterns of recurrence were evaluated in each patient. RESULTS: The median follow-up of the recurrent patients was 501 (range, 217-1815) days after initial surgery. Initial recurrences were central in 14 patients (66.7%), in-field in four patients (19.0%), marginal in no patient (0%), out-field in two patients (9.5%), and distant in four patients (19.0%). One patient had both central and in-field recurrences simultaneously, and two had both central and distant recurrences. In the analysis of cumulative recurrence patterns, five patients, who had no scans after initial recurrences, were excluded and the remaining 16 were included. Cumulative recurrences were central in 11 patients (68.8%), in-field in five patients (31.3%), marginal in three patients (18.8%), out-field in five patients (31.3%), and distant in 14 patients (87.5%). Regarding salvage treatments, 11 (52.4%), 11 (52.4%) and 17 (81.0%) patients underwent surgery, stereotactic radiotherapy and chemotherapy, respectively. Eighteen (85.7%) patients had died at the time of analysis, and 16 of them (88.9%) had suffered distant recurrences, which could have been the immediate causes of death. CONCLUSIONS: Recurrence patterns of glioblastoma after radiotherapy plus concomitant and adjuvant temozolomide were mainly central at first, and distant recurrences were often detected during the clinical course. Much better local control and prevention of distant recurrence, including effective salvage treatment, seem to be important.