The importance of preserving the superior hypophyseal artery infundibular branch in craniopharyngioma surgery.

PURPOSE: Postoperative pituitary dysfunction, a critical problem in the treatment of craniopharyngiomas, can occur even when the pituitary stalk is preserved. We hypothesized that compromise of the primary superior hypophyseal artery (pSHA) might be related to this occurrence. METHODS: We performed a retrospective review of 131 patients with craniopharyngioma who underwent surgery from April 2009 to September 2021. The inclusion criteria were initial surgery, endoscopic transsphenoidal surgery, preoperative normal pituitary function or pituitary dysfunction in one axis, and morphological preservation of the pituitary stalk. The branches of the pSHA consist mainly of the chiasmatic branches (Cb), infundibular branches (Ib), and descending branches (Db). We analyzed the association between postoperative pituitary function and preservation of these branches. RESULTS: Twenty patients met the criteria. Preoperative anterior pituitary function was normal in 18 patients, and there was isolated growth hormone deficiency in two patients. No patient had preoperative diabetes insipidus (DI). Anterior pituitary function was unchanged postoperatively in eight patients. Of these eight patients, bilateral preservation of pSHA Ib was confirmed in seven patients. Bilateral preservation of pSHA Ib was the only factor associated with preserved anterior pituitary function (p < 0.01). Fifteen patients were free of permanent DI, and the preservation of any given pSHA branch produced no significant difference in the postoperative occurrence of permanent DI. CONCLUSIONS: Our study shows that bilateral preservation of pSHA Ib provides favorable postoperative anterior pituitary function in craniopharyngioma surgery; however, such preservation may have little effect on the postoperative occurrence of DI.

Direct intracranial invasion of eccrine spiradenocarcinoma of the scalp: a case report and literature review.

BACKGROUND: Eccrine spiradenocarcinoma (SC), also known as malignant eccrine spiradenoma, is a rare malignant cutaneous adnexal neoplasm arising from long-standing benign eccrine spiradenoma. Malignant skin tumors rarely show direct intracranial invasion. However, once the intracranial structure is infiltrated, curative excision with sufficient margins can become extremely difficult, particularly when the venous sinuses are involved. No effective adjuvant therapies have yet been established. Here, we report an extremely rare case of scalp eccrine SC with direct intracranial invasion, which does not appear to have been reported previously. CASE PRESENTATION: An 81-year-old woman presented with a large swelling on the parietal scalp 12 years after resection of spiradenoma from the same site. The tumor showed intracranial invasion with involvement of the superior sagittal sinus and repeated recurrences after four surgeries with preservation of the sinus. The histopathological diagnosis was eccrine SC. Adjuvant high-precision external beam radiotherapy (EBRT) proved effective after the third surgery, achieving remission of the residual tumor. The patient died 7 years after the first surgery for SC. CONCLUSIONS: Scalp SC with direct intracranial invasion is extremely rare. Radical resection with tumor-free margins is the mainstay of treatment, but the involvement of venous sinuses makes this unfeasible. High-precision EBRT in combination with maximal resection preserving the venous sinuses could be a treatment option for local tumor control.

Advantages of petrosectomy for superficial temporal artery to superior cerebellar artery bypass based on three-dimensional distance measurements using cadaver heads.

Superficial temporal artery (STA) to superior cerebellar artery (SCA) bypass is usually performed via the subtemporal approach (StA), anterior transpetrosal approach (ApA), or combined petrosal approach (CpA), but no study has yet reported a quantitative comparison of the operative field size provided by each approach, and the optimal approach is unclear. The objective of this study is to establish evidence for selecting the approach by using cadaver heads to measure the three-dimensional distances that represent the operative field size for STA-SCA bypass. Ten sides of 10 cadaver heads were used to perform the four approaches: StA, ApA with and without zygomatic arch osteotomy (ApA-ZO- and ApA-ZO+), and CpA. For each approach, the major-axis length and the minor-axis length at the anastomosis site (La-A and Li-A), the major-axis length and the minor-axis length at the brain surface (La-B and Li-B), the depth from the brain surface to the anastomosis site (Dp), and the operating angles of the major axis and the minor axis (OAa and OAi) were measured. Shallower Dp and wider operating angle were obtained in the order CpA, ApA-ZO+, ApA-ZO-, and StA. In all parameters, ApA-ZO- extended the operative field more than StA. ApA-ZO+ extended La-B and OAa more than ApA-ZO-, whereas it did not contribute to Dp and OAi. CpA significantly decreased Dp, and widened OAa and OAi more than ApA-ZO+. ApA and CpA greatly expanded the operative field compared with StA. These results provide criteria for selecting the optimal approach for STA-SCA bypass in light of an individual surgeon's anastomosis skill level.

Challenging direct bypass surgery for very young children with moyamoya disease: technical notes.

Cerebral revascularization for moyamoya disease (MMD) is an effective treatment for improving cerebral ischaemia and preventing rebleeding. Although direct bypass surgery is commonly performed on older children and adults, it is challenging in very young children due to the high difficulty level of the procedure. The subjects were MMD patients under 3 years of age on whom surgery was performed by a single surgeon (Y.A.). Preoperative clinical findings, information related to direct bypass surgery, bypass patency, and the incidence of postoperative stroke were investigated. Combined revascularization, including direct bypass surgery, was performed on 3 MMD patients (3 sides) under 3 years of age. The average diameter of the grafts used in direct bypass was 0.8 mm. The average recipient diameter was 0.8 ± 0.17 (range 0.6-1) mm. In all cases, the anastomotic procedure was completed using 11-0 monofilament nylon thread, and patency was confirmed. Direct bypass for MMD patients under 3 years old is technically challenging. However, despite the anatomical differences between very young children and elderly individuals, direct bypass surgery could certainly be completed. In addition, a rapid recovery from cerebral blood flow insufficiency could yield a promising neurological outcome.

Changes in cerebral blood flow in the postoperative chronic phase after combined cerebral revascularization for moyamoya disease with ischaemic onset.

The purpose of this study was to examine the effects of combined revascularization for ischaemic-onset moyamoya disease (MMD) on cerebral haemodynamics by comparing cerebral blood flow (CBF) during the postoperative chronic phase with preoperative CBF. A retrospective cohort of 24 MMD patients (representing 31 surgeries) who received single photon emission computed tomography (SPECT) before and more than 6 months after surgery was investigated. The CBF value of each vascular territory was extracted from SPECT data, and the value relative to the ipsilateral cerebellar value (relative CBF, or RCBF) was calculated. The correlation between the revascularization effect and the proportional change in RCBF before and after surgery (calculated as post-RCBF/pre-RCBF ("post/pre-RCBF")) was analysed. Furthermore, the relationships between changes in neurological symptoms and post/pre-RCBF were investigated. Preoperative and postoperative mean RCBF values were 0.92 ± 0.15 and 0.96 ± 0.13 (p = 0.619) in the anterior cerebral artery territory, 0.99 ± 0.17 and 1.01 ± 0.17 (p = 0.598) in the middle cerebral artery territory and 1.15 ± 0.22 and 1.14 ± 0.19 (p = 0.062) in the posterior cerebral artery territory, respectively. No significant correlation was found between the revascularization score and post/pre-RCBF. The revascularization score and post/pre-RCBF were not significant predictors of worsening neurological symptoms postoperatively. No significant change in RCBF was observed in any vascular territory in the chronic phase after revascularization. Combined revascularization may assist in the redirection of blood flow from the internal to the external carotid system and contribute to CBF maintenance.

Quick and simple dural threading technique for transsphenoidal surgery - dural tenting, haemostasis and skull base reconstruction.

BACKGROUND: Dural suturing is one of the most robust reconstruction methods in transsphenoidal surgery; however, the technique is considered difficult, primarily due to the restricted range of needle movement. METHOD: We performed dural threading during transsphenoidal surgery by holding the needle with forceps as a hook and moving the needle in a distal to proximal direction. CONCLUSION: Our dural suturing technique is simple and quick. It can be used not only for dural closure but also for other procedures, such as controlling haemostasis from the intercavernous sinus and dural tenting.

Efficacy and safety of the endoscopic "wet-field" technique for removal of supratentorial cavernous malformations.

OBJECTIVE: Cerebral cavernous malformations (CMs) presenting with focal neurological symptoms or mass effects require surgical removal. In recent years, cylindrical retractors have been widely utilized for the removal of deep-seated lesions during both microscopic and endoscopic surgery. In the present study, we evaluated the efficacy and safety of endoscopic transcylinder removal of CMs using a novel wet-field technique. METHODS: We included 13 patients with supratentorial CMs who had undergone endoscopic transcylinder surgery between April 2013 and March 2022. One patient experienced recurrence of the CM and underwent a second endoscopic transcylinder surgery. Therefore, we retrospectively evaluated 14 procedures. The surgical field was continuously irrigated with artificial cerebrospinal fluid to maintain expansion and visualization of the tumor bed. We termed this method as the "wet-field technique." Patient characteristics, symptoms, and pre- and postoperative magnetic resonance imaging results were obtained from medical records. RESULTS: The average maximum CM diameter was 35.3 mm (range: 10-65 mm). Cylinder diameters were 6 mm in eight procedures, 10 mm in four procedures, and 17 mm in one procedure. Wet-field technique was applied in all cases. The endoscope provided a bright field of view even under water. Continuous water irrigation made it easier to observe the entire tumor bed which naturally expanded by water pressure. Gross total resection was achieved in 13 procedures, while subtotal resection was achieved in one procedure. No surgical complications were observed. CONCLUSIONS: The endoscopic transcylinder removal using wet-field technique is safe and effective for the removal of symptomatic intracranial supratentorial CMs.

Impact of the extent of resection on the survival of patients with grade II and III gliomas using awake brain mapping.

PURPOSE: The aim of this study was to assess the effect of the extent of resection (EOR) of tumors on survival in a series of patients with grade II and III gliomas (GII/III-gliomas) who underwent awake brain mapping. METHODS: We retrospectively analyzed 126 patients with GII/III-gliomas in the dominant and non-dominant hemisphere who underwent awake brain surgery at the same institution between December 2012 and May 2020. RESULTS: EOR cut-off values for improved progression-free survival (PFS) were determined by a receiver operator characteristic (ROC) analysis of 5-year PFS. The ROC for EOR showed a cut-off value of ≥ 85.3%. The median PFS rate of patients with GII/III-gliomas in the group with an EOR ≥ 100%, including supratotal resection (n = 47; median survival [MS], not reached), was significantly higher than that in the group with an EOR < 90% (n = 52; MS, 43.1 months; 95% CI 37.7-48.5 months; p = 0.03). In patients with diffuse astrocytomas and anaplastic astrocytomas, the group with EOR ≥ 100%, including supratotal resection (n = 25; MS, not reached), demonstrated a significantly better PFS rate than did the group with an EOR < 100% (n = 45; MS, 35.8 months; 95% CI 19.9-51.6 months; p = 0.03). Supratotal or gross total resection was correlated with better PFS in IDH-mutant type of diffuse astrocytomas and anaplastic astrocytomas (n = 19; MS, not reached vs. n = 35; MS, 40.6 months; 95% CI 22.3-59.0 months; p = 0.02). By contrast, supratotal or gross total resection was not associated with longer PFS rates in patients with IDH-wild type of diffuse astrocytomas and anaplastic astrocytomas. CONCLUSIONS: The present study demonstrates a significant association between tumor EOR and survival in patients with GII/III gliomas. The EOR cut-off value for 5-year PFS was ≥ 85.3%. It is noteworthy that supratotal or gross total resection significantly correlated with better PFS in IDH-mutant type of WHO grade II and III astrocytic tumors. In light of our finding that EOR did not correlate with PFS in patients with aggressive IDH-wild type of diffuse astrocytomas and anaplastic astrocytomas, we suggest treatments that are more intensive will be needed for the control of these tumors.

Surgical outcome and graded prognostic assessment of patients with brain metastasis from adult sarcoma: multi-institutional retrospective study in Japan.

BACKGROUND: Brain metastasis (BM) is an uncommon complication of sarcomas with a poor prognosis. Little information is available about the feasibility and prognostic factors of surgical resection of BM from sarcomas. METHODS: This study involved a retrospective analysis of 22 patients with BM from sarcomas who underwent resection at six institutes in Japan. Prognostic factors were analyzed to develop a graded prognostic assessment (GPA) using the log-rank test and Cox regression analysis. For validation of this GPA, we collected data on 100 surgical cases from 48 published reports. RESULTS: Postoperative Karnofsky Performance Status (KPS) improved in 50% of our patients. Median overall survival (OS) was 21 months. Multivariate analysis showed age and alveolar soft part sarcoma (ASPS) were significant preoperative prognostic factors (P < 0.05). RTOG-RPA classification had no significant prognostic value. We developed a GPA system for OS after resection of BM. A score of 0 was assigned to patients aged 18-29 years with non-ASPS, 2 to patients aged 18-29 years with ASPS or 30-76 years with non-ASPS, and 4 to patients aged 30-76 years with ASPS. Median OS for patients with GPA scores of 0, 2, and 4 were 6.5, 16.0, and 44.0 months, respectively (P = 0.002). The results were validated by the data of 100 cases compiled (P < 0.001). CONCLUSION: Median OS of patients with BM from sarcomas was comparable to that from carcinomas after resection. A new sarcoma-specific GPA may help patients and clinicians to select resection as an option for treatment of BM from sarcomas.

STA-enhanced vascularized galeal flap for revascularization of moyamoya disease: technical report.

BACKGROUND: A variety of revascularization techniques have been reported for the management of moyamoya disease to prevent risks of stroke. STA (superficial temporal artery)-MCA (middle cerebral artery) microanastomosis, single or double bypass, with temporal muscle or galeal onlay graft has been the standard operative procedure. METHOD: Our rationale of revascularization surgery has been a combination of STA-MCA double bypass using the frontal and the parietal branches of STA and transfer of a highly vascularized thick galeal flap with maintained STA vasculature. CONCLUSION: This STA-enhanced vascularized galeal flap graft is extremely effective for revascularization of moyamoya disease.

Next Generation Sequencing-Based Transcriptome Predicts Bevacizumab Efficacy in Combination with Temozolomide in Glioblastoma.

Glioblastoma (GBM), the most common and malignant brain tumor, is classified according to its isocitrate dehydrogenase (IDH) mutation status in the 2016 World Health Organization (WHO) brain tumor classification scheme. The standard treatment for GBM is maximal resection, radiotherapy, and Temozolomide (TMZ). Recently, Bevacizumab (Bev) has been added to basic therapy for newly diagnosed GBM, and monotherapy for recurrent GBM. However, the effect of IDH1 mutation on the combination of Bev and TMZ is unknown. In this study, we performed transcriptomic analysis by RNA sequencing with next generation sequencing (NGS), a newly developed powerful method that enables the quantification of the expression level of genome-wide genes. Extracellular matrix and immune cell migration genes were mainly upregulated whereas cell cycle genes were downregulated in IDH1-mutant U87 cells but not in IDH1-wildtype U87 cells after adding Bev to TMZ. In vitro and in vivo studies were conducted for further investigations to verify these results, and the addition of Bev to TMZ showed a significant antitumor effect only in the IDH1-mutant GBM xenograft model. Further studies of gene expression profiling in IDH1 mutation gliomas using NGS will provide more genetic information and will lead to new treatments for this refractory disease.

Effectiveness of plasma treatment on gastric cancer cells.

BACKGROUND: Treatment of peritoneal carcinomatosis arising from gastric cancer remains a considerable challenge. In recent years, the anticancer effect of nonequilibrium atmospheric pressure plasma (NEAPP) has been reported in several cancer cell lines. Use of NEAPP may develop into a new class of anticancer therapy that augments surgery, chemotherapy, and radiotherapy. METHOD: Gastric cancer cells were assessed for changes in cell morphology and rate of proliferation after treatment with NEAPP-exposed medium (PAM). To explore the functional mechanism, caspase 3/7, annexin V, and uptake of reactive oxygen species (ROS) were evaluated, along with the effect of the ROS scavenger N-acetylcysteine (NAC). RESULTS: PAM treatment for 24 h affected cell morphology, suggestive of induction of apoptosis. PAM cytotoxicity was influenced by the time of exposure to PAM, the type of cell line, and the number of cells seeded. Cells treated with PAM for 2 h demonstrated activated caspase 3/7 and an increased proportion of annexin V-positive cells compared with untreated cells. Additionally, ROS uptake was observed in PAM-treated cells, whereas NAC reduced the cytotoxicity induced by PAM presumably through reduction of ROS uptake. Furthermore, CD44 variant 9, which reportedly leads to glutathione synthesis and suppresses stress signaling of ROS, was overexpressed in PAM-resistant cells. CONCLUSIONS: PAM treatment induced apoptosis of gastric cancer cells through generation and uptake of ROS. Local administration of PAM could develop into an option to treat peritoneal carcinomatosis.

The Potential Role of Preoperative Posterior Cerebral Artery Involvement in Predicting Postoperative Transient Neurological Deficits and Ischemic Stroke After Indirect Revascularization in Patients With Moyamoya Disease.

OBJECTIVE: Transient neurological deficits (TNDs) are known to develop after direct bypass for Moyamoya disease and may be risk factors for subsequent stroke. However, the factors involved in the development of TNDs and stroke after indirect revascularization alone, including their association with subsequent stroke, remain unclear. The purpose of this study was to investigate this issue. METHODS: The subjects of the study were 30 patients with Moyamoya disease who underwent a total of 40 indirect revascularization procedures at our institution. Clinical and radiological data were collected retrospectively. To examine factors associated with the development of postoperative TND/stroke/asymptomatic disease, the clinical characteristics of each group were statistically compared. RESULTS: The mean age at surgery was 7 years (range 1-63). TNDs developed after surgery in 9 out of 40 patients (22.5%). Stroke in the acute postoperative period occurred in 3 patients (7.5%), all of whom experienced cerebral infarctions. Demographic data and preoperative clinical information were not different between the groups. However, posterior cerebral artery involvement on preoperative imaging was significantly associated with the development of TNDs and stroke (P = 0.006). Furthermore, postoperative stroke was associated with unfavorable outcomes (P = 0.025). CONCLUSIONS: Posterior cerebral artery involvement is significantly associated with the occurrence of TNDs. In contrast, TNDs after indirect revascularization have little relationship with the subsequent development of stroke. TNDs usually resolve without new strokes, and a better understanding of this particular pathology could help establish an optimal treatment regimen.

5-Fraction Re-radiosurgery for Progression Following 8-Fraction Radiosurgery of Brain Metastases From Lung Adenocarcinoma: Importance of Gross Tumor Coverage With Biologically Effective Dose ≥80 Gy and Internal Dose Increase.

The criteria for indication of salvage stereotactic radiosurgery (SRS) for local progression following multi-fraction (mf) SRS of brain metastases (BMs) remain controversial, along with the optimal planning scheme. Herein, we described a case of BMs from pan-negative lung adenocarcinoma (LAC), in which the two lesions of local progression following initial eight-fraction (8-fr) SRS were re-treated with 5-fr SRS with the biologically effective dose (BED10) of ≥80 Gy, based on the linear-quadratic (LQ) formula with an alpha/beta ratio of 10. The re-SRS resulted in the alleviation of symptoms and favorable tumor responses with minimal adverse effects during the 7.3-month follow-up. In the lesions of local progression, the gross tumor volume (GTV) coverage with 49.6 Gy (BED10 80 Gy) was generally insufficient, and the GTV dose wes relatively homogeneous with ≥87% isodose covering. In contrast, the 5-fr re-SRS was performed with sufficient GTV coverage with ≤68% isodose of 43 Gy (BED10 80 Gy). Taken together, sufficient GTV coverage with a BED10 of ≥80 Gy and steep dose increase inside the GTV boundary, that is, extremely inhomogeneous GTV dose, are important in 8-fr SRS for ensuring excellent local control of BMs from pan-negative LAC. For local progression following mfSRS that does not fulfill both criteria, re-SRS with the above planning scheme can be an efficacious and safe treatment option for at least six months, especially in cases in which the prior SRS was performed with a dose/fractionation under adequate consideration of brain tolerance. The BED10 seems to be the most suitable for estimating the anti-tumor efficacies of SRS doses in 3-8 fr, similar to that of a single fraction of 24 Gy.

Correlation of Brain Metastasis Shrinking and Deviation During 10-Fraction Stereotactic Radiosurgery With Late Sequela: Suggesting Dose Ramification Between Tumor Eradication and Symptomatic Radionecrosis.

Stereotactic radiosurgery (SRS) with >5 fraction (fr) has been increasingly adopted for brain metastases (BMs), given the current awareness of limited brain tolerance for ≤5 fr. The target volume/configuration change and/or deviation within the cranium during fractionated SRS can be unpredictable and critical uncertainties affecting treatment accuracy, plus the effect of these events on the long-term outcome remains uncertain. Herein, we describe a case of two challenging BMs treated by 10 fr SRS with a unique dose-gradient optimization strategy, in which the large cystic tumor revealed an intriguing correlation of such inter-fractional change with late radiographic sequela, suggesting a dose threshold for attaining long-term local tumor control and being immune to symptomatic brain necrosis. A 63-year-old man presented with two cystic lesions located in the left parietal lobe (19.9 cm3) and pons (1.1 cm3) one month after surgery for esophageal squamous cell carcinoma. The principles for 10 fr SRS were as follows: (1) very inhomogeneous gross tumor volume (GTV) dose covered by 53 Gy, biologically effective dose with an alpha/beta ratio of 10 (BED10) of ≥80 Gy; (2) moderate dose spillage margin outside the GTV boundary: 2-2.5 mm outside the GTV margin was covered by 37 Gy, BED10 of ≈50 Gy; (3) concentrically-laminated, steep dose increase inside the GTV boundary: 2 mm inside the GTV margin was covered by ≥62 Gy, BED10 of ≥100 Gy. At the completion of SRS, the parietal lesion showed significant shrinking and dorsomedial shifting with slight evisceration of the GTV, followed by marked regression of the parietal lesion within four months. At 13.5 months, a cystic change was noted at the dorsal part of the remnant. At 16.7 months, ventral enhancement gradually expanded without enlargement of the dorsal cystic component. On the T2-weighted images, the dorsal low-intensity remnant and ventral iso-intensity blurry-demarcated component were contrasting. Pathological examinations during and after lesionectomy at 17.4 months revealed necrosis only. At 30.5 months, the patient had a left visual field defect without recurrence. In contrast, the pons lesion showed no notable change during 10 fr SRS and nearly complete remission over six months with its sustainment without radiation injury at 30.5 months. Taken together, 10 fr SRS with a sufficient BED10 can provide superior tumor response and safety for BM that is not amenable to ≤5 fr SRS. Although a very inhomogeneous GTV dose can contribute to early and adequate tumor shrinkage and subsequent local tumor eradication, significant tumor shrinkage during fractionated SRS (fSRS) inevitably results in unnecessary higher dose exposure to the surrounding brain, which could lead to late radiation injury requiring intervention. The optimum dose should be determined through further investigation, in consideration of the dynamic and unpredictable nature of the actual absorbed doses to both the tumor and the surrounding brain.

Local Control Failure After Five-Fraction Stereotactic Radiosurgery Alone for Symptomatic Brain Metastasis From Squamous Cell Lung Carcinoma Despite 43 Gy to Gross Tumor Margin With Internal Steep Dose Increase and Tumor Shrinkage During Irradiation.

Five-fraction (fr) stereotactic radiosurgery (SRS) is increasingly being applied to large brain metastases (BMs) >2-3 cm in diameter, for which 30-35 Gy is the commonly prescribed dose. Since 2018, to further enhance both safety and efficacy, we have limited the five-fr SRS to approximately ≤3 cm BMs and adopted our own modified dose prescription and distribution: 43 and 31 Gy cover the boundaries of the gross tumor volume (GTV) and 2 mm outside the GTV, respectively, along with a steep dose increase inside the GTV boundary, that is, an intentionally very inhomogeneous GTV dose. Herein, we describe a case of symptomatic BM treated with five-fr SRS using the above policy, which resulted in a maximum tumor response with nearly complete remission (nCR) followed by gradual tumor regrowth despite obvious tumor shrinkage during irradiation. A 71-year-old man who had previously undergone surgery for squamous cell carcinoma (SCC) of the lungs presented with right-sided hemiparesis attributed to the para-falcine BM (27 mm in maximum diameter, 5.38 cm3). The BM was treated with five-fr SRS, with 99.2% of the GTV covered with 43 Gy and 59% isodose. Neurological symptoms improved during SRS, and obvious tumor shrinkage and mitigation of perilesional edema were observed upon completion of SRS. No subsequent anti-cancer pharmacotherapy was administered due to idiopathic pulmonary fibrosis (IPF). Despite a maximum response with nCR at four months, the tiny residual enhancing lesion gradually enlarged from 7.7 months to 22.7 months without neurological worsening. Although a consistent T1/T2 mismatch suggested the dominance of brain radionecrosis, 11C-methionine positron emission tomography showed increased uptake in the enhancing lesion. Pathological examination after total lesionectomy at 24.6 months revealed viable tumor tissue. Post-SRS administration of nintedanib for IPF may have provided some anti-tumor efficacy for lung SCC and may mitigate the adverse effects of SRS. The present case suggests that even ≥43 Gy with ≤60% isodose to the GTV boundary and ≥31-35 Gy to the 2 mm outside the GTV are insufficient to achieve long-term local tumor control by five-fr SRS alone in some large BM from lung SCC.

Fifteen-Fraction Radiosurgery Followed by Reduced-Dose Whole-Brain Irradiation With a Total Biologically Effective Dose of >90-100 Gy for a Locally Invasive Brain Metastasis From Lung Adenocarcinoma With a High Dissemination Potential.

A deep-seated, locally infiltrative 5.8-cm brain metastasis (BM) involving the ventricular wall and optic radiation is deemed unamenable for a safe total resection, while preventing tumor seeding. Meanwhile, radiotherapeutic management alone for such a BM close to the brainstem is also challenging. We describe such a BM (gross tumor volume [GTV] 40.3 cm3) from lung adenocarcinoma (LAC), located in the left temporo-occipital lobes, with extensive invasion to the tentorium cerebelli and a high potential for dissemination. The BM was treated with 15-fraction(s) (fr) stereotactic radiosurgery (SRS) followed by whole-brain irradiation (WBI) at 27 Gy/15 fr with a 19-day interval. During the SRS, the solid component away from the tentorium showed obvious shrinkage. The cumulative biologically effective doses (BEDs) of the minimum and D99% of the GTV were ≥92.3 Gy and ≥102.6 Gy, respectively, where the BED was based on the linear-quadratic formula at an alpha/beta ratio of 10 (BED10). Despite a maximum response with nearly complete regression at 7.5 months, local tumor regrowth near the tentorial incisura became gradually apparent from 11.2 to 19.3 months. Salvage re-SRS with 53 Gy/10 fr specific to these lesions resulted in obvious regression at 5.8 months. However, radiation injury concomitant with triventriculomegaly progressed from 7.9 to 13.9 months, eventually leading to meningeal dissemination and patient mortality at 34.6 months. This case demonstrates that a BED10 ≥90-100 Gy in 30 fr to the GTV boundary with a more than two-week interval without combined systemic therapy is insufficient for achieving complete local tumor eradication of a 40-cc LAC-BM. Shorter treatment duration with a steeper dose gradient outside and inside the GTV in the SRS or a volumetric modulated arc-based SRS combined with simultaneously integrated WBI may improve efficacy and safety.

Robotic Radiosurgical Boost After Whole-Brain Radiotherapy for 12 Brain Metastases: En Bloc Consecutive Irradiation With Comprehensively Optimized Single Plan for Eight Lesions Totaling 118 cc.

General radiotherapeutic management for >10 brain metastases (BMs) totaling >100 cm3, including multiple large lesions (>10-30 cm3) in close proximity, demonstrated limited efficacy and/or safety. We describe a case of 12 BMs, summating 122.2 cm3, including a 39.6 cm3 maximum lesion and adjacent ones. The patient had an 8.1-year treatment history for recurrent/metastatic breast cancer refractory to endocrine and chemotherapy. BMs were treated with conventional whole-brain radiotherapy (WBRT) with 30 Gy/10 fractions (fr), followed by an immediate stereotactic radiosurgery (SRS) boost with 27 Gy/5 fr (52-64% isodoses) which covers the gross tumor boundaries of selected eight lesions (total 118.4 cm3). The SRS dose was defined to ensure the cumulative biologically effective dose (BED10) of just ≥80 Gy while minimizing the risk of radiation injury. The SRS was performed using a CyberKnife (CK) robotic system (Accuray Incorporated, Sunnyvale, California, United States) with a variable-sized collimator (10-40 mm), for which en bloc consecutive irradiation, using 215 beams based on a comprehensively optimized single plan (path), was adopted. The treatment time per fraction was ≤45 min (mean 5.6 min per lesion). Afterward, BMs demonstrated remarkable regression over six months, causing the total residual visible lesions of 12.6 cm3 (10.3%) at 11.4 months, despite the absence of obvious lesion shrinkage during the radiotherapy. WBRT, followed by an immediate 5-fr SRS boost with a total BED10 of 80 Gy to large and/or culprit lesions, can be an efficacious and safe treatment option for multiple BMs, totaling >120 cm3. En bloc consecutive irradiation with a single path provides overwhelmingly more efficient delivery for treating multiple lesions using CK in terms of irradiation time and comprehensive reduction of normal brain dose compared to individual planning. Volumetric-modulated arc-based >10-fr SRS with simultaneously integrated reduced-dose WBRT may be an alternative to further enhance efficacy and safety.

CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in primary central nervous system lymphoma.

BACKGROUND: Rituximab, high-dose methotrexate (HD-MTX), procarbazine and vincristine (R-MPV), has significantly prolonged the survival of patients with primary central nervous system lymphoma (PCNSL), but predictive factors for response to R-MPV have not yet been investigated. Herein, we investigated the correlation of MYD88 L265P and CD79B Y196 mutations, which are the most frequently found molecular alterations in PCNSL, with prognosis of patients with PCNSL treated with R-MPV. METHODS: We investigated the long-term clinical course and status of MYD88 and CD79B genes in 85 patients with PCNSL treated with R-MPV or HD-MTX treatment, and the correlation of these genetic mutations with prognosis. RESULTS: R-MPV achieved an excellent tumor control rate (61.6% and 69.9% of 5-year progression-free and overall survival rates, respectively). While MYD88 L265P mutation had no significant effect on survival, patients with CD79B Y196 mutations exhibited prolonged survival (p < 0.05). However, the association of CD79B Y196 mutation with a better prognosis was not observed in the HD-MTX cohort, which indicated that CD79B Y196 mutation was a predictive marker for a favorable response to R-MPV. Furthermore, we established an all-in-one rapid genotyping system for these genetic mutations. CONCLUSIONS: In conclusion, CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in PCNSL. The rapid identification of MYD88 L265P and CD79B Y196 mutations can be helpful not only for the accurate molecular diagnosis of PCNSL but also for the prediction of response to R-MPV.

Frameless Co-Registration of Biplane 2D Digital Subtraction Angiography Whole Frames and 3D Rotational Angiography-Based Cone-Beam Computed Tomography Angiogram on Dedicated Software for Stereotactic Radiosurgery of Cranial Vascular Malformations.

PURPOSE: Given its high spatial resolution and vasculature selectivity, the cone-beam computed tomography (CT) angiography (CBCTA) image acquired by selective 3D rotational angiography (3DRA) is the most suitable 3D image for the target definition of stereotactic radiosurgery (SRS) for intracranial arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs). Furthermore, the relatively low temporal resolution of 3DRA-based CBCTA can be complemented by the stereotactic co-registration of orthogonally paired 2D dynamic digital subtraction angiography (2D-DSA). The integration of 2D-DSA, which is usually limited to one or a few frames for each projection, into CBCTA and/or planning CT can be achieved only by catheter-directed angiography on the day of SRS via a dedicated image localizer under rigid frame fixation to the skull, which imposes substantial burdens on patients. This study aimed to demonstrate a novel, convenient, and significantly less invasive method for the frameless co-registration of biplane 2D-DSA whole frames and CBCTA on commercially available dedicated software, namely, Brainlab® Elements (Brainlab AG, Munich, Germany), and present its prerequisite for successful image fusion. Technical Report: Elements have afforded the following functionality: A 3D vasculature image is automatically extracted as a floating image from any 3D image series containing vascular details and then subsequently co-registered manually and automatically to a selected frame pair of 2D-DSA with a six-degree-of-freedom rigid registration. As a preclinical feasibility study, two anonymous image datasets from patients harboring cerebral AVM and transverse-sigmoid (TS) DAVF were used to verify the accuracy and practicality of Elements for the frameless co-registration of 2D/3D vascular images, particularly on the assumption of clinical workflow for the target delineation of SRS planning. The use of ordinary unsubtracted CBCTA resulted in the insufficient extraction of abutting vessels or vessels that are in close proximity to bony structures, particularly in the case of TS-DAVF, where the fistulous pouch and the affected venous sinuses were adjacent to the cranial bone. By contrast, the amount and selectivity of vasculatures and the accuracy of subsequent image fusion were significantly improved from the subtracted CBCTA. The integration of CBCTA into dynamic 2D-DSA allowed the simultaneous review of both image information by sharing any concerning point and 2D or 3D structures under a common 3D coordinate. CONCLUSIONS: Elements enable the clinically useful frameless co-registration of biplane 2D-DSA whole frames into CBCTA, for which the routine acquisition of both subtracted and unsubtracted CBCTA axial images for ordinary diagnostic purposes is an indispensable prerequisite for successful image fusion and further widespread application. This frameless integration of the 2D/3D angiogram would dramatically enhance both the frame-based and frameless SRS workflow and circumstances by allowing users to forward SRS planning well in advance before SRS, along with the omission of invasive angiography on the day of SRS, and would broaden the implementation of frameless SRS. Furthermore, the comprehensive alternating interactive review of the 2D/3D integrated angiogram leads to a more in-depth quasi-4D understanding of the affected angioarchitectures compared with the separate viewing of each image.