McDermott MW (ed): Radiosurgery, vol. 7

Objective:The therapeutic landscape for localized prostate cancer (PC) is evolving. Stereotactic radiotherapy (SRT) has been reported to be at least not inferior to standard radiotherapy, but the effect of androgen deprivation therapy (ADT) in this setting is still unknown and its use is left to clinical judgment. There is therefore the need to clarify the role of ADT in association with SRT, which is the aim of the present study.Methods:We present a study protocol for a randomized, multi-institutional, Phase III clinical trial, designed to study SRT in unfavorable intermediate and a subclass of high-risk localized PC. Patients (pts) will be randomized 1:1 to SRT + ADT or SRT alone. SRT will consists in 36.25 Gy in 5 fractions, ADT will be a single administration of Triptorelin 22.5 mg concurrent to SRT. Primary end point will be biochemical disease-free survival. Secondary end points will be disease-free survival, freedom from local recurrence, freedom from regional recurrence, freedom from distant metastasis and overall survival (OS); quality of life QoL and patient reported outcomes will be an exploratory end point and will be scored with EPIC-26, EORTC PR 25, IPSS, IIEF questionnaires in SRT + ADT and SRT alone arms. Moreover, clinician reported acute and late toxicity, assessed with CTCAE v. 5.0 scales will be safety end points.Results:Sample size is estimated of 310 pts. For acute toxicity and quality of life results are awaited after 6 months since last patient in, whereas, for efficacy end points and late toxicity mature results will be available 3–5 years after last patient in.Conclusion:Evidence is insufficient to guide decision making concerning ADT administration in the new scenario of prostate ultra-hypofractionation. Hence, the need to investigate the ADT role in SRT specific setting.Advances in knowledge:The stereotactic prostate radiotherapy with or without ADT trial (SPA Trial) has been designed to establish a new standard of care for SRT in localized unfavorable intermediate and a subclass of localized high risk PC.

Long-term Outcome of Gamma Knife Stereotactic Radiosurgery for Multiple Sclerosis Associated Trigeminal Neuralgia

Objective To explore the effect of psychological intervention on anxiety and depression in intracranial neoplasms patients after gamma knife （γ-knife ） radiosurgery .Methods One hundred and sixty intracranial neoplasms patients after γ-knife radiosurgery were chosen and randomly divided into the control group and the observation group , each with 80 cases.The control group received the routine nursing , and the observation group received the psychological intervention on the basis of the routine nursing .The patients were surveyed by the self-rating anxiety scale （ SAS） , self-rating depression scale （ SDS） before and after the γ-knife radiosurgery , and the effect was compared between two groups .Results The cases of patients with moderate and severe depression before the intervention were all 19 cases in two groups , and the cases after the intervention were 17 cases in the control group , and were 10 cases in the observation group , and the difference was statistically significant （Z=3.422,P〈0.01）.The cases of patients with moderate and severe anxiety before the intervention were all 32 cases in two groups , and the cases after the intervention were 31 cases in the control group, and were 4 cases in the observation group , and the difference was statistically significant （ Z=3.702, P〈0.01）.Conclusions Systematic psychological intervention is helpful to relieve the anxiety and depression in the intracranial neoplasms patients after γ-knife radiosurgery , and enhance the confidence and courage of treatment in patients so as to ensure the smooth completion of γ-knife radiosurgery . Key words: Intracranial neoplasms; Gamma knife radiosurgery; Negative psychology; Psychological intervention

Population Based Phase II Trial of Stereotactic Ablative Radiotherapy (SABR) for up to 5 Oligometastases: Preliminary Results of the SABR-5 Trial

The purpose of the systematic review is to summarize the data regarding safety and efficacy of stereotactic body radiation therapy in patients with oligometastases of colorectal cancer to the liver.Published scientific articles on the topic were identified by searching the databases mEDLInE, Pubmed, EmBASE. The review includes publications reporting on the results of treatment of patients undergoing stereotactic radiation therapy for. The systematic review includes all retrospective and prospective studies found over the past 15 years with at least 10 patients with liver metastases of colorectal origin included and standardized methodology of radiation therapy. We included into the review 20 studies comprising 919 patients. Comparative analysis was complicated because of the absence of control groups in all of the studies. moreover, 16 studies were single-center with heterogeneous groups of patients and various regimens of stereotaxic radiation therapy. Despite this, the researchers achieved 60–100 % rates of one-year local control, 56–100 % one-year overall survival with median overall survival up to 45 months and the number of clinically significant complications less than 10 %.From our point of view, the results of published studies support the safety and efficacy of stereotactic radiation therapy in patients with colorectal cancer and oligometastatic liver disease. we consider stereotactic body radiation therapy to be one of the local control options in case of careful patient selection and the use of modern radiation therapy options. further randomized controlled trials are needed.

Gamma Knife radiosurgery (GKR) is a minimally invasive surgical option for drug-resistant essential glossopharyngeal neuralgia (GPN). The authors reviewed pain outcomes and complications in GPN patients who underwent a second or a third GKR for recurrent or persistent pain. A retrospective review of all patients treated in a single center (Marseille, France) since 2004 was performed. Median prescribed dose was 85Gy (range 70-90Gy) at second GKR and 85Gy at third GKR. Clinical outcome was evaluated using the Barrow Neurological Institute (BNI) scale. Six patients (4 males, 2 females) underwent second or third GKR. The median age was 70.2years (range 64-83years) at second GKR and 79.8years at third GKR. No patient had any previous surgery but GKR. Five cases had a neurovascular conflict. Median follow-up period was 12months (range 10-94months) after second GKR and 16months after third GKR. The median delay to initial pain freedom response was 30days (range 3-120days). One patient experienced pharyngeal hypoesthesia after second GKR. After a third GKR, up to 16months, no side effects were encountered. At the last follow-up, 3 patients were BNI I, 2 were BNI IIIa, and one did not have any improvement. Second GKR resulted in pain reduction with low risk of additional morbidity. In patients unsuitable for microvascular decompression, GKR as a repeat or third treatment for intractable GPN is safe and effective. Third GKR was not associated with any side effects up to 16months after the procedure.

Stereotactic Ablative Radiation Therapy (SAbR) Used to Defer Systemic Therapy in Oligometastatic Renal Cell Cancer

Delayed Complications in Patients Surviving at Least 3 Years After Stereotactic Radiosurgery for Brain Metastases

9557 Background: There is growing evidence to suggest synergism between stereotactic ablative radiotherapy (SABR) and immunotherapy (IO) against metastatic melanoma. The optimal timing and dosing of SABR for this purpose has not been established. Here, we report results from a Phase I trial, finding the best outcomes with low dose SABR delivered late. Methods: Metastatic melanoma pts with at least two metastases received SABR to a single metastatic site. All pts had standard dose IO with anti-PD1 and/or anti-CTLA4. Following a standard 3+3 design, pts were escalated through three SABR doses (10Gy, 15Gy and 20Gy) delivered at three different time points (Cycle 1, 2, or 3 of IO). Dose limiting toxicity (DLT) were defined as Grade 3 or higher toxicity within 3 months of first treatment and assessed by an independent data safety monitoring committee (IDSMC). Logistic or cox regressions were used to assess the impact of SABR dose, timing and use of combination IO on toxicity, progression-free (PFS) and overall survival (OS) while controlling age, gender and baseline performance status. Results: Between April 2016 and August 2018, 24 pts were enrolled. The median age was 66 years and most were ECOG 0-1 (92%). The median follow-up was 10 months. Three pts (12.5%) developed DLTs (enterocolitis, hepatitis and liver function derangement). None occurred at SABR treated sites and all were in pts receiving 15Gy. DLTs were not associated with SABR timing (p = 0.44) or use of combination IO (p = 0.72). On this basis the IDSMC recommended stopping the trial and maximum tolerated SABR dose was defined at 10 Gy. The median PFS and OS were respectively 5.4m (95% CI 2.1m-NR) and 16.9m (95% CI 7.1m-NR). The median PFS for those receiving 10Gy was numerically higher than those receiving 15Gy (11.8m vs 2.6 m, p = 0.42). The only treatment related factor associated with improved PFS (HR = 0.14, p = 0.02) and OS (HR = 0.09, p = 0.04) was receiving SABR with Cycle 3. SABR dose (PFS p = 0.75, OS p = 0.67) and IO type (PFS p = 0.13, OS p = 0.06) were not significant. Conclusions: SABR combined with IO is generally safe overall. We found the optimal therapeutic index may be achieved with 10Gy delivered with the third cycle of IO; a strategy that warrants further testing. Clinical trial information: ACTRN12616001064493.

A 24-year-old woman underwent craniotomy for falx meningioma (5 cm in diameter) on October 24, 1995. The deepest part of the tumor was located in the anterior horn of the lateral ventricle, which was not resected. The histology was clear cell meningioma (CCM), aggressive in nature. The MIB-1 labeling index was high (11%). She underwent gamma knife (GK) radiosurgery for the residual tumor with an irradiation dose of 16 Gy at the tumor periphery on May 24, 1996. The postradiosurgical course was uneventful. The residual intraventricular tumor gradually decreased in size, but the peripheral portion gradually grew into the diencephalic region. The patient remained in good condition for 5 years until September 2001, when she exhibited memory disturbance and lethargy. Magnetic resonance imaging demonstrated a large tumor (4.5 cm in diameter) in the diencephalon, compressing the optic nerves and fornix. The calculated tumor doubling time was 120 days. A second craniotomy was performed on October 9, 2001. The tumor was totally resected through the anterior transcallosal approach. The histology and the MIB-1 labeling index of the tissue from the second operation did not differ markedly from those of the first operation. Neither tumor recurrence nor metastasis has been observed to date. GK radiosurgery contributed to control of the residual intraventricular tumor, but the peripheral portion of the tumor, which received a relatively low radiation dose (16 Gy), grew rapidly. This suggests that a marginal dose of 16 Gy may not be sufficient for control of CCM.

This study aims to assess the clinical outcomes of patients with spine metastases who underwent stereotactic ablative radiation therapy (SABR) as part of their treatment. SABR has arisen as a contemporary treatment option for spinal metastasis patients with good prognoses. Between November 2010 and September 2018, Spinal SABR was performed in patients with metastatic disease in different settings: radical (SABR only), postoperative (after decompression and/or fixation surgery), and reirradiation. Local control (LC), pain control, overall survival (OS) and toxicities were reported. Eighty-five patients (corresponding to 96 treatments) with spine metastases were included. The median age was 59 years (range, 23-91). In most SA BR (82.3%, n = 79) was performed as the first local spine treatment, while in 12 settings (12.5%), fixation and/or decompression surgery was performed prior to SABR. Two-year overall survival rate was 74.1%, and median survival was 19 months. The LC rate at 2 years was 72.3%. With regard to pain control, among 67 patients presenting with pain before SA BR, 83.3% had a complete response, 12.1% had a partial response, and 4.6% had progression. Vertebral compression fractures occurred in 10 patients (11.7%), of which 5 cases occurred in the reirradiation setting. Radiculopathy and myelopathy were not observed. No grade III or IV toxicities were seen. This is the first study presenting a Brazilian experience with spinal SA BR, and the results confirm its feasibility and safety. SABR was shown to produce good local and pain control rates with low rates of adverse events.

This study was designed to evaluate hearing preservation after gamma knife radiosurgery (GKRS) and to determine the relation between hearing preservation and cochlear radiation dose in patients with a sporadic vestibular schwannoma (VS). Prospective study involving patients suffering from VS who received GKRS from June 2003 until November 2007. Pure tone and speech audiometry were conducted before and after GKRS. The thresholds at pure tone audiometry were taken as a measure of hearing. Pure tone average (PTA) was defined as the mean threshold at 0.5 kHz, 1.0 kHz, 2.0 kHz, and 4.0 kHz. Hearing was classified according to the 2003 consensus meeting in Tokyo. Stereotactic surgery was performed using a Leksell 4C Gamma Knife (Elekta, Stockholm, Sweden). A total of 69 patients were included in the study. Mean tumor size was 17 mm. Mean marginal dose at the tumor was 11.0 Gy (range, 9.3 Gy-12.3 Gy), mean maximal dose was 19.7 Gy (range, 16 Gy-25.5 Gy). Mean maximal dose at the cochlea was 10.27 Gy (range, 3.1 Gy-16.1 Gy), and mean minimal dose at the cochlea was 2.6 Gy (range, 0.9 Gy-7.4 Gy). Mean PTA before GKRS was 43 dB (standard deviation [SD] 20 dB), mean PTA after GKRS was 63 dB (SD 30 dB). Mean interval between pre-GKRS audiometry and GKRS was 8.0 months. Between GKRS and post-GKRS audiometry, mean interval was 14.2 months. Hearing was considered to be preserved (max +1 class, Tokyo classification) in 52 (75%) of 69 patients. However, only 32 patients had class A, B, or C (serviceable hearing) before GKRS. Within this group, only 13 patients (41%) had a hearing class A, B, or C after GKRS. A significant relation was found between the maximal cochlear dose and the difference in PTA before and after GKRS. Hearing preservation is correlated to the maximal radiation dose at the cochlea. The purpose of developing GKRS techniques was to avoid collateral damage in healthy tissues. This study emphasizes the need for exact radiation planning to reduce the cochlear radiation dose if the hearing is to be preserved. Laryngoscope, 2009.

An International Radiosurgery Consortium Survey for Gynecological Stereotactic Ablative Radiation Therapy

154 Background: Metastatic colorectal cancer is common disease that is treated mainly with systemic chemotherapy with or without target therapy combined with local therapies when feasible. Patients with OM-CRC may benefit from local treatments, classically surgery, but more recently SRT is also showing to be effective. We aimed to access the benefit of SRT in patients (pts) with OM-CRC that where not candidates for surgery. Methods: This retrospective study evaluated all the pts with CRC from a single institution that did SRT for OM-CRC. SRT was done with 3D or IMRT/VMAT planning and daily volumetric image. 1-10 fractions were delivered aiming to keep BED > 100Gy10. Dose was decreased as necessary to respect the constraints and minimize toxicity. Progression free survival (PFS) was analyzed from SRT to first progression or death, ST-free survival (STFS) from SRT to the beginning on next ST line or death. Results: We evaluated 32 consecutive pts from Sep/2014 to Jul/2019. Forty-six courses of SRT where performed. Mean age was 56 ± 13y, 60% female and 65% had colon cancer. 52% had metastatic disease after radical treatment. 63% were off ST by the time of the SRT. SRT treatment sites were lung and liver in 28%, bones and lymph nodes 13%, and CNS 11%. 72% of pts had only 1 treated lesion and 70% did 1 SRT course. Most commonly used regimens were 3 x 10-18Gy (35%), 4 x 10-12Gy (15%) and 5 x 7-10Gy (22%). 37% of treatments had BED≥100Gy10 and 78% were done with IMRT/VMAT. With a median follow-up of 16.1m (IQR 8.2-32.7), the median PFS was 5.4m (95% CI 4.1-11.0) and STFS was 12.7m (95% CI 0.8-24.5). Patients with multiple SRT courses had longer interval between disease progression and starting the next ST line (median 2.2 vs 12.4m). Pts that where on ST holidays before SRT had higher STFS (HR = 0.24 95% CI 0.1-0.6, p = 0.001) probably due to selection bias (lower disease volume). The 3y OS was 71%, median was not reached. Conclusions: Local treatment with SRT for OM-CRC showed to be feasible and safe with promising PFS and OS that deserves further investigation. The median STFS superior to a year suggests that SRT can influence OM-CRC treatment positively, possible impacting quality of life and even treatment costs.

Trigeminal neuralgia (TN) is an excruciating pain that can occur with petroclival meningiomas (PCMs). Gamma knife radiosurgery (GKRS) is an appealing option for small PCMs, but the role of microsurgery (MS) compared to GKRS is not well defined for small PCMs with regard to TN relief. From January 2009 to September 2019, 70 consecutive patients were treated by GKRS or MS for newly diagnosed, small (< 3.5cm) PCMs with TN. GKRS or MS were performed for 35 patients each. The surgical outcome and TN control according to Barrow Neurological Institute (BNI) score were retrospectively analyzed and compared between GKRS and MS. The predominant origin of PCMs was upper clival (49%) with trigeminal nerve compression at the medial dorsal root entry zone. Tumor control rates were equally 94% with GKRS or MS for a mean tumor size and volume of 2.3cm and 5.3cm3, respectively. The preoperative BNI scores were mostly II (40%) and IV (37%) with GKRS and MS, respectively. TN relief without medications (BNI scores I and II) was achieved in 13 of 35 patients (37%) with GKRS and 32 of 35 patients (91%) with MS during a mean follow-up of 50.5months. The most common complications after GKRS and MS were dysesthesia (23%) and diplopia (9%), respectively. MS could be more effective than GKRS in providing prompt, medication-free pain relief from TN for small PCMs. The risks of MS have to be considered carefully in experienced hands, especially for small PCMs.