Multimodality durable salvage of recurrent brain metastases refractory to LITT, SRS and immunotherapy with resection and cesium-131 brachytherapy: case report and literature review

2021 ◽  
Vol 14 (12) ◽  
pp. e245369
Author(s):  
Kenny Kwok Hei Yu ◽  
Brandon S Imber ◽  
Nelson S Moss
Keyword(s):  
Brain Metastases ◽  
Checkpoint Inhibitor ◽  
Performance Status ◽  
Treatment Options ◽  
Optimal Combination ◽  
Ablation Therapy ◽  
Thermal Ablation Therapy ◽  
Therapy Strategy ◽  
Select Group ◽  
Locally Recurrent

Brain metastases (BrM) are treated with multimodality therapy, however the optimal combination and timing of modalities in the setting of recurrent tumours that have failed prior treatments remain poorly defined. We present a case of a patient with biopsy-confirmed renal cell carcinoma BrM with good performance status initially treated with laser interstitial thermal ablation therapy (LITT) followed by stereotactic radiosurgery and dual checkpoint inhibitor immunotherapy. He subsequently developed rapid in-field recurrence which was treated with salvage surgical resection and implantation of intracavitary cesium-131 brachytherapy. The patient’s disease remained stable through 18 months postoperatively. This case illustrates the range of options available and provides a combination salvage therapy strategy in a select group of locally recurrent patients who have exhausted conventional treatment options.

scholarly journals Melanoma Brain Metastases in the Era of Targeted Therapy and Checkpoint Inhibitor Therapy

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1489
Author(s):  
John M. Rieth ◽  
Umang Swami ◽  
Sarah L. Mott ◽  
Mario Zanaty ◽  
Michael D. Henry ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Treatment Strategies ◽  
Poor Performance Status ◽  
Poor Overall Survival ◽  
Melanoma Brain Metastases

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.

scholarly journals P14.35 The modern management of brain metastases

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii74-iii75
Author(s):  
N D Wallace ◽  
P J Kelly
Keyword(s):  
Decision Making ◽  
Brain Metastases ◽  
Performance Status ◽  
Treatment Options ◽  
Poor Performance ◽  
Best Supportive Care ◽  
Poor Performance Status ◽  
Trade Off ◽  
Cns Penetration ◽  
The Impact

Abstract BACKGROUND Technological and clinical advances have improved outcomes for patients with brain metastases. They have also added significantly to the complexity of decision-making in such cases. We set out to review the roles of different treatment options to guide management for patients with newly-diagnosed brain metastases. MATERIAL AND METHODS We undertook a comprehensive literature review to examine all treatment options for brain metastases. We particularly focused on recent advances and where these can be applied to clinical practice.We examined the impact of the improvement of SRS technology from older frame-based setups to modern linear accelerator based treatment with the capacity for fractionated stereotactic radiotherapy (SRT). We identified clinical situations where either SRS or WBRT, or a combination of the two, should be most strongly considered. Several novel targeted systemic therapies cross the blood-brain-barrier so we have explored their outcomes for patients with brain metastases from BRAF-mutated melanoma and EGFR or ALK/ROS1 mutated NSCLC. By examining these techniques in detail, we have formulated an algorithm-based approach which can inform management. RESULTS Surgery is most beneficial in patients with a reasonable prognosis and where other treatment options are unlikely to provide equivalent control. SRS to the surgical cavity can frequently be used alone for post-operative consolidation. SRS and fractionated SRT are valuable treatment options for increasingly large lesions and for increasing numbers of lesions. The choice between SRS and WBRT is, in many cases, a trade-off between the improved intracranial control of WBRT and the more favourable side effect profile of SRS. Upfront therapy with some systemic agents with CNS penetration is an acceptable approach in carefully-selected patients whose outcome is felt to be more related to their extracranial disease. Best supportive care is preferable for many patients with poor performance status and/or short prognosis, although more aggressive measures have a role in the case of symptomatic lesions. CONCLUSION A multidisciplinary approach involving Neurosurgeons, and both Radiation and Medical Oncologists is needed to fully evaluate the options for individual patients. As many of the treatment decisions are a trade-off between quality of life and outcome metrics, shared decision-making with patients is also critical to ensure that patients receive the best treatment for them.

scholarly journals CMET-25. COMPARATIVE EFFICACY OF TREATMENT PARADIGMS FOR BRAIN METASTASES – A SYSTEMATIC REVIEW

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi56-vi57
Author(s):  
Karanbir Brar ◽  
Yosef Ellenbogen ◽  
Jiawen Deng ◽  
Nebras Warsi ◽  
Alireza Mansouri
Keyword(s):  
Systematic Review ◽  
Brain Metastases ◽  
Primary Tumour ◽  
Performance Status ◽  
Treatment Options ◽  
Egfr Inhibitors ◽  
Open Label ◽  
Serious Adverse Events ◽  
Specific Patient ◽  
Significant Difference

Abstract BACKGROUND Brain metastases (BM) are prevalent in several primary cancers and are the most commonly diagnosed intracranial tumours in adults. The aim of this systematic review was to critically evaluate and compare existing management paradigms for BMs from all primary tumour sites. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, and CENTRAL for randomized controlled trials (RCTs) published until October 2018 and selected comparative RCTS with >50 patients. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). RESULTS A screen of 3188 abstracts yielded 49 RCTs with 8122 patients. The median sample size was 103 (range 39–779). 17/49 RCTs included lung cancer patients, 3/49 breast cancer, 2/49 melanoma, and 27/49 all primary tumour sites. Most studies were phase II/III superiority, open-label, parallel trials. All included patients >18 years of age with at least 1 BM proven on CT/MRI. Most included patients with favorable performance status (KPS >70 or ECOG 0–2). Interventions compared included targeted therapies (e.g. EGFR inhibitors, 7/49), chemotherapeutic regimens (28/49), WBRT (43/49), SRS (12/49), and surgical resection (3/49). A statistically significant difference in OS was reported by 7 studies, and in PFS by 8 studies. Of these, 3 showed improved PFS or OS on addition of temozolomide to WBRT, and 2 showed improved PFS in EGFR-positive patients treated with EGFR inhibitors. The incidence of serious adverse events was not substantially different between treatment arms in most studies. CONCLUSIONS Though the majority of studies did not report a benefit to OS or PFS, temozolomide + WBRT showed a benefit in 3 studies, and improvement in PFS was seen in EGFR-positive patients treated with EGFRi. Given the varying treatment approaches in practice today, these data support the need for a meta-analysis to accurately characterize the efficacy of existing treatment options for specific patient populations.

Immune checkpoint inhibitor use near the end of life.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11533-11533
Author(s):  
Chad Glisch ◽  
Travis Snyders ◽  
Stephanie Gilbertson-White ◽  
Yuya Hagiwara ◽  
Mohammed M. Milhem ◽  
...  
Keyword(s):  
Brain Metastases ◽  
End Of Life ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Chart Review ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Performance Status ◽  
Retrospective Chart Review ◽  
Stage 4

11533 Background: Studies of chemotherapy near the end of life reveal increased costs, adverse effects and minimal clinical benefit. Immune Checkpoint Inhibitor (ICI) use near the end of life has not been described. We studied factors related to ICI use near the end of life. Methods: We conducted a single-institution retrospective chart review of patients who received ICI and died between August 2014 and December 2018. End of life ICI (EOL-ICI) was defined as treatment within the last 30 days of life and comparisons were made to patients who received treatment > 30 days from end of life (non EOL-ICI). Results: 441 patients were reviewed. Mean age was 64 and 182 (41%) were female. 294 (67%) received ICI within the last 90 days of life and 117 (27%) within the last 30 days of life. At time of last ICI, 145 (33%) had brain metastases and 416 (94%) were stage 4. The most common cancers were melanoma (124, 28%), NSCLC (118, 27%) and urothelial carcinoma (34, 8%). The EOL-ICI group had a higher proportion of patients with ECOG ≥3 at time of last treatment (22% vs. 7%, p = < .001), higher rate of death in hospital (32% vs. 18%, p = 0.003) and lower hospice enrollment (52% vs. 76%, p = < .001). The EOL-ICI group received fewer ICI doses (mean 5.1 vs 6.7, p = 0.016). A higher proportion of patients in the EOL-ICI group were just beginning treatment and received ≤ 3 doses (60% vs 40%, p < .001). There was no difference in mean age or presence of brain metastases between the groups. Even when the cutoff for EOL-ICI is extended from 30 to 90 days, there remain significant differences in ECOG, hospice enrollment and starting ICI but no difference in rate of dying in the hospital. Conclusions: One out of four patients studied received ICI within the last 30 days of life. EOL-ICI treatment is associated with higher rates of death in the hospital and lower hospice enrollment. Our results suggest that performance status is important when considering treatment with ICI. Use of ICI in the last 30 days of life had minimal clinical benefit and high cost.

Cabozantinib in combination with atezolizumab in non-small cell lung cancer (NSCLC) patients previously treated with an immune checkpoint inhibitor: Results from cohort 7 of the COSMIC-021 study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9610-9610
Author(s):  
Joel W. Neal ◽  
Farah Louise Lim ◽  
Enriqueta Felip ◽  
Ryan D. Gentzler ◽  
Shiven B. Patel ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Advanced Nsclc ◽  
Immune Cell ◽  
Checkpoint Inhibitor ◽  
Performance Status ◽  
Treatment Options ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Recist 1.1

9610 Background: First-line immunotherapy with/without chemotherapy is standard of care for patients (pts) with advanced NSCLC; however, there is a need for effective treatment options after progression on a prior immune checkpoint inhibitor (ICI). Cabozantinib (C) may augment response to ICI by inhibiting kinases implicated in suppressing immune cell responses and has shown encouraging clinical activity in combination with ICI in other tumor types including RCC and HCC. COSMIC-021, a multicenter phase 1b study, is evaluating the combination of C with atezolizumab (A) in various solid tumors (NCT03170960). We report results from cohort 7 in NSCLC pts after prior ICI therapy. Methods: Eligible pts had ECOG performance status (PS) 0-1 and radiographic progression after one prior anti-PD-1/PD-L1 ICI given alone or in combination with chemotherapy for metastatic non-squamous NSCLC. Up to 2 lines of prior systemic anticancer therapies were permitted. Pts received C 40 mg PO QD and A 1200 mg IV Q3W. CT/MRI scans were performed Q6W for the first year and Q12W thereafter. Primary endpoint is ORR per RECIST 1.1 by investigator. Other endpoints include safety, duration of response (DOR), progression-free survival, and overall survival. Results: Thirty pts with advanced NSCLC were enrolled. Median age was 67 yrs (range 41, 81), 43% were male, 57% had ECOG PS 1, and 23% had liver metastases. Median duration of prior ICI therapy was 4.8 months (mo; range 0.8, 29), and 15 (50%) pts were refractory to prior ICI (progressive disease as best response). As of December 20, 2019, the median follow-up was 8.9 mo (range 5, 20) with 9 (30%) pts continuing study treatment. The most common treatment related adverse events (TRAEs) of any grade were diarrhea (53%), fatigue (37%), nausea (23%), decreased appetite (20%), palmar-plantar erythrodysesthesia (20%) and vomiting (20%). Grade 3/4 TRAEs occurred in 14 (47%) pts, and 1 (3.3%) had grade 5 TRAEs of myocarditis and pneumonitis. Confirmed ORR per RECIST 1.1 was 23% (7 of 30 pts; all partial responses including 3 pts refractory to prior ICI). Time to response was 1.4 mo (range 1, 3), and median DOR was 5.6 mo (range 2.6, 6.9). DCR (CR+PR+SD) was 83%. Conclusions: The combination of C and A had an acceptable safety profile and showed encouraging clinical activity in pts with advanced NSCLC who had progressed after prior ICI therapy. The response rate was greater than previously observed with C monotherapy. Due to the promising data, enrollment in this cohort has been expanded and is ongoing. Clinical trial information: NCT03170960 .

Paeonol Inhibits Prostate Cancer Cell Invasion and Epithelial-Mesenchymal Transformation by Inactivation of STAT3 Pathway

2020 ◽  
Vol 19 (1) ◽  
pp. 15-20
Author(s):  
Junyi Xiang ◽  
Feng Huang ◽  
Renhua Huang ◽  
Jingzhan Su ◽  
Yulong Liu
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Surrogate Marker ◽  
Cytotoxic Agents ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Mesenchymal Transformation ◽  
Dose Dependent

Prostate cancer is one of the leading causes of death in men all over the world. Treatment options such as androgen ablation therapy and cytotoxic agents have many undesirable side effects, narrow therapeutic windows, or other limitations. In this research, we have explored the effects of paeonol on prostate cancer and its mechanism of action. Our results have shown that paeonol reduced the viability of prostate cancer cells in a dose-dependent manner. The wound-healing assay, a surrogate marker of tumor metastasis, showed that the relative wound width of 10 µM group was less than that of 50 µM paeonol-treated cells. Besides, the results of the transwell assay also showed that the number of migrated cells was significantly lower after treatment with 50 µM paeonol compared to the 10 µM group. The Western blot results showed that paeonol treatment induced a decrease in the mesenchymal markers (vimentin and N-cadherin), while the epithelial marker (E-cadherin) increased in a dose-dependent manner suggesting that paeonol effectively inhibits the epithelial-mesenchymal transformation in PC3 cells. Furthermore, the expression of STAT3 and p-STAT3 was also decreased after paeonol treatment, which indicated that the STAT3 signaling pathway was inhibited by paeonol. To conclude, the results summarized in this paper suggest that paeonol could be a potential candidate in the treatment of prostate cancer.

scholarly journals Application of Nanoparticles and Nanomaterials in Thermal Ablation Therapy of Cancer

Nanomaterials ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 1195 ◽  
Author(s):  
Zhannat Ashikbayeva ◽  
Daniele Tosi ◽  
Damir Balmassov ◽  
Emiliano Schena ◽  
Paola Saccomandi ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Thermal Ablation ◽  
Conventional Heating ◽  
Great Promise ◽  
Magnetic Iron Oxide Nanoparticles ◽  
Ablation Therapy ◽  
Treatment Techniques ◽  
Thermal Ablation Therapy ◽  
Heating Capacity ◽  
Tumor Region

Cancer is one of the major health issues with increasing incidence worldwide. In spite of the existing conventional cancer treatment techniques, the cases of cancer diagnosis and death rates are rising year by year. Thus, new approaches are required to advance the traditional ways of cancer therapy. Currently, nanomedicine, employing nanoparticles and nanocomposites, offers great promise and new opportunities to increase the efficacy of cancer treatment in combination with thermal therapy. Nanomaterials can generate and specifically enhance the heating capacity at the tumor region due to optical and magnetic properties. The mentioned unique properties of nanomaterials allow inducing the heat and destroying the cancerous cells. This paper provides an overview of the utilization of nanoparticles and nanomaterials such as magnetic iron oxide nanoparticles, nanorods, nanoshells, nanocomposites, carbon nanotubes, and other nanoparticles in the thermal ablation of tumors, demonstrating their advantages over the conventional heating methods.

scholarly journals Cyberknife® hypofractionated stereotactic radiosurgery (CK-hSRS) as salvage treatment for brain metastases

2021 ◽  
Author(s):  
Sergej Telentschak ◽  
Daniel Ruess ◽  
Stefan Grau ◽  
Roland Goldbrunner ◽  
Niklas von Spreckelsen ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Poor Prognosis ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Salvage Treatment ◽  
Treatment Modalities ◽  
Large Tumor ◽  
Fractionated Radiotherapy ◽  
Hypofractionated Stereotactic Radiosurgery

Abstract Purpose The introduction of hypofractionated stereotactic radiosurgery (hSRS) extended the treatment modalities beyond the well-established single-fraction stereotactic radiosurgery and fractionated radiotherapy. Here, we report the efficacy and side effects of hSRS using Cyberknife® (CK-hSRS) for the treatment of patients with critical brain metastases (BM) and a very poor prognosis. We discuss our experience in light of current literature. Methods All patients who underwent CK-hSRS over 3 years were retrospectively included. We applied a surface dose of 27 Gy in 3 fractions. Rates of local control (LC), systemic progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier method. Treatment-related complications were rated using the Common Terminology Criteria for Adverse Events (CTCAE). Results We analyzed 34 patients with 75 BM. 53% of the patients had a large tumor, tumor location was eloquent in 32%, and deep seated in 15%. 36% of tumors were recurrent after previous irradiation. The median Karnofsky Performance Status was 65%. The actuarial rates of LC at 3, 6, and 12 months were 98%, 98%, and 78.6%, respectively. Three, 6, and 12 months PFS was 38%, 32%, and 15%, and OS was 65%, 47%, and 28%, respectively. Median OS was significantly associated with higher KPS, which was the only significant factor for survival. Complications CTCAE grade 1–3 were observed in 12%. Conclusion Our radiation schedule showed a reasonable treatment effectiveness and tolerance. Representing an optimal salvage treatment for critical BM in patients with a very poor prognosis and clinical performance state, CK-hSRS may close the gap between surgery, stereotactic radiosurgery, conventional radiotherapy, and palliative care.

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