Non small cell lung cancer intracranial metastases radiosurgery

Non small cell lung cancer intracranial metastases radiosurgery

Multisession radiosurgery (M-GKS) may be an effective alternative for large brain metastases from Non small cell lung cancer (NSCLC). Specifically, severe radiation induced toxicity (≥ grade 3) did not occur in M-GKS for large-volume metastases. Although the long-term effects and results from larger samples remain unclear, M-GKS may be a suitable palliative treatment for preserving neurological function 1).

Traditionally, whole brain radiotherapy (WBRT) has been the cornerstone of Non small cell lung cancer intracranial metastases treatment, but its indication is a matter of debate. A randomized trial has shown that for patients with a poor prognosis, WBRT does not add quality of life (QoL) nor survival over the best supportive care. In recent decades, stereotactic radiosurgery (SRS) has become an attractive non-invasive treatment for patients with BM. Only the BM is irradiated to an ablative dose, sparing healthy brain tissue. Intracranial recurrence rates decrease when WBRT is administered following SRS or resection but does not improve overall survival and comes at the expense of neurocognitive function and QoL. The downside of SRS compared with WBRT is a risk of radionecrosis (RN) and a higher risk of developing new BM during follow-up. Currently, SRS is an established treatment for patients with a maximum of four BM. Several promising strategies are currently being investigated to further improve the indication and outcome of SRS for patients with BM: the effectivity and safety of SRS in patients with more than four BM, combining SRS with systemic therapy such as targeted agents or immunotherapy, shared decision-making with SRS as a treatment option, and individualized isotoxic dose prescription to mitigate the risk of RN and further enhance local control probability of SRS.

The review of Hartgerink et al., discusses the current indications of SRS and future directions of treatment for patients with BM of NSCLC with focus on the value of SRS 2).


Radiosurgery for multiple BMs is controversial, yet patients with EGFR Non small cell lung cancer intracranial metastases and Anaplastic lymphoma kinase non small cell lung cancer may be uniquely suited to benefit from this approach. These results support single and multiple courses of radiosurgery without WBRT for patients with oncogene-addicted NSCLC with four or more BMs 3).

References

1)

Park K, Kim JW, Chung HT, Paek SH, Kim DG. Single-Session versus Multisession Gamma Knife Radiosurgery for Large Brain Metastases from Non-Small Cell Lung Cancer: A Retrospective Analysis. Stereotact Funct Neurosurg. 2019 May 22:1-7. doi: 10.1159/000496154. [Epub ahead of print] PubMed PMID: 31117101.
2)

Hartgerink D, van der Heijden B, De Ruysscher D, Postma A, Ackermans L, Hoeben A, Anten M, Lambin P, Terhaag K, Jochems A, Dekker A, Schoenmaekers J, Hendriks L, Zindler J. Stereotactic Radiosurgery in the Management of Patients With Brain Metastases of Non-Small Cell Lung Cancer: Indications, Decision Tools and Future Directions. Front Oncol. 2018 May 9;8:154. doi: 10.3389/fonc.2018.00154. eCollection 2018. Review. PubMed PMID: 29868476; PubMed Central PMCID: PMC5954030.
3)

Robin TP, Camidge DR, Stuhr K, Nath SK, Breeze RE, Pacheco JM, Liu AK, Gaspar LE, Purcell WT, Doebele RC, Kavanagh BD, Rusthoven CG. Excellent Outcomes with Radiosurgery for Multiple Brain Metastases in ALK and EGFR Driven Non-Small Cell Lung Cancer. J Thorac Oncol. 2018 May;13(5):715-720. doi: 10.1016/j.jtho.2017.12.006. Epub 2017 Dec 19. PubMed PMID: 29269007.

Gamma Knife Radiosurgery for trigeminal neuralgia outcome

Gamma Knife Radiosurgery for trigeminal neuralgia outcome

Significant pain reduction after initial SRS: 80–96% 1) 2) 3) 4) but only ≈ 65% become pain free. Median latency to pain relief: 3 months (range: 1 d-13 months) 5).

Recurrent pain occurs within three years in 10–25%. Patients with TN and multiple sclerosis are less likely to respond to SRS than those without MS. SRS can be repeated, but only after four months following the original procedure.

Favorable prognosticators: higher radiation doses, previously unoperated patient, absence of atypical pain component, normal pre-treatment sensory function 6).

Side effects: Hypesthesia occurred in 20% after initial SRS, and in 32% of those requiring repeat treatment 7) (higher rates associated with higher radiation doses) 8).


Outcome prediction of this modality is very important for proper case selection. The aim of a study was to create artificial neural networks (ANN) to predict the clinical outcomes after gamma knife radiosurgery (GKRS) in patients with TN, based on preoperative clinical factors.

They used the clinical findings of 155 patients who were underwent GKRS (from March 2000 to march 2015) at Iran Gamma Knife center, TehranIran. Univariate analysis was performed for a long list of risk factors, and those with P-Value < 0.2 were used to create back-propagation ANN models to predict pain reduction and hypoesthesia after GKRS. Pain reduction was defined as BNI score 3a or lower and hypoesthesia was defined as BNI score 3 or 4.

Typical trigeminal neuralgia (TTN) (P-Value = 0.018) and age>65 (P-Value = 0.040) were significantly associated with successful pain reduction and three other variables including radiation dosage >85 (P-Value = 0.098), negative history of diabetes mellitus (P-Value = 0.133) and depression (P-Value = 0.190). On the other hand, radio dosage > 85 (P-Value = 0.008) was significantly associated with hypoesthesia, other related risk factors (with p-Value < 0.2), were history of multiple sclerosis (P-Value = 0.106), pain duration more than 10 years before GKRS (P-Value = 0.115), history of depression (P-Value = 0.139), history of percutaneous ablative procedures (P-Value = 0.148) and history of diabetes mellitus (P-Value = 0.169).ANN models could predict pain reduction and hypoesthesia with the accuracy of 84.5% and 91.5% respectively. By mutual elimination of each factor in this model we could also evaluate the contribution of each factor in the predictive performance of ANN.

The findings show that artificial neural networks can predict post operative outcomes in patients who underwent GKRS with a high level of accuracy. Also the contribution of each factor in the prediction of outcomes can be determined using the trained network 9).

Case series

The long-term results in 130 patients who underwent radiosurgery for classical TN and were subsequently monitored through at least 7 years (median = 9.9, range = 7-14.5) of follow-up.

The median age was 66.5 years. A total of 122 patients (93.8%) became pain free (median delay = 15 days) after the radiosurgery procedure (Barrow Neurological Institute, BNI class I-IIIa). The probability of remaining pain free without medication at 3, 5, 7 and 10 years was 77.9, 73.8, 68 and 51.5%, respectively. Fifty-six patients (45.9%) who were initially pain free experienced recurrent pain (median delay = 73.1 months). However, at 10 years, of the initial 130 patients, 67.7% were free of any recurrence requiring new surgery (BNI class I-IIIa). The new hypesthesia rate was 20.8% (median delay of onset = 12 months), and only 1 patient (0.8%) reported very bothersome hypesthesia.

The long-term results were comparable to those from our general series (recently published), and the high probability of long-lasting pain relief and rarity of consequential complications of radiosurgery may suggest it as a first- and/or second-line treatment for classical, drug-resistant TN 10).


Thirty-six consecutive patients with medically intractable TN received a median radiation dose of 45 Gy applied with a single 4-mm isocenter to the affected trigeminal nerve. Follow-up data were obtained by clinical examination and telephone questionnaire. Outcome results were categorized based on the Barrow Neurological Institute (BNI) pain scale with BNI I-III considered to be good outcomes and BNI IV-V considered as treatment failure. BNI facial numbness score was used to assess treatment complications.

The incidence of early pain relief was high (80.5 %) and relief was noted in an average of 1.6 months after treatment. At minimum follow-up of 3 years, 67 % were pain free (BNI I) and 75 % had good treatment outcome. At a mean last follow-up of 69 months, 32 % were free from any pain and 63 % were free from severe pain. Bothersome posttreatment facial numbness was reported in 11 % of the patients. A statistically significant correlation was found between age and recurrence of any pain with age >70 predicting a more favorable outcome after radiosurgery.

The success rate of GKRS for treatment of medically intractable TN declines over time with 32 % reporting ideal outcome and 63 % reporting good outcome. Patients older than age 70 are good candidates for radiosurgery. This data should help in setting realistic expectations for weighing the various available treatment options 11).


From 1994 to 2009, 40 consecutive patients with typical, intractable TN received GKRS. Among these, 22 patients were followed for >60 months. The mean maximum radiation dose was 77.1 Gy (65.2-83.6 Gy), and the 4 mm collimator was used to target the radiation to the root entry zone.

The mean age was 61.5 years (25-84 years). The mean follow-up period was 92.2 months (60-144 months). According to the pain intensity scale in the last follow-up, 6 cases were grades I-II (pain-free with or without medication; 27.3%) and 7 cases were grade IV-V (<50% pain relief with medication or no pain relief; 31.8%). There was 1 case (facial dysesthesia) with post-operative complications (4.54%).

The long-term results of GKRS for TN are not as satisfactory as those of microvascular decompression and other conventional modalities, but GKRS is a safe, effective and minimally invasive technique which might be considered a first-line therapy for a limited group of patients for whom a more invasive kind of treatment is unsuitable 12).


Kondziolka et al., evaluated pain relief and treatment morbidity after trigeminal neuralgia radiosurgery.

All evaluable patients (n = 106) had medically or surgically refractory trigeminal neuralgia. A single 4-mm isocenter of radiation was focused on the proximal trigeminal nerve just anterior to the pons. For follow-up an independent physician who was unaware of treatment parameters contacted all patients.

After radiosurgery, 64 patients (60%) became free of pain and required no medical therapy (excellent result), 18 (17%) had a 50% to 90% reduction (good result) in pain severity or frequency (some still used medications), and 9 (9%) had slight improvement. At last follow-up (median, 18 months; range, 6-48 months), 77% of patients maintained significant relief (good plus excellent results). Only 6 (10%) of 64 patients who initially attained complete relief had some recurrent pain. Radiosurgery dose (70-90 Gy), age, surgical history, or facial sensory loss did not correlate with pain relief. Poorer results were found in patients with multiple sclerosis. Twelve patients developed new or increased facial paresthesias after radiosurgery (10%). No patient developed anesthesia dolorosa. There was no other procedural morbidity.

Gamma knife radiosurgery is a minimally invasive technique to treat trigeminal neuralgia. It is associated with a low risk of facial paresthesias, an approximate 80% rate of significant pain relief, and a low recurrence rate in patients who initially attain complete relief. Longer-term evaluations are warranted 13).

References

1)

Brisman R. Gamma knife surgery with a dose fo 75 to 76.8 Gray for trigeminal neuralgia. J Neurosurg. 2004; 100:848–854
2) , 8)

Pollock BE, Phuong LK, Foote RL, Sta ord SL, Gor- man DA. High-dose trigeminal neuralgia radiosur- gery associated with increased risk of trigeminal nerve dysfunction. Neurosurgery. 2001; 49:58–62; discussion 62-4
3)

Kondziolka D, Lunsford LD, Flickinger JC. Stereotactic radiosurgery for the treatment of trigeminal neuralgia. Clin J Pain. 2002; 18:42–47
4)

Massager N, Lorenzoni J, Devriendt D, Desmedt F, Brotchi J, Levivier M. Gamma knife surgery for idi- opathic trigeminal neuralgia performed using a far-anterior cisternal target and a high dose of radiation. J Neurosurg. 2004; 100:597–605
5) , 7)

Urgosik D, Liscak R, Novotny J, Jr, Vymazal J, Vlady- 1982 ka V. Treatment of essential trigeminal neuralgia with gamma knife surgery.JNeurosurg.2005; 102 Suppl:29–33
6)

Maesawa S, Salame C, Flickinger JC, Pirris S, Kond- ziolka D, Lunsford LD. Clinical outcomes after ster- eotactic radiosurgery for idiopathic trigeminal neuralgia. J Neurosurg. 2001; 94:14–20
9)

Ertiaei A, Ataeinezhad Z, Bitaraf M, Sheikhrezaei A, Saberi H. Application of an artificial neural network model for early outcome prediction of gamma knife radiosurgery in patients with trigeminal neuralgia and determining the relative importance of risk factors. Clin Neurol Neurosurg. 2019 Feb 12;179:47-52. doi: 10.1016/j.clineuro.2018.11.007. [Epub ahead of print] PubMed PMID: 30825722.
10)

Régis J, Tuleasca C, Resseguier N, Carron R, Donnet A, Yomo S, Gaudart J, Levivier M. The Very Long-Term Outcome of Radiosurgery for Classical Trigeminal Neuralgia. Stereotact Funct Neurosurg. 2016;94(1):24-32. doi: 10.1159/000443529. Epub 2016 Feb 17. PubMed PMID: 26882097.
11)

Karam SD, Tai A, Wooster M, Rashid A, Chen R, Baig N, Jay A, Harter KW, Randolph-Jackson P, Omogbehin A, Aulisi EF, Jacobson J. Trigeminal neuralgia treatment outcomes following Gamma Knife radiosurgery with a minimum 3-year follow-up. J Radiat Oncol. 2014;3:125-130. Epub 2013 Nov 20. PubMed PMID: 24955219; PubMed Central PMCID: PMC4052001.
12)

Lee JK, Choi HJ, Ko HC, Choi SK, Lim YJ. Long term outcomes of gamma knife radiosurgery for typical trigeminal neuralgia-minimum 5-year follow-up. J Korean Neurosurg Soc. 2012 May;51(5):276-80. doi: 10.3340/jkns.2012.51.5.276. Epub 2012 May 31. PubMed PMID: 22792424; PubMed Central PMCID: PMC3393862.
13)

Kondziolka D, Perez B, Flickinger JC, Habeck M, Lunsford LD. Gamma knife radiosurgery for trigeminal neuralgia: results and expectations. Arch Neurol. 1998 Dec;55(12):1524-9. PubMed PMID: 9865796.
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